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A new wave in the evaluation of haemophilic arthropathy

Haemophilic arthropathy (HA), characterized by synovial hypertrophy, cartilage and bony destruction, results from repeated bleeding episodes in the joint and constitutes the single largest cause of morbidity in persons with haemophilia (PwH) [1]. HA is complex and multifactorial, and its pathophysiology remains incompletely understood. Despite advances in coagulation factor replacement therapy and the early institution of prophylactic infusion regimens, debilitating joint disease continues to occur [2,3]. This issue was recently highlighted in a birth cohort analysis of men with haemophilia born over five decades in the United States which revealed that despite improved access to comprehensive care and pathogen-free clotting factor, one-third to one-half of men born in more recent decades across all ages experienced frequent bleeding, and the disability gap between severe and mild haemophilia had not narrowed either for target joints or for use of assistive devices for mobility [4]. Albeit disappointing, these findings underscore the fact that despite advancements in the prevention, detection and management of HA, a gap continues to exist in our ability to detect and impact this sequela at the preclinical or asymptomatic phase when the disease process is early and potentially reversible. Joint assessment in haemophilia is a continuously evolving process. Currently, in addition to clinical assessment tools [World Federation of Haemophilia Physical Examination Score (Gilbert score) and the haemophilia joint health score (HJHS) [5,6]], several imaging modalities have been employed for joint status evaluation and monitoring disease progression over time. The quest for the ‘best’ imaging modality is at least a century old and is driven by two key factors: dependence on patient-related symptoms and physician-observed signs are unreliable [7] and clinical joint assessment tools are relatively insensitive to changes in the very early and very late stages of joint disease. While X-rays are widely available and may capture advanced joint changes, they are insensitive to early change and unreliable for cartilage and soft tissue evaluation [8]. Joint MRI is considered the gold standard for evaluation of HA [9,10], providing detailed multi-tissue evaluation and increased sensitivity to early pathology and changes over time. MRI is time consuming, costly, not readily accessible for all and may require sedation in young children. Therefore, early arthropathic changes are often not detected in children or adults in whom obtaining ‘baseline’ MRI scans of multiple clinically asymptomatic or nearly asymptomatic joints may be unjustifiable and cost ineffective. In addition, MRI may detect a large number of minor changes over time which may not all be necessarily clinically meaningful and their impact on joint outcomes is yet to be determined [11,12]. For these reasons, joint ultrasound (US) has emerged as a readily accessible, fast, dynamic, less expensive and safe imaging modality for early detection and management of HA in ‘real time’ [6,12,13]. Compared to MRI, US does not require sedation in children and does not have the interference of susceptibility artefacts commonly seen on gradient-echo MRI sequences including the ‘blooming’ effect with haemosiderin deposition [14]. While the interest in this imaging modality has grown, US’s reliability, diagnostic accuracy and impact on joint outcomes in haemophilia have been the subject of debate and controversy [8,13,15,16]. To critically review its role, one must have a clear understanding of different US techniques and the variety of applications in evaluation and management of HA. From an US technique standpoint, both full joint and point-of-care highresolution musculoskeletal US (POC-MSKUS) are currently used for this purpose. Full joint US is performed by trained radiologists and ultrasonographers for a 360° joint assessment using all standard scanning planes. In contrast, POC-MSKUS may be performed by trained clinicians in an outpatient setting using fewer scanning planes per joint to address specific yes-no questions regarding haemarthrosis, synovial hypertrophy, osteochondral abnormalities etc. In both techniques, the operator uses high-resolution probes, which allow for visualization of Correspondence: Nihal Bakeer, MD, Indiana Hemophilia and Thrombosis Center, 8326 Naab Road, Indianapolis, Indiana, 46260, USA. Tel.: +1 317-871-0000; fax: 317-871-0010; e-mail: nbakeer@ ihtc.org