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.