Use of the Rema Score to Distinguish Individuals with Systemic Mastocytosis From Those with Hereditary Alpha-tryptasemia

Authors

  • Maggie Jiang, MD Division of Clinical Immunology and Allergy, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada
  • Peter Vadas, MD, PhD, FRCPC, FACP Division of Clinical Immunology and Allergy, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

DOI:

https://doi.org/10.58931/cait.2025.5179

Abstract

Background: Systemic mastocytosis (SM) and hereditary alpha-tryptasemia (HαT) may present with overlapping clinical manifestations of mast cell activation, making them difficult to distinguish on clinical grounds. Diagnosing SM requires a bone marrow or tissue biopsy whereas HαT can be diagnosed with a buccal swab for genetic testing. Another potential method to differentiate SM from HαT is through a validated scoring system. For example, the Spanish Network on Mastocytosis, Red Española de Mastocitosis (REMA) score has been validated as a predictor of mast cell clonality in SM by using basal serum tryptase levels, clinical symptoms, and sex. This study aims to determine whether REMA scores can differentiate sufficiently between individuals with SM and HαT, thereby confidently ruling in or out the need for more invasive investigations such as bone marrow or tissue biopsy.

Methods: A retrospective chart review was conducted on 39 patients with SM and 24 patients with HαT to calculate their individual REMA scores. A two-sample Wilcoxon test was conducted to assess the difference in median REMA scores between patients with SM and those with HαT. Within the SM cohort, subgroup analysis was performed to compare REMA scores based on the KIT D816V mutation and SM subtype. The area under the curve was calculated to evaluate the discriminatory property of the REMA score.

Results: The Median REMA score within the SM cohort was 2 (0.50, 4.00) compared to -1 (-1.50 0.00) within the HαT cohort (p <0.001). REMA scores in patients with SM did not differ based on the KIT mutation status. A REMA score cut-off of 0.5 was able to distinguish SM and HαT with a specificity of 83.3% (67%,96%).

Conclusion: This novel comparison of REMA scores in patients with SM and HαT highlights a potential role for the calculated REMA score in informing decisions about the need for invasive testing for patients presenting with symptoms of mast cell activation. However, larger comparative studies are needed before incorporating REMA scoring into routine care.

Author Biographies

Maggie Jiang, MD, Division of Clinical Immunology and Allergy, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

Dr. Maggie Jiang is an Allergy and Immunology specialist with comprehensive training from St. Michael’s Hospital and The Hospital for Sick Children (SickKids) in Toronto. She completed medical school at Queen’s University, and residency and fellowship at the University of Toronto. She has a broad interest in all areas of allergy and immunology, including food, environmental, and drug allergies, as well as urticaria, angioedema, allergy immunotherapy, and anaphylaxis. Dr. Jiang is dedicated to providing personalized care to patients of all ages, helping them manage and overcome their allergic/immunologic conditions.

Peter Vadas, MD, PhD, FRCPC, FACP, Division of Clinical Immunology and Allergy, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

Dr. Peter Vadas is Head of the Division of Allergy and Clinical Immunology at St. Michael’s Hospital, Medical Director of the Regional Anaphylaxis Clinic, and Associate Professor of Medicine at the University of Toronto. He is Past President of the Anaphylaxis Foundation of Canada, Past Chair of the Anaphylaxis Committee of the American Academy of Allergy, Asthma and Immunology and Past Head, Section of Anaphylaxis, and Adverse Reactions of the Canadian Society of Allergy and Clinical Immunology. He serves on the executive of the Allergy Asthma and Immunology Society of Ontario.  He had served for over 10 years on the Scientific Advisory Council of the National Peanut Board. Dr. Vadas was an examiner in Allergy and Clinical Immunology for the Royal College of Physicians and Surgeons of Canada and served as head of the Section of Allergy and Clinical Immunology of the Ontario Medical Association. He has published more than 160 peer-reviewed papers and over 20 books and book chapters on allergies and anaphylaxis, including peer‑reviewed articles in Nature, Journal of the American Medical Association and the New England Journal of Medicine. His areas of research include risk factors for severe anaphylaxis, systemic mastocytosis and the roles of platelet activating factor and platelet activating factor acetylhydrolase in severe and fatal anaphylaxis. His recent publication Reproducibility of Symptom Sequences Across Episodes of Recurrent Anaphylaxis was noted as one of the 10 most influential publications of 2022.

References

Khoury P, Lyons JJ. Mast cell activation in the context of elevated basal serum tryptase: genetics and presentations. Curr Allergy Asthma Rep. 2019;19(12):55. doi:10.1007/s11882-019-0887-x

Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med. 1987;316(26):1622-1626.

Caughey GH. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol. 2006;117(6):1411-1414. doi:10.1016/j.jaci.2006.02.026

Carrigan C, Milner JD, Lyons JJ, Vadas P. Usefulness of testing for hereditary alpha tryptasemia in symptomatic patients with elevated tryptase. J Allergy Clin Immunol Pract. 2020;8(6):2066-2067. doi:10.1016/j.jaip.2020.01.012

Fellinger C, Hemmer W, Wöhrl S, Sesztak-Greinecker G, Jarisch R, Wantke F. Clinical characteristics and risk profile of patients with elevated baseline serum tryptase Allergol Immunopathol (Madr). 2014;42(6):544-552. doi:10.1016/j.aller.2014.05.002.

Valent P, Akin C, Bonadonna P, Hartmann K, Brockow K, Niedoszytko M, et al. Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome. J Allergy Clin Immunol Pract. 2019;7(4):1125-1133.e1. doi:10.1016/j.jaip.2019.01.006

Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, et al. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016;48(12):1564-1569. doi:10.1038/ng.3696

Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129(11):1420-1427. doi:10.1182/blood-2016-09-731893

Alvarez-Twose I, Gonzalez-de-Olano D, Sánchez-Muñoz L, Matito A, Jara-Acevedo M, Teodosio C, et al. Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms. Int Arch Allergy Immunol. 2012;157(3):275-280. doi:10.1159/000329856

Horny HP, Metcalf DD, Bennett JM, et al. Mastocytosis. In: WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al (Eds), Lyon IARC Press, Lyon 2008. P.54.

Norris D, Stone J. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Geneva: WHO. 2008:22-23.

R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. [cited March 10, 2025]. Available from: https://www.R-project.org/.

RStudio Team (2020). RStudio: Integrated Development for R. RStudio, PBC, Boston, MA [cited March 10, 2025]. Available from: https://www.rstudio.com/.

Greiner G, Sprinzl B, Górska A, Ratzinger F, Gurbisz M, Witzeneder N, et al. Hereditary alpha tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Blood. 2021;137(2):238-247. doi:10.1182/blood.2020006157.

Lyons JJ, Chovanec J, O’Connell MP, Liu Y, Šelb J, Zanotti R, et al. Heritable risk for severe anaphylaxis associated with increased α-tryptase–encoding germline copy number at TPSAB1. Allergy Clin Immunol. 2021;147(2):622-632. doi:10.1016/j.jaci.2020.06.035

Downloads

Published

2025-06-02

How to Cite

1.
Jiang M, Vadas P. Use of the Rema Score to Distinguish Individuals with Systemic Mastocytosis From Those with Hereditary Alpha-tryptasemia. Can Allergy Immunol Today [Internet]. 2025 Jun. 2 [cited 2025 Jun. 7];5(1):18–26. Available from: https://canadianallergyandimmunologytoday.com/article/view/5-1-Jiang_et_al

Issue

Volume 5, Issue 1, Spring 2025

Section

Articles