Acute pain in sickle cell disease (SCD) involves multiple, complex downstream effects of vaso-occlusion, ischemia, and inflammation, ultimately resulting in severe and sudden pain. Historically, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) have been the cornerstone of treatment for acute SCD pain. However, given the evolving understanding of the complexity of pain pathways in SCD and the desire to avoid NSAID and opioid-induced side effects, a multimodal approach is needed to effectively treat acute SCD pain. In this article we review recent research supporting the utilization of nonopioid pharmacologic interventions and nonpharmacologic interventions while also describing the research questions that remain surrounding their use and efficacy and effectiveness in the management of acute SCD pain. Furthermore, we review care delivery processes shown to improve acute SCD pain outcomes and highlight areas where more work is needed. Through this comprehensive approach, alternative mechanistic pathways may be addressed, leading to improved SCD pain outcomes.

Human parvovirus B19 causes life-threatening anemia due to transient red cell aplasia (TRCA) in individuals with sickle cell disease (SCD). Children with SCD experiencing profound anemia during TRCA often require red blood cell transfusions and hospitalization. The prevalence of vitamin deficiencies in SCD is high and deficiencies are associated with respiratory and pain symptoms, but the effects of vitamins on acute infection with parvovirus B19 remain unclear. We performed a clinical study in which 20 SCD patients hospitalized with parvovirus B19 infections (Day 0) were monitored over a 120-day time course to query relationships between vitamins A and D and clinical outcomes. There were significant negative correlations between Day 0 vitamin levels and disease consequences (e.g., red blood cell transfusion requirements, inflammatory cytokines). There were significant positive correlations (i) between Day 0 vitamins and peak virus-specific antibodies in nasal wash, and (ii) between Day 0 virus-specific serum plus nasal wash antibodies and absolute reticulocyte counts. There was a significant negative correlation between Day 0 virus-specific serum antibodies and virus loads. To explain the results, we propose circular and complex mechanisms. Low baseline vitamin levels may weaken virus-specific immune responses to permit virus amplification and reticulocyte loss; consequent damage may further reduce vitamin levels and virus-specific immunity. While the complex benefits of vitamins are not fully understood, we propose that maintenance of replete vitamin A and D levels in children with SCD will serve as prophylaxis against parvovirus B19-induced TRCA complications.

Effective transition programs are essential for adolescents and young adults with sickle cell disease (SCD), yet their long-term impact remains unexplored. The St. Jude SCD Transition Program provides structured transition interventions, such as disease education, personal health record (PHR) communication training, transition skills-building, academic guidance, and early adult care introduction for patients aged 12 to 25 years. This 13-year retrospective cohort study evaluated program effectiveness on first adult visit attendance, successful transfer to adult care, adult ambulatory and acute care use, and health-related quality of life (HRQOL). Among 638 patients, 74.5% attended their first adult visit and 40.0% successfully transferred to adult care (2 visits within the first year after transfer). Increased participation in nearly all transition interventions was associated with first adult visit attendance, and all interventions were associated with successful transfer. In-person SCD education and early introduction to adult care were independently associated with first adult visit attendance, whereas in-person SCD education and PHR training were independently associated with successful transfer. A predictive model incorporating intervention exposure and demographics yielded an area under the curve of 0.81 for attendance at the first adult visit (95% confidence interval, 0.75-0.88; sensitivity 0.76, specificity 0.70). PHR training was associated with adult ambulatory use up to 3 years after transfer and improved early adulthood HRQOL. No interventions were associated with acute care use. Transition interventions that improve disease literacy, communication, and care transfer processes are linked to better transition outcomes and HRQOL, though sustained adult care engagement remains low. Future research is needed to promote adult care engagement.