Incidence and Prevalence of Mastocytosis in Adults: A Danish Nationwide Register Study

Abstract

Introduction: Mastocytosis is a heterogeneous chronic disease caused by a mutation in the cKIT gene that allows for uncontrolled proliferation, accumulation and activation of abnormal mast cells. Mastocytosis is divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM) in which abnormal mast cells are found in various tissues of the body. SM is further divided into the following five subtypes related to disease severity: indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL). Mastocytosis is considered a rare disease with an incidence and prevalence previously found to be 0,89 per 100.000 and 9,59 per 100.000, respectively; however, recent improvements related to diagnostic methods could have led to an increased incidence and prevalence. Therefore, updated data is needed. Methods: This study is a retrospective nationwide register study including all adult (≥18 years) patients with mastocytosis in Denmark diagnosed between January 1 st 1997 and December 31 st 2021. The study was conducted using the Danish Civil Registration System to merge data from the National Patient Register (NPR), the Danish Pathology Register (DPR) and the Danish Cancer Register (DCR). The National Patient Register contain information on all inpatient and outpatient contacts and is considered complete as of 1995-2018. The Danish Pathology Register contain information about all biopsies and pathologic examinations in Denmark and is considered complete as of 1997 to 2021. The Danish Cancer Register contain information on all incidences of cancer in Denmark and is considered complete as of 1987-2021. Year of diagnosis was considered as the earliest date across all registers and patients were categorized as most severe subtype of mastocytosis. The registers did not allow for a categorization of SSM and therefore indolent mastocytosis were all categorized as ISM. Patients without a positive extracutaneous biopsy and who have never been examined with a bone marrow biopsy were classified as mastocytosis in the skin (MIS). Results: These data are the preliminary results of this study. 1627 patient were included (female 924, 56,8%). Mastocytosis in the skin was the most prevalent type of mastocytosis (774, 47,57%), followed by ISM (441, 27,11%), CM (222, 13,64%) and SM-AHN (179, 11%), More than 80% of patients with ASM had another hematologic neoplasm and were categorized as SM-AHN. Few patients were classified as ASM (4, 0,25%) and MCL (7, 0,43%). A positive bone marrow biopsy was found among 601 (36,94%) of the patients; however, 774 (47,57%) patients with mastocytosis were not examined with a bone marrow biopsy. The incidence rate of mastocytosis (all subtypes) was lowest in 2003 with an incidence of 0,74 per 100.000. Hereafter, the incidence increased until reaching the highest level in 2018 with an incidence of 2,77 per 100.000 (figure 1). The 25-year limited-duration prevalence as of 1 st January 2022 was 28,44 per 100.000. Conclusion: This nationwide register study provides updated data on the prevalence and incidence of mastocytosis in Denmark. The incidence rate was found to have an increasing trend until 2018 when it reached the highest value of 2,77 per 100.000. The prevalence was found to be 28,44 and thereby higher than previous studies have found. However, the true prevalence is potentially higher as the data for the years 2019-2021 solely relies on the pathology register. This is preliminary data, and the results will be updated when the NPR is complete for these years.Further analysis will be conducted using the Register of Laboratory Results for Research to evaluate blood tests regarding tryptase levels as well as to provide further information regarding KIT mutational status.