Temporal Trends in the Incidence of Hemophagocytic Lymphohistiocytosis: A Nationwide Cohort Study From England 2003-2018

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018. We calculated incidence rates of diagnosed HLH per million population by calendar year, age group, sex, and associated comorbidity (hematological malignancy, inflammatory rheumatological or bowel diseases [IBD]). We modeled trends in incidence and the interactions between calendar year, age, and associated comorbidity using Poisson regression. There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (incidence rate ratio [IRR] 2018 compared to 2003: 3.88, 95% confidence interval [CI] 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11, 95% CI 1.09 to 1.12). There was a transition across age groups with greater increases in those aged 5-14 years of HLH associated with rheumatological disease/IBD compared with hematological malignancy, with similar increases in HLH associated with both comorbidities for those 15-54, and greater increases in HLH associated with hematological malignancies for those 55 years and older. The incidence of HLH in England has quadrupled between 2003 and 2018. Substantial variation in the incidence occurred with inflammatory rheumatological diseases/IBD-associated HLH increasing more among the younger age groups, whereas in older age groups, the largest increase was seen with hematological malignancy-associated HLH.

Figure 1.

Venn diagram to show the overlap between of comorbidities within the whole HLH cohort. HLH = hemophagocytic lymphohistiocytosis; IBD = inflammatory bowel disease.

Figure 2.

Incidence (95% CI) of HLH per million population over calendar time (2003–2018) and by age group. CI = confidence interval; HLH = hemophagocytic lymphohistiocytosis.

Figure 3.

Incidence (95% CI) of HLH per million population over calendar time by associated comorbidity. CI = confidence interval; HLH = hemophagocytic lymphohistiocytosis.

Figure 4.

Incidence (LOESS) of HLH per million population over calendar time by age group and comorbidity. HLH = hemophagocytic lymphohistiocytosis; IBD = inflammatory bowel disease.