Inflammatory marker testing in primary care in the year before Hodgkin lymphoma diagnosis: a UK population-based case–control study in patients aged ≤50 years

Background Proinflammatory conditions are associated with increased risk of Hodgkin lymphoma, although the neoplastic process per se often induces an inflammatory response. Aim To examine pre-diagnostic inflammatory marker test use to identify changes that may define a ‘diagnostic window’ for potential earlier diagnosis. Design and setting This was a matched case–control study in UK primary care using Clinical Practice Research Datalink data (2002–2016). Method Primary care inflammatory marker test use and related findings were analysed in 839 Hodgkin lymphoma patients and 5035 controls in the year pre-diagnosis. Poisson regression models were used to calculate monthly testing rates to examine changes over time in test use. Longitudinal trends in test results and the presence/absence of ‘red-flag’ symptoms were examined. Results In patients with Hodgkin lymphoma, 70.8% (594/839) had an inflammatory marker test in the year pre-diagnosis versus 16.2% (816/5035) of controls (odds ratio 13.7, 95% CI = 11.4 to 16.5, P<0.001). The rate of inflammatory marker testing and mean levels of certain inflammatory marker results increased progressively during the year pre-diagnosis in Hodgkin lymphoma patients while remaining stable in controls. Among patients with Hodgkin lymphoma with a pre-diagnostic test, two-thirds (69.5%, 413/594) had an abnormal result and, among these, 42.6% (176/413) had no other ‘red-flag’ presenting symptom/sign. Conclusion Increases in inflammatory marker requests and abnormal results occur in many patients with Hodgkin lymphoma several months pre-diagnosis, suggesting this period should be excluded in aetiological studies examining inflammation in Hodgkin lymphoma development, and that a diagnostic time window of appreciable length exists in many patients with Hodgkin lymphoma, many of whom have no other red-flag features.