LAUSR

In this issue of the British Journal of Haematology, Grace et al. describe longitudinal reports of fatigue in 120 paediatric patients with immune thrombocytopenia (ITP) being treated with second-line therapies in the largest reported observational study in paediatrics. While bleeding is the most obvious and potentially life-threatening complaint in ITP, fatigue is a common yet underreported and underrecognized symptom. The prevalence, natural history and pathophysiology of fatigue in ITP are not known, and it is unclear whether treatment may improve fatigue. The authors of this study quantitatively assess fatigue in this paediatric population and describe the relationship between fatigue and clinical variables like treatment therapy, age, bleeding symptoms, and treatment response. Immune thrombocytopenia is an autoimmune disorder that results in antibody-mediated destruction of platelets and decreased platelet production, leading to thrombocytopenia and bleeding. In addition to bleeding, fatigue is now recognized as a common and debilitating symptom that negatively impacts quality of life (QoL). The causes of ITP-related fatigue are not clearly understood, but treatment side effects, anxiety and depression may be contributing factors. In fact, adults with ITP report decreased QoL compared to controls, similar to other chronic conditions like cancer, arthritis and hypertension. Fatigue is often thought of as subjective and difficult to quantify, in contrast to objective findings like blood counts or other laboratory values or vital signs, and thus is underreported, undertreated and understudied. Due to this subjectivity, most providers do not objectively assess fatigue using a validated method and it remains unclear what effect ITP treatments have on fatigue. The patient cohort in this study is comprised of 120 children and adolescents age 1–17 years diagnosed with ITP who are starting monotherapy with second-line treatments. Patients were not included if they had current or prior autoimmune haemolytic anaemia or were receiving standard therapies including observation alone, corticosteroids, anti-D immunoglobulin, intravenous immunoglobulin or combinations of these treatments. The patients included in this report were part of the ICON1 longitudinal observational cohort, in which 120 paediatric patients were enrolled from 21 institutions in North America from 2013 to 2015 in order to examine physician decision-making. At study enrollment, 53% of patients had chronic ITP, with the remainder in the acute (16%) or persistent phases (31%). The second-line treatments included rituximab (36%), romiplostim (26%), eltrombopag (17%), oral immunosuppressant (16%), splenectomy (3%) or dapsone (3%). The authors measure fatigue using the Hockenberry Fatigue Scale (FS), which is a validated tool used to assess fatigue as an independent outcome, making this the first study to directly report fatigue as an independent outcome instead of indirectly by use of a QoL form. This is important because prior paediatric studies report fatigue within the context of health-related QoL assessments. A high prevalence of fatigue was reported at study entry, with 54% of children and 62% of adolescents reporting moderate to severe fatigue. Additionally, the parent-proxy reports of fatigue correlated with the patient self-reports. The high prevalence of fatigue may be influenced by the relatively high number of patients starting second-line treatments in the acute and persistent phases of ITP, possibly representing a population with severe symptoms or refractory disease. Overall health-related QoL was also measured using the Kids ITP Tool (KIT) at baseline, 1 and 12 months after initiating second-line therapy. The fatigue scores negatively correlated with KIT scores, highlighting the poor QoL in those with high levels of fatigue. These data confirm the validity and reliability of the Hockenberry FS in children, adolescents and parents. Correspondence: Michael H. White, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia 30322, USA. E-mail: [email protected] commentary