The Mastocytosis Society (Tms) Mast Cell Activation Syndrome (Mcas)

THE MASTOCYTOSIS SOCIETY (TMS) MAST CELL ACTIVATION SYNDROME (MCAS) PATIENT PERCEPTIONS SURVEY aSusan V Jennings, PhD, aValerie M Slee , RN, BSN, aJan B Hempstead, RN, aAndrew M Slee ,PhD, bMariana C Castells, MD, PhD, FAAAAI, cCem Akin, MD, PhD, FAAAAI, dAngela S Bowman, PhD aThe Mastocytosis Society, Inc., USA; bMastocytosis Center, Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; cDepartment of Internal Medicine, d Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, MI, USA; Department of Health and Human Performance, Middle Tennessee State University, Murfreesboro, TN, USA www.TMSforaCure.org

ABSTRACT RESULTS Symptoms Figure 5. Food Restriction Affecting MCAS-Diagnosed Respondents (% of Figure 7. How Often Symptoms of MCAS Interrupt Daily Life of MCAS- Rationale: Mast cell activation syndrome (MCAS) has been increasingly diagnosed. In Respondents) Diagnosed Respondents (% of Respondents) preparation for a National Institutes of Health workshop, The Mastocytosis Society, Inc. Demographics Figure 2. Symptoms Moderately/Severely Affecting 60% or More MCAS-Diagnosed Cannot eat any foods/can tolerate (TMS) conducted a large-scale survey to characterize this population. Very frequently (e.g., daily) 67.7% elemental formula by mouth or tube 1.7% Methods: Upon IRB approval, patient/caregiver-reported (medical records not  Valid responders: N = 1702 Respondents (%) 89.9% 41.3% can eat reviewed) data (N=1702) were collected through an online Qualtrics survey platform, Can safely eat 1-5 foods 10.9% Often (e.g., 1-2x/week) 21.2%  Age: range, 0 – 85 y (M = 43.0, SD = 16.2) 20 foods or less August 17-25, 2018, from those reporting physician-diagnosed MCAS (n=1574) and/or Fatigue 51.3% 35.4% * Can safely eat 6-20 foods 28.7% Occasionally (e.g., 1-2x/month) 7.9% hereditary α-tryptasemia (n=61). Data gathered included demographics, diagnoses/  Gender: Female 87.8% Male 11.5% Blood pressure changes 27.3% 38.8% Can safely eat 21 or more foods, but 71.2% are food- comorbidities, diagnostic criteria, symptoms, quality of life (QoL), and perceptions of  Care received in US: 82.1% (Total: 1702) Light-headedness/fainting 22.8% 38.9% General 29.9% Rarely (e.g., 1-2x/year) 2.5% research and care. still food-restricted restricted Intolerance: multiple chemicals/medications 52.0% 29.4% Never Results: Participants’ ages ranged from 0-85 (M=43.0, SD=16.2), 87.8% female; 82.1% * Only avoid a few food triggers 22.3% 0.5% Hay fever/environmental allergy 32.7% 38.9% Total: 1574 received MCAS treatment in the US. Most commonly reported co-occurring conditions 0% 10% 20% 30% 40% 50% 60% 70% 80% Itching 29.1% 39.8% Not restricted in food types 6.4% were dysautonomia (47.5%) and connective-tissue disorder(s) (41.0%). Of respondents Diagnoses Skin reporting an MCAS diagnosis, 21.5% reported no rise in mast cell mediators, while Flushing 35.3% 40.5%  Respondents reporting being given a diagnosis of MCAS by a physician: 92.5% (1574/1702) * Total: 1574 0% 5% 10% 15% 20% 25% 30% 35% 24.8% reported elevated baseline serum tryptase, 26.0% N-methylhistamine, and Abdominal pain 41.2% 35.7% 21.8% prostaglandins. Most used H1 blockers (91.9%), H2 blockers (71.5%), and/or mast * CONCLUSIONS Diarrhea 29.5% 31.7% -cell stabilizers (55.9%). Moderate/severe symptoms affecting multiple body systems GI  Diagnoses of only MCAS (of options provided), and of MCAS with EDS/connective tissue were wide ranging: 45.5% moderately/severely affected by anaphylaxis, 69.4% food- Bloating 32.1% 36.0% Medications Table I. Additional and Comorbid Diagnoses (given by a physician) disorder and POTS/dysautonomia, were reported by similar proportions of respondents restricted, and 40.1% able to eat ≤20 foods. Symptoms impacted QoL, with 87.6% Intolerance to multiple foods 52.9% 25.5% * Figure 6. Percent of MCAS-Diagnosed Respondents Taking Medications and (~30% each) reporting moderate/severe life interruption; 66.1% reporting daily interruption, 84.7% Yes, n (% of 1574 with Additional Diagnoses (by a physician) Yes, n (% of 1702) Brain fog/cognitive difficulties 39.3% 38.8% moderately/severely affected by unpredictability of onset, and 48.1% often/very MCAS diagnosis) * Percent Reporting Improvement of Symptoms  Elevations of serum tryptase at baseline, n-methyl histamine/histamine, prostaglandins Nasal congestion/itching 23.3% 40.8% frequently requiring assistance with routine care needs. 68.0% reported fair/poor Cutaneous Mastocytosis 163 (9.6) 135 (8.6) and “not yet demonstrated a rise in mediators” were reported by somewhat similar health, with M=17.9 (SD=10.6) poor physical health, M=11.8 (SD=10.2) poor mental Muscle pain and/or stiffness 34.6% 40.2% % Currently Taking (graphed) (% Reporting Improvement of MCAS Symptoms) Systemic Mastocytosis 250 (14.7) 216 (13.7) proportions of respondents (~20 –25% each) health, and M=15.1 (SD=10.9) activity-limited days in the past month. Joint pain 32.9% 40.4% H1 antihistamine Conclusions: Survey data presents a profile of reported MCAS as more chronically Hereditary α-Tryptasemia 60 (3.5) 52 (3.3) 92.5% (76.4%)  Most commonly reported symptoms were fatigue, intolerance to multiple chemicals/ disabling than has been widely recognized, with patients in need of improved, more Severely Moderately 0% 20% 40% 60% 80% medications, intolerance to multiple foods, brain fog/cognitive difficulties, flushing and EDS/Related Connective Tissue H2 antihistamine 72.8% (72.7%) readily available care. 697 (41.0) 657 (41.7) Disorder abdominal pain Symptoms affecting respondents over course of illness with MCAS (“not at all”, “mildly”, Leukotriene inhibitor 39.4% (65.6%)  46.2% are moderately or severely affected by anaphylaxis Dysautonomia/POTS 809 (47.5) 774 (49.2) “moderately”, “severely”); GI, Gastrointestinal; *Moderate + Severe >75%; Total: 1574 Mast cell stabilizer 57.9% (80.1%) INTRODUCTION  29.0% go into anaphylaxis 3 or more times/year (6.2%, 1 or more time(s)/week) Comorbid Diagnoses (by a physician)- % of 1702 Survey Yes, n (% of 1574 with Mast cell diseases (MCD) involve abnormal proliferation, accumulation, function Yes, n Aspirin 10.6% (62.9%) and/or activation of mast cells (MCs). MC activation can occur by both IgE-dependent partial list Population MCAS diagnosis)  41.3% can eat 20 foods or less Steroid and independent mechanisms, causing the release of mediators including histamine, Figure 3. Severity of Anaphylaxis Affecting MCAS-Diagnosed Respondents (% of 15.0% (85.2%)  MCAS only* 455 26.7 28.9 A majority find anti-mediator or mast cell stabilizer therapy helpful in treating symptoms tryptase, arachidonic acid metabolites (such as prostaglandins and leukotrienes), Respondents) Total: 1574 0% 20% 40% 60% 80% 100%  MCAS has a significant impact on quality of life cytokines and chemokines. These mediators can initiate or exacerbate symptoms, MCAS + EDS/Related 120 7.1 7.6 leaving patients with MCD at increased risk for anaphylaxis and chronic and debilitating MCAS + POTS 217 12.7 13.8 “Are you currently taking ______directed at treating your MCAS symptoms?” No answer, 1.2% symptoms. MCAS + EDS/Related + POTS 439 25.8 27.9 Severely, Primary, secondary and idiopathic MC activation syndromes (MCAS) have been 20.6%  Taking or have taken Omalizumab: 17.2% (60.9% report Improvement of MCAS Acknowledgements and Funding The authors thank all survey respondents and those who 1-3 * Of diagnosis options to select, only MCAS was reported described, where patients experience inappropriate MC activation. Clonal MC carrying Symptoms); Total: 1574 helped with publicity. This work was conducted through volunteer efforts, with scientific and D816V or other KIT tyrosine kinase mutations have been identified in patients with Not at all, medical questions resolved by those with relevant background and expertise. SV Jennings, primary MCD, including mastocytosis and (mono)clonal MCAS.1, 2, 4 Specific criteria are 27.1% VM Slee, JB Hempstead and AM Slee have received travel support from The Mastocytosis required to meet a diagnosis of MCAS, and patients with mastocytosis may meet the Quality of Life 2 Society (TMS). MC Castells has received a grant from TMS; has served as a consultant for criteria for both mastocytosis and MCAS. Hereditary α-tryptasemia is a more recently Mediator Testing described entity in which multiplications of the α-tryptase gene have been identified, Table II. Quality of Life and General Health of MCAS-Diagnosed Sanofi, Merck, Lytix Biopharma and Genentech, and is an editor for Annals of Allergy and and this genetic variant has been associated with connective tissue disorders, Respondents Asthma. C Akin has served as a consultant for Blueprint Medicines and Novartis. AS Bowman Figure 1. Percent of MCAS-Diagnosed Respondents Reporting Elevated Mediators Moderately, dysautonomia and mast cell activation-like symptoms; however, this genetic variant has % of MCAS-Diagnosed has no relevant conflicts of interest. also been found in 4-6% of the general population.5 In addition, Postural Tachycardia 25.6% Mildly, Syndrome (POTS) and Ehlers-Danlos Syndrome (EDS) have been described clinically in Respondents Serum tryptase (baseline) 24.8% 25.5% REFERENCES patients with symptoms of MCAS, although underlying involvement of mast cell Total: 1574 Symptoms of MCAS Interrupt Daily Life : 6 1. Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. activation has not been demonstrated biochemically. HOW OFTEN (see Fig. 7) “Very Frequently” or “Often” 88.9% In recent years, mast cell activation syndrome has been increasingly diagnosed,7 and Serum tryptase (after event)† 12.6% J Allergy Clin Immunol. 2010 Dec;126(6):1099-104 e4. HOW MUCH “Extremely” or “Moderately” 88.2% confusion in both medical and patient/caregiver communities has resulted, in part, from 2. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria Figure 4. Frequency of Anaphylaxis Requiring Injectable Epinephrine Affecting MCAS- and global classification of mast cell disorders with special reference to mast cell activation the use of differing diagnostic criteria. In order to initiate a broad discussion into the N-methylhistamine/histamine* 26.0% UNPREDICTABILITY of Symptom Onset Interrupts Daily Life: syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-25. topic, the National Institutes of Health hosted an MCAS workshop in September 2018. Diagnosed Respondents (% of Respondents) “Extremely” or “Moderately” 85.3% 3. Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017 Aug;140(2):349-55. The Mastocytosis Society, Inc. (TMS) was invited to present on Patient Perceptions in Require Assistance for: MCAS. In preparation for the workshop, TMS conducted an MCAS Patient Survey, which 11 β-prostaglandin F2α* 13.2% 4. Valent P, Akin C, Escribano L, Fodinger M, Hartmann K, Brockow K, et al. Standards and “ROUTINE CARE NEEDS” “Very Frequently” or “Often” 49.0% standardization in mastocytosis: consensus statements on diagnostics, treatment has allowed for visualization of the collective experiences and perspectives of the MCAS- 21.8% 1-2x/week or more 6.2% “PERSONAL CARE NEEDS” “Very Frequently” or “Often” 22.0% recommendations and response criteria. Eur J Clin Invest. 2007 Jun;37(6):435-53. diagnosed patient population. Prostaglandin D2* 16.0% General Health: 5. Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, et al. Elevated basal serum tryptase 1-3x/month 8.3% 3 or more/year identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat “Poor” or “Fair” 67.8% METHODS Leukotriene E4* 8.3% (29.0%) Genet. 2016 Dec;48(12):1564-9. For 10 or More of the Past 30 Days:  Anonymous, consent-required, patient/caregiver-reported, IRB-approved, online 3-11x/year 14.5% 6. Bonamichi-Santos R, Yoshimi-Kanamori K, Giavina-Bianchi P, Aun MV. Association of PHYSICAL HEALTH WAS NOT GOOD 73.2% survey conducted using Qualtrics survey development and analysis tools Not yet demonstrated mediator rise 21.5% Postural Tachycardia Syndrome and Ehlers-Danlos Syndrome with Mast Cell Activation  Eligible participants were patients (any age/location) with physician-diagnosed MCAS (Mean = 17.7/30 Days) Disorders. Immunol Allergy Clin North Am. 2018 Aug;38(3):497-504. 1-2x/year or less and/or hereditary α-tryptasemia, with caregivers collaborating in response for 27.3% MENTAL HEALTH WAS NOT GOOD 51.3% Other mediators 18.4% (Mean = 11.9/30 Days) minors Poster content was presented at the 2019 American Academy of Allergy, Asthma and Never 43.3% USUAL ACTIVITIES LIMITED BY PHYSICAL/MENTAL HEALTH 63.6%  Publicized through TMS (Website, Facebook, Inspire, email list), Ehlers-Danlos Total: 1574 Immunology Annual Meeting, San Francisco, CA, USA. Society; encouraged sharing on other mast cell disease-related online forums 0% 5% 10% 15% 20% 25% 30% (Mean = 14.9/30 Days) Jennings SV, Slee VM, Hempstead JB, Slee AM, Castells MC, Akin C, Bowman AS. The Mastocytosis Society † Total: 1574  Posted online through TMS Website link, August 17-25, 2018 After anaphylaxis/MC activation event; -*24 hour or spot urine; “Select all that apply” 0% 10% 20% 30% 40% 50% Options: Very frequently (e.g., daily), Often (e.g., 1-2x/week), Occasionally (e.g., 1-2x/ Mast Cell Activation Syndrome Patient Perceptions Survey. J Allergy Clin Immunol. 2019;143(2):AB427  Valid responders defined as having responded to the diagnosis question and by month), Rarely (e.g., 1-2x/year); Extremely, Moderately, Minimally, Not at all; Poor, Fair, pattern analyses such as random response selection and missingness Good, Very good, Excellent; Total: 1574 Copyright ©, The Mastocytosis Society, Inc., 2019. All rights reserved.