Primary Raynaud’s phenomenon is associated with attention deficit hyperactivity disorder: a cohort study harnessing electronic healthcare records

Raynaud’s phenomenon (RP) and attention deficit hyperactivity disorder (ADHD) are common conditions in the general population. Furthermore, RP has been reported to potentially occur, and with severe ischaemic sequelae, in patients treated with ADHD-related medications. We aimed to estimate the risk of ADHD in individuals with phenotypical ‘primary’ (idiopathic) RP. Ours was a cohort study using data from North American electronic healthcare organization records. We defined RP using ≥2 ICD (I73.0) codes, excluding systemic autoimmune rheumatic diseases (akin to PRP). Comparators had ≥2 irritable bowel syndrome ICD (K58) codes (selected with similar epidemiology to RP). Cohorts were stratified by age (<45 and ≥45 years). Our primary outcome was incident ADHD. Time to event analyses were conducted using 1:1 propensity score matched Cox proportional hazard models. We performed 1:1 propensity score matching using relevant covariates separately within predefined age strata, including ADHD-relevant and cardiovascular medications. Among 32,516 (<45 years) and 61,408 (≥45 years) matched pairs, RP was associated with a higher incidence of ADHD in individuals aged ≥45 years (HR 1.251, 95% CI 1.097–1.426), whereas evidence in those aged <45 years was weaker and did not reach conventional statistical significance (HR 1.088, 95% CI 0.996–1.189). In conclusion, RP was associated with an increased risk of incident ADHD, including accounting for known implicated ADHD-related medications, although estimates under <45 years lack precision. Future research is warranted to confirm and explore these observations, including potentially shared pathobiological mechanisms, including small fibre neuropathy, between PRP and ADHD.