Mast Cell Activation Syndrome: current understanding and research needs.

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities which have gained increased attention from patients and medical providers. While several descriptive publications about MCAS exist, there are many gaps in knowledge resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell (MC) activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to MC activation in MCAS patients remain to be elucidated. The purpose of this manuscript is to summarize the known literature, identify gaps in knowledge, and highlight research needs. Several topics are covered: 1) Contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; 2) Mechanistic research; 3) Management of typical and refractory symptoms, and 4) MCAS-specific education for patients and healthcare providers.

Perceptions of patient disease burden and management approaches in systemic mastocytosis: Results of the TouchStone Healthcare Provider Survey.

BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by the KIT D816V mutation and has a broad range of debilitating symptoms. In this study, the authors evaluated SM disease perceptions and management strategies among US health care providers (HCPs). METHODS: Hematologist/oncologist (H/O) HCPs and allergist/immunologist (A/I) HCPs who were treating four or more patients with SM completed an online, 51-item TouchStone HCP Survey, which queried provider characteristics, perceptions of disease burden, and current management. Descriptive analyses by specialty and SM subtype were performed. RESULTS: Of 304 HCPs contacted, 111 (37%) met eligibility criteria, including 51% A/I specialists and 49% H/O specialists. On average, the HCPs had 14 years of practice experience and cared for 20 patients with SM. A/I HCPs saw more patients with nonadvanced SM (78%) compared with H/O HCPs, who saw similar proportions of patients with nonadvanced SM (54%) and advanced SM (46%). HCPs reported testing 75% of patients for the KIT D816V mutation and found an estimated prevalence of 47%. On average, HCPs estimated 8 months between symptom onset and SM diagnosis. HCPs reported that 62% of patients with indolent SM felt depressed or discouraged because of symptoms. In terms of treatment goals for SM, both types of specialists prioritized symptom improvement for nonadvanced SM and improved survival for advanced SM while also prioritizing improving patient quality of life. CONCLUSIONS: Both A/I and H/O specialists highlighted unmet needs for patients with SM. The HCPs surveyed reported a lower rate of KIT D816V mutations and a perceived shorter time between symptom onset and SM diagnosis compared with published estimates. LAY SUMMARY: Specialists treating systemic mastocytosis (SM) completed a 51-item questionnaire about their clinical practices and perceptions of disease impact. The study included 111 hematology, oncology, allergy, and immunology physicians. Physicians reported that most patients had nonadvanced disease, yet SM symptoms significantly disrupted their patients' lives. Physicians estimated that SM is diagnosed within months of symptom onset, in contrast with published reports of years' long delays reported by patients with SM. This study identified unmet needs that can inform educational and patient management priorities in this rare disease.

Patient-reported outcomes among patients with systemic mastocytosis in routine clinical practice: Results of the TouchStone SM Patient Survey.

BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool. METHODS: US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics. RESULTS: Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms. CONCLUSIONS: Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity. LAY SUMMARY: The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM.

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond.

BACKGROUND: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. OBJECTIVE: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients' quality of life by addressing unmet needs. METHODS: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. RESULTS: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. CONCLUSIONS: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.

The Mastocytosis Society Survey on Mast Cell Disorders: Part 2-Patient Clinical Experiences and Beyond.

BACKGROUND: Mast cell diseases such as mastocytosis and mast cell activation syndrome involve abnormal proliferation and/or activation of these cells, leading to many clinically relevant symptoms. OBJECTIVE: To determine the characteristics and experiences of people known or suspected to have a mast cell disorder, The Mastocytosis Society, a US-based patient advocacy, research, and education organization, conducted a survey of patients. METHODS: This Web-based survey was publicized through specialty clinics and the society's newsletter, Web site, and online blogs. Both online and paper copies of the questionnaire were provided together with required statements of consent. RESULTS: The first set of results from this survey of 420 respondents has been previously published; the second set is presented in this article. These results include source(s) of diagnosis, clinical and laboratory tests reported, comorbidities, dietary practices, possible familial occurrence of mast cell disorders, and perceptions concerning mast cell disorder-related medical care needs in the United States. CONCLUSIONS: These patient survey results are provided to assist medical professionals in learning patients' perceptions of their experiences and to give patients with mast cell disorders and caregivers the opportunity to compare experiences with those of other affected individuals.

Patient Perceptions in Mast Cell Disorders.

Understanding experiences, perceptions, and perspectives of patients with a mast cell disorder (MCD), including cutaneous mastocytosis, systemic mastocytosis, mast cell activation syndromes, and hereditary α-tryptasemia, is an important aspect of successful care, treatment, and informed development of novel therapies. This article reviews existing studies and presents new data on MCD patient perceptions regarding medical care, symptoms, allergies/sensitivities, triggers, future health/disease progression, treatment, impact on daily living, quality of life, support needs, and concerns regarding possible familial disease. Discussion includes aspects affecting the MCD community that require further consideration and development.

The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions.

BACKGROUND: Mast cell diseases include mastocytosis and mast cell activation syndromes, some of which have been shown to involve clonal defects in mast cells that result in abnormal cellular proliferation or activation. Numerous clinical studies of mastocytosis have been published, but no population-based comprehensive surveys of patients in the United States have been identified. Few mast cell disease specialty centers exist in the United States, and awareness of these mast cell disorders is limited among nonspecialists. Accordingly, information concerning the experiences of the overall estimated population of these patients has been lacking. OBJECTIVE: To identify the experiences and perceptions of patients with mastocytosis, mast cell activation syndromes, and related disorders, The Mastocytosis Society (TMS), a US based patient advocacy, research, and education organization, conducted a survey of its members and other people known or suspected to be part of this patient population. METHODS: A Web-based survey was publicized through clinics that treat these patients and through TMS's newsletter, Web site, and online blogs. Both online and paper copies of the questionnaire were provided, together with required statements of consent. RESULTS: The first results are presented for 420 patients. These results include demographics, diagnoses, symptoms, allergies, provoking factors of mast cell symptoms, and disease impact. CONCLUSION: Patients with mastocytosis and mast cell activation syndromes have provided clinical specialists, collaborators, and other patients with information to enable them to explore and deepen their understanding of the experiences and perceptions of people coping with these disorders.