Steroid prescribing in primary care increases prior to Hodgkin lymphoma diagnosis: A UK nationwide case-control study

Background: Steroid use is associated with increased risk of Hodgkin lymphoma (HL). However, allergic symptoms commonly treated with steroids are also presenting features of HL in some patients, thereby introducing protopathic bias in estimates of aetiological associations. It is therefore important to examine steroid prescribing patterns pre-diagnosis to understand timing of associations and when healthcare use increases before cancer diagnosis to inform future epidemiological study design. Methods: We analysed steroid prescribing in 1232 HL patients and 7392 matched controls using primary care electronic health records (Clinical Practice Research Datalink (CPRD), 1987–2016). Using Poisson regression, we calculated monthly steroid prescribing rates for the 24-months preceding HL diagnosis, identifying the inflection point when they start to increase from baseline in cases, comparing rates with synchronous controls, and stratifying by route-of-administration and allergic disease status. Results: 46 % of HL patients had a steroid prescription in the 24-months preceding diagnosis compared to 26 % of controls (OR 2.55, 95 %CI 2.25–2.89, p < 0.001). Odds of underlying HL were greatest in patients receiving multiple steroid prescriptions, oral steroids and in patients with a new allergic disease diagnosis. Among HL patients, steroid prescribing rates increased progressively from 7-months pre-diagnosis, doubling from 52 to 111 prescriptions/1000 patients/month. Conclusion: Steroid prescribing increases during periods leading up to HL diagnosis, suggesting steroid-treated symptoms may be early presenting features of HL. A diagnostic window of appreciable length exists for potential earlier HL diagnosis in some patients; this 7-month ‘lag-period’ pre-diagnosis should be excluded in studies examining aetiological associations between steroids and HL.