Quantitative Measurements of Hemophilic Joint Tissues By Point-of-Care Musculoskeletal Ultrasound Are Associated with Clinical and Functional Joint Outcome Parameters
Authors: Mesleh Shayeb Akram , Barnes Richard , Hanacek Cris , Flores Andres , Kruse-Jarres Rebecca , Steiner Bruno , Quon Doris , Bailey Cindy , von Drygalski Annette 
Published: February 2020

Introduction:

Recurrent joint bleeding in patients with congenital hemophilia causes progressive arthropathy, characterized by reduced range of motion, synovial proliferation and osteochondral damage. Chronic hemophilic arthropathy remains a leading disabling complication affecting activity and quality of life. Clinical scoring systems, such as the Hemophilia Joint Health Score (HJHS), along with semi-quantitative imaging modalities (radiographs, magnetic resonance, ultrasound) can aid in the evaluation of joint health. However, scores exhibit ceiling effects and lack the opportunity to provide tissue measurements reflecting subtle dynamic changes of intra-articular structures that may be important in monitoring progression of hemophilic arthropathy. Point-of-care (POC) musculoskeletal ultrasound (MSKUS) has emerged as a rapid and sensitive imaging modality to evaluate not only acute bleeding episodes but also the extent of hemophilic arthropathy at the tissue level in the clinic setting. The Joint Tissue Activity and Damage Exam (JADE) has been developed as a concise, quantitative (not semi-quantitative) MSKUS protocol, validated per Outcomes Measures in Rheumatology guidelines for accurate tissue recognition, with high intra/inter-rater and inter-operator reliability, to quantify (1/10th of millimeter) soft tissue expansion, osteochondral alterations and cartilage thickness in hemophilic joints. We aimed to explore to what extent measurable structural intra-articular tissue changes, evaluated by JADE, correlate with clinical and functional joint assessments. If the value of JADE can be established in this context, such information would enable the use of JADE as a POC precision imaging tool to guide management of hemophilic arthropathy.

Methodology:

From May 2016 to April 2019, we assessed baseline joint characteristics in a prospective multicenter study in patients with congenital hemophilia and arthropathy (age ≥18 years; n=44 patients; n = 264 joints [bilateral elbows, ankles and knees]). HJHS (a clinical assessment tool) and total arc (a functional assessment tool measuring the sum of flexion and extension degrees of motion) were also evaluated. Each joint was examined using the MSKUS JADE protocol. We analyzed the association between joint HJHS and each JADE variable (comprising measurements of soft tissue expansion, osteochondral alterations and cartilage thickness in validated sentinel positions), and between total arc and each JADE variable, by fitting random intercept models that accounted for intra-individual correlation. The outcomes were transformed to ensure normal residuals, and when necessary polynomial terms were added to fit the curve associations between outcomes and JADE variables.

Results:

A wide range of joint HJHS values (Elbow: 0 - 13, Knee: 0 - 14; Ankle: 0 - 18 [normal=0; highest abnormal 20]) and total arc values (Elbow: 48 - 158, Knee: 22 - 160; Ankle: 5 - 76) were recorded in the cohort, enabling analyses over a broad range of arthropathic changes.

Increasing HJHS and declining total arc were associated with increasing age which is consistent with deteriorating joints. Worsening arthropathy (increasing HJHS or declining total arc) of each joint were associated with JADE measurements in the expected direction including increasing soft tissue expansion, increasing length of osteochondral alterations and decreasing cartilage thickness. This is exemplified for the elbow in Figure 1, showing the associations of worsening HJHSs and arcs with increasing osteochondral alterations and decreasing cartilage thickness.

Conclusions: This study demonstrated convincing relationships between direct ultrasonographic measurements using the JADE protocol, clinical HJHS and functional arc in a broad range of arthropathic manifestations in hemophilic patients. Interestingly, changes in arc, limiting joint flexion and extension, appeared often to be closer related to ultrasound tissue measurements than HJHS, highlighting the relevance of JADE towards joint function, a parameter of particular patient interest. These findings confirm the clinical value of POC ultrasonographic direct joint tissue measurements as a precision tool to guide timely changes in the management of hemophilic arthropathy.

Disclosures

von Drygalski: University of California San Diego: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; UniQure, Bayer, Bioverativ/Sanofi, Pfizer, Novo Nordisk, Biomarin, Shire, CSL Behring: Consultancy; Hematherix Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Founder.