Imaging of Haemophilic Arthropathy

Abstract

Haemophilia is an X-linked recessive genetic disorder characterized by spontaneous or trauma-related bleeds, especially in large joints. Repeated provoked or spontaneous joint bleeds are the hallmark of severe haemophilia. Recurrent or prolonged joint bleeds eventually lead to synovial hypertrophy, progressive cartilage degradation and bone damage through mechanical and metabolic joint destruction. Imaging of joints has always played an important role to assess outcome in haemophilia. Haemophilic arthropathy can be assessed using imaging techniques such as X-rays, Magnetic Resonance Imaging (MRI), and ultrasound. These techniques were evaluated in this thesis.

Key findings The radiological Pettersson score is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. The reliability and agreement (reproducibility) of the Pettersson score was studied in this thesis to evaluate to what extent differences in scores are attributable to observer-variation. A consensus atlas with reference images for scoring was developed which resulted in an improved reproducibility among observers.

With the increasing interest in MRI assessment of joints in haemophilia, the questions arise regarding the clinical meaning of MRI findings. In order to provide context for joint evaluation with MRI in young haemophilia patients, a cohort of young active healthy men was evaluated by MRI. Results suggested that sports participation is not associated with haemophilia specific MRI changes. A comparison of joint effusion between haemophilia patients and young active healthy controls showed that joint effusion on MRI is unlikely to be haemophilia specific.

So far, the prognostic value of MRI findings was based on assumptions only. This thesis shows that the bleeding risk is significantly increased in joints with synovial hypertrophy. In addition, haemophilia specific MRI findings in joints without changes on X-rays are associated with progression of arthropathy five years later. Therefore, it may be beneficial to guide treatment based on MRI findings.

As an alternative for joint evaluation with MRI, ultrasound might be more practicable in daily practice. Across different medical specialties, non-radiologists increasingly use point-of-care ultrasound (POC-US) for procedural, diagnostic, and screening purposes. In this thesis it was established that POC-US provides an accurate alternative for MRI for the assessment of synovial hypertrophy in young adults with limited arthropathy.

Clinical applications For both clinical care and research, the optimal imaging modality depends on the clinical joint status. X-rays are mostly indicated for moderate-severe arthropathy as they are insensitive to early joint changes. MRI is the most sensitive imaging modality for the assessment of initial joint changes such as synovial hypertrophy, haemosiderin deposits, and cartilage defects. Its use is therefore recommended for assessment of the progression of arthropathy, or to evaluate the origin of clinical complaints. As synovial hypertrophy on MRI showed to be associated with an increased joint bleeding risk, treatment may be monitored or tailored based on the presence/absence of synovial hypertrophy on imaging. As the availability of MRI is limited, POC-US provides an accurate alternative for routine assessment of synovial hypertrophy.