Inflammation, angiogenesis and sensory nerve sprouting in the synovium of bony ankylosed and not bony ankylosed knees with end-stage haemophilic arthropathy

Introduction: Clinical practice showed that patients with haemophilia (PwH) with bony ankylosed end-stage haemophilic arthropathy knees reported milder pain than those with not bony ankylosed knees.

Aim: To compare the differences in pain sensation and the histopathological differences in synovial samples of affected knee joints between PwH with bony ankylosed end-stage haemophilic arthropathy knees and those with not bony ankylosed knees.

Methods: From January 2011 to December 2019, the synovial samples of knee joints were collected during total knee arthroplasty (TKA) surgery for end-stage haemophilic arthropathy. The visual analogue scale (VAS, 0-10) pain score was reviewed from the chart data of the patients. The thickness of the inner layer of the synovium in haematoxylin and eosin (H&E) staining sections was measured. The expression levels of Ki67, IL-1β, TNF-α, CD31, VEGF, NGF and PGP9.5 in the synovium were detected by immunohistochemistry (IHC) method.

Results: Fifty-two end-stage haemophilic arthropathy knee synovial samples from 36 male PwH (34 type A and 2 type B) were collected. Fifteen knees had bony ankylosed (BA-group), and 37 were not bony ankylosed (Not-BA-group). The mean age of patients at TKA surgery of BA-group and Not-BA-group was 32 years (15) and 32 years (10), respectively (p = 0.824). Before TKA surgery, the mean VAS pain scores of patients in the Not-BA-group were significantly higher than those in the BA-group (p < 0.001). The mean thickness of the inner layer of the synovium, the mean rate of Ki67+ cells, the mean density of CD31+ vascular endothelial cells and the expression levels of IL-1β, TNF-α, VEGF and NGF in samples in the Not-BA-group was significantly higher than those in samples in the BA-group (p < 0.001, p = 0.02, p = 0.001, p = 0.117, p < 0.001, p = 0.003 and p = 0.008), respectively. The mean density of PGP9.5+ sensory neural fibres in the Not-BA-group was slightly higher than in the BA-group (p = 0.131). Linear regression analysis showed a significant positive correlation between the VAS pain score and indicators including the synovial thickness, the rate of Ki67+ cells, the expression level of IL-1β, TNF-α, VEGF, NGF and the densities of CD31+ vascular endothelial cells and PGP9.5+ nerve fibres (p < 0.05).

Conclusions: Worsened hypertrophic synovitis, angiogenesis and sensory nerve sprouting in the synovium may play a critical role in causing worse pain sensation in PwH with not bony ankylosed haemophilic arthropathy knees than in those with bony ankylosed knees.