Introduction

Sickle cell disease (SCD) is the most common monogenetic hemoglobinopathy in the world with approximately 300,000 newborns per year.1,2 SCD is caused by a gene mutation in the beta-globin chain, resulting in the formation of sickle-shaped red blood cells.3,4 These sickled red blood cells cause obstruction within small vessels, leading to chronic hemolytic anemia, acute and chronic pain and irreversible organ damage.5
Pain is the clinical hallmark of SCD and has a huge impact on patients’ daily life leading to a decreased health-related quality of life.6-10 Because of the complexity of pain in SCD patients and the scarce knowledge of its pathophysiology, the management of SCD-related pain is extremely difficult.11,12 Acute pain from vaso-occlusive crises (VOCs) can be managed at home using oral or suppository analgesic agents.13,14 In case home management fails, hospital admission is required for treatment with intravenous analgesics, anxiolytics and/or sedatives.15,16 Pharmacological interventions such as opioid analgesics have been the primary therapy to treat SCD-related pain. However, they can have serious side effects including respiratory depression and constipation on the short term and physical dependence on the long term. Although pharmacological treatment is the backbone of SCD-related pain, non-pharmacological management has proven to be effective in reducing pain in several diseases, including SCD.17-23 Both the National Heart, Lung and Blood Institute (NHLB) and the American Society of Hematology (ASH) guidelines (2020) indicated non-pharmacological interventions as a valuable addition in the management of SCD-related pain.14According to the ASH guidelines non-pharmacological interventions can be classified into: the psychological interventions, physical interventions, and integrative medicine.14,17
Previous reviews have investigated the efficacy of complementary non-pharmacological interventions in reducing pain in patients of all ages seven years ago.21,22 In this review we specifically focus on the effect of these interventions on SCD-related pain in children. Children experience pain differently compared to adults, as children have a developing and more adaptable nervous system, a greater developmental potential, and more cognitive and emotional flexibility.24-30 This allows greater potential change, behavioral improvement and effectiveness of non-pharmacological interventions.31 In addition, frequent pain experiences during childhood can cause negative long-term effects that may last into adulthood including a higher sensitivity to pain and anxiety and depression.32-38 Therefore, the aim of this systematic review is to investigate the effect of non-pharmacological interventions on (1) the frequency and/or intensity of SCD-related pain, and (2) analgesic and health service use in children with SCD.