Screening for subclinical synovial proliferation in haemophilia: A systematic review and meta‐analysis comparing physical examination and ultrasound

Abstract

Introduction:Ultrasound is increasingly used as addition to physical examination for detection of subclinical joint changes in haemophilia. However, the added value of ultrasound to physical examination for detecting synovial proliferation is not fully established. Aim:To determine the diagnostic accuracy of swelling at physical examination for ultrasound-detected synovial proliferation in haemophilia. Methods: PubMed and EMBASE were searched up to 2 August 2022. Studies reporting original data on occurrence of swelling at physical examination and synovial proliferation on ultrasound of index joints in persons with haemophilia were included. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Diagnostic accuracy parameters of swelling at physical examination for ultrasound-detected synovial proliferation were determined.Summary sensitivity and specificity were calculated using a bivariate random-effects model.Results: Fifteen studies reporting on swelling at physical examination and synovial proliferation on ultrasound in 2890 joints of 627 patients were included. Prevalence of subclinical synovial proliferation ranged between 0% and 55%. Sensitivity of swelling was low [summary estimate .34; 95% confidence interval (CI) .24-.46], while specificity was high (summary estimate .97; CI .92-.99). Predictive values varied widely due to inter-study differences in prevalence of synovial proliferation. Conclusion:Joint swelling has low sensitivity for presence of ultrasound-detected synovial proliferation in haemophilia, suggesting underestimation of synovial proliferation by physical examination alone. Consequently, ultrasound screening may generate important information on synovial changes which would otherwise remain undetected.

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations

“…Synovial changes not meeting the criteria above were classified as inactive (fibrotic) subclinical synovial proliferation. 29 The annualised joint bleeding rate over 5 years was 0.6 (0.2-1.1). Active (22%) and inactive subclinical synovial proliferation (22%) were both prevalent in this cohort.…”

“…Another recent cross-sectional study by van Bergen et al, 29 which consecutively included patients with severe haemophilia A, aged 16 years and older, born after 1969, who had access to prophylaxis and were treated at the VanCreveldkliniek (UMC Utrecht, the Netherlands), reported the prevalence of subclinical synovial proliferation on US in the studied patient cohort to be 43%. The authors also proposed two subtypes of subclinical synovial proliferation in this study:…”

“…[23][24][25][26][27] Another recent systematic review and meta-analysis included fifteen studies reporting on swelling at physical examination and synovial proliferation on US in 2890 joints of 627 patients concluded that joint swelling had low sensitivity for presence of US-detected synovial proliferation in haemophilia, suggesting underestimation of synovial proliferation by physical examination alone. 28 Prevalence of subclinical synovial proliferation in the reviewed studies ranged from 0% to 55%.…”

“…It is important to highlight that the proposed definitions are yet to be validated, but the observations are of interest especially with growing interest in detecting synovial proliferation, which is associated with increased bleeding and progression of haemophilic arthropathy, 3,4,7 at an early or subclinical phase when it is presumably reversible. 28 US does have limitations, however. US does not allow for soft tissue discrimination (which includes blood clots, synovium, and fat pads) 21 or detailed and accurate assessment of the central aspect of the cartilage and subchondral bone.…”

Challenges in ageing persons with haemophilia

“…Globally, 17%-84% of PwH have reported chronic pain, although definitions of chronic pain vary amongst studies. 25 Subclinical joint bleeding has also been detected in younger and older PwH on prophylaxis, 26 and a recent study amongst PwH who were highly adherent to prophylaxis identified that only two-thirds of 97 children and one-third of 176 adults were bleed-free. 27 The influence of age on the clinical profile of pain also warrants consideration, as adults who commenced secondary or tertiary prophylaxis may live with more severe arthropathy, longstanding chronic pain and physical dysfunction compared to younger PwH on primary prophylaxis.…”