Spinal Pain in Sickle Cell Disease: A Scoping Review
Fabrizio Darby, Rahul H Jayaram, George Sun, Kashif Qureshi, Sujai Arakali, Viveka Chinnasamy, Anudeep Yekula, Carlos Goulart, Mihir GuptaAbstract
Background
The spine is one of the most common sites of pain among individuals with sickle cell disease (SCD), and vertebral fractures affect a high proportion of adults. However, there is limited understanding of the pathophysiology, risk factors, prevention strategies, and treatment guidelines for spinal pathologies in SCD. In this study, we performed a scoping review to describe SCD-related spinal conditions, focusing on the pathophysiology underlying these changes and associated symptoms.
Methods
A systematic search was conducted using keywords (Table 1) to identify abstracts from the PubMed, Embase, Scopus, Web of Science, and Global Index Medicus databases. Screening for titles and abstracts, as well as full texts, was conducted by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Figure 1). A third reviewer resolved all conflicts. Five independent investigators manually extracted data from relevant articles. Due to the heterogeneity of the data collected, a narrative synthesis of the extracted articles was conducted by five investigators with medical expertise, under the guidance of two neurosurgeons with fellowship training in spinal surgery.
Results
A total of 86 studies were extracted, from 1538 studies screened (Figure 1). Spinal pathologies associated with SCD included vertebral fractures (‘H-shaped’ vertebrae); increased propensity to spinal column infection; and an increased risk of spinal cord infarction. Treatment strategies for these conditions were also highlighted. There were no major associations noted in the study populations based on gender. Representative studies examined how vertebral involvement in SCD evolves on cross-sectional neuroimaging including MRI and CT scans. In the acute phase, MRI detected marrow edema with low T1 and high T2 signal, mild vertebral expansion, and rim or heterogeneous enhancement. In the late subacute and chronic phases, CT and radiographs performed similarly to MRI to detect vertebral height loss, sclerosis, fibrosis, and fat degeneration. Further study is needed to distinguish acute bone ischemia from osteomyelitis, which can appear similar on conventional MRI with bone expansion and high T2 signal from marrow edema. High clinical suspicion is required for infectious complications such as vertebral osteomyelitis, discitis and epidural abscess, with a different spectrum of causative organisms from the general population with SCD. Multiple studies documented series of children with SCD found to have Salmonella osteomyelitis, highlighting the role of functional asplenia in the pathogenesis of this infection. There remains a paucity of treatments specifically targeting musculoskeletal mechanisms responsible for spinal pathologies in SCD. Opioid analgesics continue to be mainstays of pain management and have been used in conjunction with non-opioid analgesics. A variety of nonpharmacologic pain management modalities were also described, including relaxation techniques, hypnosis, heat, ice, and acupuncture. In addition to treatment, some studies also employed prevention strategies, with an emphasis on bone health. Emerging evidence suggests that at least five years of alendronate administration can increase lumbar bone mineral density among adults with SCD, in conjunction with other agents such as hydroxyurea, vitamin D, and calcium supplementation. The disease-modifying effects of hydroxyurea have been proposed to prevent various comorbidities related to SCD. However, our results suggest that evidence for both lumbar bone density improvement and hydroxyurea treatment specifically with regards to preventing spinal pathologies remains limited.
Conclusions
This study synthesizes the numerous articles exploring spinal pathologies associated with SCD. Drawing upon unique historical and global investigations, we identify several areas in which pathophysiologic understanding and management strategies have not kept pace with the advancements in other areas of SCD research and clinical practice. This study serves as a framework for understanding a highly prevalent aspect of musculoskeletal health contributing to chronic pain in SCD, for which therapeutic advances are urgently needed.