(BSPOT35) Leverage of an EHR Database to Estimate Prevalence and Incidence of Lymphatic Malformations (a Rare Disease) in the UK

Background: Lymphatic malformations (LyM) are a rare and serious disease, characterized by fluid-filled cysts likely caused by abnormal development of the lymphatic system. LyM may cause disability, disfigurement, and lifetime morbidity. While rare disease databases estimate LyM prevalence as 1-5 per 10,000, no methods are described.

Objectives: We estimated LyM complete prevalence (number of ever previously diagnosed persons alive at a set time point regardless of cure status) in all ages and incidence in children (most LyM are diagnosed in childhood) during data capture. Since the direct estimate of complete prevalence would not capture LyM cases diagnosed before data capture, we also used annual incidence in children to extrapolate complete prevalence of LyM in the United Kingdom (UK).

Methods: We completed a retrospective analysis of electronic health records (EHR) in the UK using the Clinical Practice Research Datalink (CPRD).
A LyM diagnosis was defined as the presence of a lymphangioma or cystic hygroma encounter in CPRD. We estimated complete prevalence among patients of all ages who were registered to a practice on Jun 30, 2022. We estimated mean annual incidence rate (person years [PY]) and average age of diagnosis of LyM among patients aged 0-17 years between Jan 1, 2000 and Dec 31, 2021. Finally, by using the mean annual incidence rate of LyM in children, we extrapolated complete prevalence of LyM in the UK with the following formula = ([Incidence in children in CPRD] × [Proportion of UK aged 0-17 years] / [Proportion of LyM first diagnosed in childhood]) × ([Life expectancy at birth] - [Average age at LyM diagnosis]).

Results: Among patients of all ages who were registered to a practice on Jun 30, 2022 (N=3,023,573), 577 patients had a LyM diagnosis since start of data capture (Jan 1, 2000). Direct estimate of complete prevalence was 1.91 per 10,000 persons.

Among children observable on Jan 1 of each year from 2000-2021 (17,067,803 PY), there were 354 incident cases of LyM with average age of diagnosis 7 years. The mean annual incidence rate was 0.21 per 10,000 PY.

To account for patients that may have been diagnosed before Jan 1, 2000, we used the mean annual incidence of LyM in children to extrapolate complete prevalence of LyM in the UK: 3.38 per 10,000 persons.

Conclusions: Our direct complete prevalence estimate among patients diagnosed during data capture likely underestimated all patients alive with LyM. Therefore, our capture of annual incidence rates in children was used to calculate a more comprehensive complete prevalence of LyM in the UK. Both complete prevalence estimates fell in line with estimates provided by rare disease databases. For rare diseases diagnosed in childhood, an EHR database with a lifespan lookback period would be useful for complete prevalence estimates.