Seasonal variation in chronic and acute pain in patients with sickle cell disease

Abstract Introduction: Pain events are the most common symptom of sickle cell disease (SCD) and many patients with SCD also develop chronic pain. Pain events are thought to be due to vasoocclusion, while chronic pain is multifactorial. The effect of seasonal variation on pain is often discussed by patients, but little research has truly explored this notion in depth. A few studies have demonstrated that the incidence of acute vasoocclusion and acute chest syndrome (ACS) are highest in the winter. One study found that colder seasons were associated with significantly increased daily pain intensity. No studies have reported the effect of seasons on chronic pain in SCD. We sought to investigate the effect of seasons on daily pain intensity, pain impact, and pain bothersomeness, and further whether this effect differs between patients with SCD and chronic pain vs those without chronic pain. Methods: Data was extracted from the IMPROVE 1 trial, a single-site prospective study of patients with sickle cell anemia (SCA) (genotypes SS and SB0) who reported cough or wheeze without a diagnosis of asthma. Patients were over the age of 15. Exclusion criteria were incarceration, pregnancy, admission to hospital within 7 days of the study, or more than 15 emergency departments per year . Patients completed daily pain diaries to capture pain severity, pain interference, and pain bothersomeness 10-point Likert scale over 16-weeks. Chronic pain was defined as pain on >50% of days over three months. Quarter 1 is January-March, quarter 2 is April-June, quarter 3 is July-September, and quarter 4 is October to December. ANOVA stratified by chronic pain status was used to determine if pain scores differed between quarters. Results: Of 52 patients initially consented and randomized, 44 patients who turned in daily pain journals were included in this analysis (Total Group). 52% of patients were male and 65% were treated with hydroxyurea. 36 patients had at least 3 months of pain data, 18 patients had pain on most days (Chronic Pain) and 18 patients did not have pain on most days (No Chronic Pain). For all patients evaluated, pain was 2.08, 1.24, 2.41, and 2.64 for quartiles 1,2,3, and 4 respectively (p<0.001). For all patients, pain impact was 1.44, 0.7, 1.33, and 1.59 for quartiles 1, 2, 3, and 4 respectively (p<0.001). For all patients, pain bothersome scores were 1.64, 0.85, 1.38, and 1.74 for quartiles 1,2,3 and 4 (p=0.001). For patients with chronic pain, total pain was 3.47, 3.00, 3.83, and 3.67 in quartiles 1,2,3, and 4 respectively (p=0.027). Pain interference was 2.47, 1.71, 2.09, and 2.19 for quartile 1,2,3, and 4 respectively(p=0.18). Pain bothersomeness was 2.82, 2.06, 2.02, and 2.39 for quartiles 1,2,3 and 4 respectively (p=0.0062). For those without chronic pain scores were 0.47, 0.53, 0.79, and 0.29 in quartiles 1,2,3, and 4 respectively (p=0.29). Pain interference was rated at 0.39, 0.27, 0.51, and 0.26 for quartiles 1,2,3, and 4 respectively (p=0.91). Pain bothersomeness was 0.42, 0.34, 0.66, and 0.25 for quartiles 1,2,3 and 4(p=0.921). Conclusion: For all patients evaluated in this study, pain severity, impact, and bothersomeness appeared to be lowest in quarter 2 (Apr-Jun) and highest in quarter 4 (Oct-Dec). However, when patients were stratified by the presence of chronic pain, those without chronic pain showed no difference in pain quality experienced between quarters while those with chronic pain appeared to have the lowest pain severity in quarter 2, lowest pain bothersomeness in quarters 2 and 3, and no difference in pain interference was seen. We posit that perhaps the differences seen in earlier studies were driven by individuals with chronic pain. As seasons may impact pain experience, individuals with SCA should have access to adequate heating and cooling and more work should be done to evaluate this further.