Point-of-care ultrasound in haemophilic arthropathy: will the HEAD-US system supplement or replace physical examination?

Over the last decades, the advent of simple-to-use, inexpensive, portable ultrasound devices, with adequate technology to examine both superficial and deep body areas with high-resolution, has boosted the growth of ‘point-of-care’ ultrasound – ultrasound performed and interpreted by the clinician – in a variety of health care settings 1. A point-of-care ultrasound approach is usually optimized by adopting a focused, decision-making strategy to answer specific clinical questions, or identify relevant biomarkers, without the need for detailed, radiological assessment. Point-of-care ultrasound is therefore not comparable with a comprehensive ultrasound examination performed by imaging specialists, but rather supports a more time–efficient, straightforward, real-time approach to critical clinical issues that may affect patient management.

In the musculoskeletal system, the value of point-of-care ultrasound is particularly apparent in multi-joint pathologies, where disease detection may be important in otherwise asymptomatic joints, and it may be useful to evaluate or adjust the appropriate treatment strategy. A typical example is rheumatoid arthritis, in which point-of-care ultrasound is successfully used as a screening tool to detect joint effusion, synovial proliferation, bone erosions and soft-tissue injuries as an adjunct to physical examination. For this purpose, approximately a third of rheumatologists currently use ultrasound on a routine basis 2.

Haemophilia is another disease area with potential to benefit from implementation of point-of-care ultrasound for routine joint assessment. The HEAD-US (Haemophilia Early Arthropathy Detection with UltraSound) system has recently been developed for non-imaging specialists, as a fast to perform technique, capable of screening six joints (the elbows, knees and ankles) in a single examination 3. The HEAD-US system has also been designed to recognize certain biomarkers reflecting disease activity and osteochondral damage 3. It is proposed that in daily practice, the HEAD-US system would find its place as a supplement to physical examination assessment tools, such as the Haemophilia Joint Health Score (HJHS), in order to provide more objective assessment of findings and increase sensitivity in detecting joint abnormalities.

The value and performance of the HEAD-US system in clinical practice is assessed by Foppen and colleagues 4 in their article published in this issue of the journal. For this purpose, the HEAD-US protocol was utilized in a challenging group of 32 children (mean age 11.5 years) free of any history of joint damage (88% of patients with haemophilia A, 94% of which had severe phenotype). Two joints per patient were examined – the joint with the highest risk of arthropathy based on lifetime bleeding history and its contralateral – for a total of 63 joints. A portable ultrasound machine equipped with conventional small-parts probes was used for this purpose. On the same day, clinical function was determined according to the HJHS scale 5.

In this study, a strong correlation (r = 0.70, P < 0.01) was observed between HEAD-US and HJHS. Interestingly, ultrasound showed abnormalities in five joints with a history of bleeds (accounting for approximately 8% of cases), one of which was negative on HJHS assessment 6. In another three cases, ultrasound examination was normal despite a slight loss of function detected by HJHS examination. Since damaged joints in children present with focal or diffuse cartilage thinning that cannot be quantified by measurements, the arbitrary choice of the authors to scan the contralateral joint as a reference seems appropriate. Nevertheless, the high incidence of unexpected abnormalities detected by point-of-care ultrasound utilizing the HEAD-US system compared with negative or slightly abnormal HJHS (range 1–2 points) would suggest a recommendation to extend HEAD-US screening to all six joints in a single examination session (possibly during periodic reviews, so as not to miss occult pathology in joints that appear clinically normal). It is widely known that joint disease in children may be subclinical due to their intrinsic hyperlaxity, and a long learning curve is required to recognize subtle changes on physical examination in this age group 7, 8. Conversely, point-of-care ultrasound according to the HEAD-US protocol requires a relatively short period of training. Systematic examination of six joints with this technique may therefore represent a time-efficient option considering the protocol is fast to perform with a mean examination time <2 min per joint. Although this issue should be further substantiated, we believe the HEAD-US system has potential to provide significant benefits as a haemophilic joint screening tool, particularly in the paediatric age group.

In the series presented by Foppen and colleagues, a number of joints appeared slightly positive on HJHS examination, but negative according to HEAD-US 6. Although the authors did not provide MR imaging correlation of ultrasound images, this might indicate some intrinsic weakness of the HEAD-US architecture to detect initial disease. Based on the need to make the system fast enough to allow six joints to be examined during routine clinical assessment, reliable enough for non-imaging specialists, and able to minimize operator-dependency, the HEAD-US architecture offers only partial evaluation of the osteochondral surfaces for damage detection 4. In addition, centrally located and weight-bearing osteochondral areas are largely masked to ultrasound examination due to difficulties of access. Although this does not appear to represent a significant limitation to use in the context of haemophilic arthropathy, as damage establishes diffusely across the joint surfaces, validation studies comparing HEAD-US scores with MR imaging are needed to establish the threshold of HEAD-US sensitivity. Additionally, certain items of the HJHS (e.g. crepitus, pain, reduced range of motion, loss of strength) may be confounding, not straightforward to assess, or might not necessarily point at arthropathy, possibly creating false positives of intra-articular disease 8. We believe the HJHS threshold to identify subtle disease activity and early damage has yet to be defined, particularly in children, and there is a potential role for ultrasound in this regard.

Where are we going after the advent of point-of-care ultrasound in the field of haemophilic arthropathy? Will HEAD-US be best utilized as an adjunct to physical examination assessment tools, such as HJHS? Or will it compete by virtue of its shorter learning curve and more objective assessment? We can only speculate as to what the future holds, however, it seems conceivable to propose a reimagining of the role of physical examination assessment tools. Perhaps by reducing the number of items to check (the same information may be provided by ultrasound imaging in a more objective form) and creating a more simplified physical examination protocol that can be used in conjunction with the HEAD-US system (to address certain biomechanical aspects that cannot be analysed through imaging alone). This would also have the advantage of making physical examination simpler to perform, without requiring dedicated physiotherapists or experienced physicians to carry out detailed joint assessments at each visit. This will be particularly useful in small/peripheral haemophilia centres, where local expertise to perform ‘state-of-the-art’ HJHS examination may fall short, due to a lack of training and dedicated personnel. As a result, physical assessment of joint status often falls below the standards of due care. We therefore hypothesize that the short learning curve of HEAD-US combined with ‘simplified’ physical tests tailored to specific aspects that are ‘blind’ at ultrasound, would offer the best potential to identify subclinical disease and influence treatment options to limit disease progression and improve clinical outcomes for people with haemophilia.

Disclosures

Carlo Martinoli has received honoraria for speaking or participating in scientific advisory boards or symposia from Pfizer. Matteo Nicola Dario Di Minno has received consultancy and speaker's fees from Bayer, Biotest, Boehringer Ingelheim, Novo-Nordisk and Pfizer. He has also received research grant funding from Novo-Nordisk and Pfizer. Gianluigi Pasta has received honoraria for speaking from Bayer, Novo-Nordisk and Pfizer. Alberto Tagliafico has declared no conflicting interests.