An Empirical Classification of Chronic Pain Subgroups in Pediatric Sickle Cell Disease: A Cluster-Analytic Approach
Authors: Sil Soumitri , Manikowski Alison , Schneider Mallory , Cohen Lindsey L , Dampier Carlton D. 
Published: November 2021

Abstract
Introduction: Youth with sickle cell disease (SCD) and chronic pain are a heterogeneous group with variability in their daily pain experience and physical and psychosocial functioning. We aimed to 1) empirically derive chronic pain subgroups based on sensory pain characteristics using cluster analysis within a sample of youth with chronic SCD pain, and 2) investigate derived subgroups for differences in sociodemographics, clinical characteristics, and psychosocial and functional outcomes. We hypothesized that chronic SCD pain subgroups with higher sensory pain experiences would be associated with poorer functional and psychosocial outcomes.
Methods: Children and adolescents receiving care at comprehensive SCD clinics at three tertiary care locations within a southeast children's hospital were included if they were aged 10-18 years, any SCD genotype, reported chronic pain (i.e., pain on most days per month for a duration of at least 3 months), and had English fluency. Youth were excluded if they had comorbid medical conditions typically associated with pain but unrelated to SCD or had significant cognitive or developmental limitations that would interfere with study procedures. Patients completed a battery of patient-reported outcomes including pain characteristics (i.e., intensity, frequency, and the Adolescent Pediatric Pain Tool to assess number of pain locations and pain quality descriptors), PROMIS Pediatric Short Forms for pain interference, anxiety, and depressive symptoms, the Adolescent Sleep Wake Scale for sleep quality, and the Pain Catastrophizing Scale. Clinical characteristics and healthcare utilization outcomes were abstracted from electronic medical records including number of inpatient admissions for pain and emergency department visits for pain in the prior 12 months.
Chronic SCD pain subgroups were based on sensory pain characteristics including pain intensity ratings, pain frequency, number of body sites affected by pain, and pain quality descriptors. Hierarchical cluster analysis informed the number of clusters at the patient level. K-means cluster analysis was used to assign patients to clusters once the number of clusters was established. Clusters were compared on sociodemographics, clinical characteristics, healthcare utilization, and child psychosocial and functional outcomes.
Results: Youth (n=62) were on average (M) 13.9 years old (SD=2.5), 56% female, 95% Black or African American, and 85% Non-Hispanic/Latinx. Most (75%) had HbSS or HbSβ 0 and 67% were prescribed hydroxyurea. Hierarchical cluster analysis and k-means clustering supported a 2-cluster solution (see Figure 1). Cluster 1 (n=35; Frequent, Moderate Pain) was distinguished by significantly lower scores on worst pain intensity (M=6.4, SD=0.4), lower number of pain days per month (M=12.1, SD=2.8), fewer number of body sites affected by pain (M=8.9, SD=0.9), and lower pain quality ratings (M=15.9, SD=1.3). Cluster 2 (n=27; Almost Daily, High Pain) represented patients who reported high ratings of worst pain intensity (M=8.2, SD=0.3), daily to almost daily pain (M=20.3, SD=1.7), higher number of body sties affected by pain (M=12.5, SD=1.5), and higher ratings of pain quality (M=40.8, SD=1.9) (all p's &lt;.05). There were no differences between chronic SCD pain subgroups by sociodemographics (e.g., age, sex, family income), clinical characteristics (e.g., genotype, history of avascular necrosis, disease-modifying treatments, prescribed long-acting opioids, neuropathic medications, or antidepressants), or healthcare utilization. Patients in the Almost Daily High Pain subgroup reported significantly higher pain interference, depressive symptoms, and pain catastrophizing compared to patients in the Frequent, Moderate Pain subgroup (see Table 1). There were no differences between subgroups on anxiety or sleep quality.
Conclusions: Two subgroups of chronic SCD pain were identified based on pain, psychosocial, and functional outcomes. Beyond sensory pain characteristics, pain interference, depressive symptoms, and pain catastrophizing were the only variables that best differentiated the chronic SCD pain subgroups. These empirically derived subgroups are comparable to other non-SCD chronic pain subgroups in pediatrics and adults. Identifying homogenous chronic SCD pain subtypes can inform tailored assessment and management of chronic pain.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.