Pain in hand osteoarthritis is associated with crystals in the synovial fluid: a cross-sectional study of people with hand osteoarthritis undergoing surgery

• Published in: Rheumatic & musculoskeletal diseases open Vol. 9; no. 3; p. e003319
• Main Authors: Døssing, Anna, Conaghan, Philip G, K. Stamp, Lisa, M. McCarthy, Geraldine, Henriksen, Marius, Christensen, Robin, Terslev, Lene, Ellegaard, Karen, Henrik Søe, Niels, Juul, Lars, Hansen, Philip, Radev, Dimitar Ivanov, Nybing, Janus Damm, Boesen, Mikael, Bliddal, Henning
• Format: Journal Article
• Language: English
• Published: London EULAR 01.08.2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Letter
• Subjects: Analgesics; Arthritis; crystal arthropathies; Crystals; Genotype & phenotype; Hemoglobin; Inflammation; Joint surgery; Lavage; Osteoarthritis; Pain; Pathogenesis; Quality of life; Rheumatism; synovial fluid; Ultrasonic imaging; ultrasonography
• ISSN: 2056-5933; 2056-5933
• DOI: 10.1136/rmdopen-2023-003319

Intra-articular crystal deposits have been implicated in OA pathogenesis, with their ability to activate inflammatory pathways as well as cell proliferative and apoptotic reactions.1 2 For people with knee OA, basic calcium phosphate crystals in the synovial fluid are associated with worse patient-reported pain and function.3 So far, no study has investigated the association between intra-articular crystals and symptoms in hand OA. Within 4 weeks prior to surgery, participants underwent a standardised clinical examination and completed questionnaires including a Visual Analogue Scale (VAS) of finger pain, a VAS patient global assessment, the Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and the European Quality of Life 5 Dimensions (EQ-5D). Statistically significant differences in VAS pain persisted after exclusion of participants with monosodium urate crystals identified in joint fluid.Table 1 Characteristics of the included population Characteristic Reference negative: joint-associated crystals absent, n=7* Reference positive: joint-associated crystals present, n=5* Difference between groups (95% CI) Age, years 73.3 (12.1) 74.8 (12.3) −1.4 (−17.3 to 14.4) Female sex, n (%) 7 (100.0) 4 (80.0) 0.2 (−0.2 to 0.6) Weight, kg 69.1 (14.8) 83.8 (14.7) −14.7 (−34.0 to 4.5) Height, cm, median (IQR) 166.0 (163.5–166.2) 165.0 (154.0–168.0) 1.0 (−24.5 to 15.4) Symptom duration, years 10.1 (11.5) 28.2 (10.1) −18.1 (−32.3 to −3.8) Concomitant pain medication  Non-steroidal anti-inflammatory drug users, n (%) 0 (0.0) 0 (0.0) 0.0 (0.0 to 0.0)  Paracetamol users, n (%) 2 (28.6) 2 (40.0) −0.1 (−0.7 to 0.4)  Paracetamol dose among users, mg per day 1000.0 (0.0) 3500.0 (707.1) −2500.0 (−4651.3 to −348.7) Outcome measures  VAS pain fingers (0–100), mm 37.7 (22.9) 87.2 (8.9) −49.5 (−73.7 to −25.2)  AUSCAN pain (0–500) 194.4 (117.6) 376.2 (47.8) −181.8 (−307.0 to −56.5)  AUSCAN function (0–900) 354.3 (263.0) 720.4 (114.9) −366.1 (−648.3 to −83.9)  VAS patient global assessment (0–100), mm 46.3 (29.3) 51.4 (41.5) −5.1 (−50.4 to 40.2)  EQ-5D (−0.624 to 1.000), median (IQR) 0.740 (0.625–0.807) 0.660 (0.592–0.703) 0.092 (−0.213 to 0.465)  Grip strength, Newtons, median (IQR) 100.0 (63.5–145.5) 78.5 (59.0–121.8) 11.5 (−108.0 to 143.0)  Tender joint count (0–30) 5.4 (5.0) 8.8 (6.6) −3.4 (−10.8 to 4.0)  Swollen joint count (0–30) 1.4 (1.0) 2.4 (1.5) −1.0 (−2.6 to 0.6) Laboratory measures  Plasma urate, mmol/L, median (IQR) 0.30 (0.27–0.32) 0.36 (0.29–0.37) −0.06 (−0.32 to 0.02)  Ionised calcium, mmol/L, median (IQR) 1.22 (1.19–1.25) 1.23 (1.21–1.23) 0.00 (−0.07 to 0.05)  Haemoglobin 1Ac, mmol/mol, median (IQR) 39.0 (37.5–41.0) 37.5 (29.5–39.8) 1.3 (−9.0 to 32.0)  Ferritin, µg/L, median (IQR) 123.0 (100.5–190.0) 90.0 (40.2–148.5) 51.5 (−71.0 to 178.0) Baseline imaging features  Ultrasound of the joint undergoing surgery   Synovial hypertrophy (0–3), median (IQR) 3.0 (2.5–3.0) 1.0 (0.0–2.2) 1.3 (−0.0 to 3.0)   Participants with synovial hypertrophy ≥2, n (%) 7 (100.0) 2 (50.0) 0.5 (0.0 to 0.1)   Colour Doppler (0–3), median (IQR) 0.0 (0.0–0.5) 0.0 (0.0–0.0) 0.0 (0.0 to 2.0)   Participants with colour Doppler ≥2, n (%) 2 (28.6) 0 (0.0) 0.3 (−0.0 to 0.6)   Inflammation, n (%)† 7 (100.0) 2 (50.0) 0.5 (0.0 to 1.0)   Osteophyte (0–3), median (IQR) 1.0 (1.0–1.0) 1.0 (1.0–1.2) −0.0 (−1.0 to 0.0)  Cone-beam CT of the joint undergoing surgery   Erosions, n (%) 4 (57.1) 4 (80.0) −0.2 (−0.7 to 0.3)  Radiographs of the hand with the joint undergoing surgery   Chondrocalcinosis in the triangular fibrocartilage 0 (0.0%) 1 (20.0%) −0.2 (−0.6 to 0.2)   KL sum grade DIP and PIP joints (0–32), median (IQR) 20.0 (18.5–26.0) 18.0 (16.0–19.0) 2.0 (−12.0 to 12.0)   No of DIP and PIP joints with KL ≥2 (0–8), median   (IQR) 6.0 (4.0–8.0) 5.0 (5.0–6.0) 0.0 (−3.0 to 3.0)   KL grade CMC1 joint (0–4), median (IQR) 2.5 (1.2–3.0) 1.5 (0.8–2.5) 0.4 (−2.0 to 3.0)   KL ≥2 CMC1 joint, n (%) 4 (66.7) 2 (50.0) 0.2 (−0.5 to 0.8)   OARSI JSN sum score DIP and PIP joints (0–24), median (IQR) 17.0 (15.5–20.0) 15.0 (12.0–18.0) 2.0 (−8.0 to 8.0)   OARSI JSN score CMC1 joint (0–3), median (IQR) 1.5 (0.2–2.0) 1.0 (0.0–2.2) −0.0 (−2.0 to 2.0)   OARSI joint space narrowing IP joint, n (%) 3 (42.9) 1 (20.0) 0.2 (−0.3 to 0.7) Values are mean (SD) unless otherwise indicated. AUSCAN, Australian/Canadian Hand Osteoarthritis Index; CMC1, carpometacarpal-1; DIP, distal interphalangeal; EQ-5D, European Quality of Life 5 Dimensions; IP, interphalangeal; JSN, joint space narrowing; KL, Kellgren-Lawrence; OARSI, Osteoarthritis Research Society International; PIP, proximal interphalangeal; VAS, Visual Analogue Scale.