Background: Sickle cell disease (SCD) is characterized by pain, typically, acute in onset with a subset of events which require hospitalization for treatment with opioid analgesics. A proportion of adults also experience nearly daily pain that appears to share features with chronic pain in other diseases. However, the prevalence of chronic SCD pain in adults is largely undefined. Furthermore, the relationship between chronic pain in SCD and mortality has not been evaluated despite the known association between frequent acute pain crises and increased risk of death. The American Pain Society Pain Taxonomy working group on SCD has recently proposed core diagnostic criteria for chronic pain, although these criteria were not based upon population based data.

Methods: Two hundred thirty five adults were questioned about the presence of chronic pain defined as pain present on more than 50% of days for more than 6 months. This was performed as part of an outpatient evaluation at 2 different clinical sites that included a history, exam and lab studies while patients were in steady state. Subjects enrolled on this study were then followed for up to 5.7 years to evaluate survival by Kaplan Meier analysis.

Results: Forty-nine (21%) met the chronic pain definition. Mean age was 31.1 versus 32.1 years, respectively, and there was no sex difference between groups. Characteristics distinguishing the chronic pain group from all others were a higher body mass index (BMI; P=0.007), more hospitalizations for SCD pain over the past year (mean 6.6 hospitalizations for the chronic pain group; P< 0.0001), a higher number of moderate pain days (i.e. missing work; mean of 66.3 days; P< 0.0001), avascular necrosis in 49% of chronic pain patients (odds ratio 2.53 compared to all others; 95% confidence interval 1.33 to 4.85; P=0.006) and a higher prevalence of any current opioid use (90% versus 69%, P=0.003). In men, priapism was more prevalent for those with chronic pain (71% versus 46% respectively; odds ratio 2.80; 95% confidence interval 1.07 to 7.34; P=0.04). Systolic and diastolic blood pressure were also higher with chronic pain, but these were not quite statistically significant (P=0.06 for both). Overall, the proportion of subjects with both chronic pain and any contributory disease complications defined by the Pain Taxonomy working group (like leg ulcers or avascular necrosis) was 57% (28 out of 49), even though leg ulcers by themselves were not associated with chronic pain (P=0.52). Direct bilirubin was also higher and approached significance (P=0.053), but no other lab studies were associated with chronic pain. Multivariable logistic regressions showed that the number of hospitalizations for pain during the 12 months prior to evaluation (P=2.14 x 10-6), current opioid use (P=0.02) and higher systolic blood pressure (P=0.007) were independent markers associated with chronic pain. Finally, the chronic pain group was not at increased risk of death (Hazard Ratio 1.26; 95% CI 0.24 - 6.63; P=0.79) in a Kaplan Meier survival analysis with a median follow-up of 1.4 years for 174 subjects.

Conclusion: Our definition for chronic pain is consistent with the Pain Taxonomy working group criteria for SCD chronic pain, which was proposed after the initiation of this study. Chronic pain in SCD is characterized by clinical features like frequent hospitalizations, opioid use and vascular manifestations including relative systolic hypertension. Importantly, chronic pain by itself does not appear to be associated with mortality. Larger patient cohorts are needed to confirm these findings and define appropriate chronic pain management for these high risk patients.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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