Subclinical synovial proliferation in patients with severe haemophilia A: The value of ultrasound screening and biochemical markers

Aim

Subclinical bleeding and inflammation play a role in progression of haemophilic arthropathy. Synovial proliferation is predictive of joint bleeding and its early detection may guide treatment changes and prevent arthropathy progression. This study evaluated the prevalence of active and inactive subclinical synovial proliferation and investigated potential biochemical blood/urine markers to identify patients with active subclinical synovial proliferation.

Methods

This cross-sectional study included patients with severe haemophilia A born 1970–2006 who were evaluated during routine clinic visits. Patients with (a history of) inhibitors or recent joint bleeding were excluded. Elbows, knees and ankles were examined for subclinical synovial proliferation by ultrasound and physical examination. Active synovial proliferation was distinguished from inactive synovial proliferation using predefined criteria. Blood/urine biochemical markers (serum osteopontin, sVCAM-1, Coll2-1, COMP, CS846, TIMP, and urinary CTX-II) were compared individually and as combined indexes between patients with and without active synovial proliferation.

Results

This cohort consisted of 79 patients with a median age of 31 years (range 16.5–50.8 years) with 62/79 (78%) of the patients using continuous prophylaxis. The annualized joint bleeding rate over the last 5 years was .6 (.2–1.1). Active (17/79, 22%) and inactive subclinical synovial proliferation (17/79, 22%) were both prevalent in this cohort. Biochemical markers were not correlated with active subclinical synovial proliferation.

Conclusion

Subclinical synovial proliferation, both active and inactive, was prevalent in patients with severe haemophilia A with access to prophylaxis and would be overlooked without routinely performed ultrasounds. Biochemical markers were unable to identify patients with active subclinical synovial proliferation.     

Clotting factor activity levels and bleeding risk in people with haemophilia playing sports

Background

Improved treatment options for people with haemophilia (PWH) have increased the possibilities for sports participation, but the risk of sports-induced bleeding (SIB) is still considered considerable by many.

Aim

To assess sports associated injury- and bleeding risk in PWH and to assess clotting levels associated with safe sports participation.

Methods

Sports injuries and SIBs were prospectively collected for 12 months in PWH aged 6–49 without inhibitors playing sports at least once weekly. Injuries were compared according to factor levels, severity, joint health, sports risk category and sports intensity. Factor activity at the time of injury was estimated using a pharmacokinetic model.

Results

125 participants aged 6–49 (41 children, 90% haemophilia A; 48% severe, 95% severe on prophylaxis) were included. Sports injuries were reported by 51 participants (41%). Most participants (62%) reported no bleeds at all and only 16% reported SIBs. SIBs were associated with factor levels at time of injury (OR: 0.93/%factor level (CI 0.88–0.99); p = .02), but not with haemophilia severity (OR: 0.62 (CI 0.20–1.89); p = .40), joint health, sports risk category or sports intensity. PWH with factor levels <10% during sports injury had a bleeding risk of 41% versus 20% in those with higher (>10%) factor levels.

Conclusion

The results of this study emphasize the importance of clotting factor levels in prevention of bleeds. This information is vital for patient counselling and tailoring prophylactic treatment with clotting factors and non-replacement therapy.     

Monitoring recovery of joints after bleeding: Physical examination and ultrasound are complementary

Aim

Traditionally, recovery after a joint bleed in people with bleeding disorders is evaluated by clinical symptoms. Following a bleed, however, asymptomatic joints may still show synovial hypertrophy and effusion on ultrasound. We evaluated the duration of full recovery from a joint bleed. Additionally, we determined how recovery differed when assessed by physical examination and ultrasound.

Methods

In this retrospective cohort study, we investigated joint bleeds in elbows, knees and ankles of people with haemophilia or Von Willebrand disease who attended the Van Creveldkliniek between 2016 and 2021. Physical examination (warmth, swelling, range of motion and gait) and ultrasound (effusion and synovial hypertrophy) were performed within 7 days after the onset of the bleed, 1 week after the first examination and monthly thereafter until patients had recovered fully. Joint bleeds were treated in line with the current international treatment guidelines.

Results

We evaluated 30 joint bleeds in 26 patients. The median recovery time was 1 month (range 0.3-5 months). In 47% of the joint bleeds, the recovery took longer than 1 month. The moment of recovery based on physical examination and ultrasound differed in 27% of bleeds. Both persistent abnormalities at physical examination in joints with normalized ultrasounds and persistent ultrasound findings in clinically recovered joints occurred.

Conclusion

Joint bleed recovery can take long and recovery times differed per bleed. Recovery differed when assessed by physical examination or ultrasound. Therefore, both should be used to closely monitor recovery of joint bleeds and offer personalized care.     

The role of selective angiographic embolization of the musculo-skeletal system in haemophilia

Summary.  The incidence of haemarthrosis as a result of a spontaneous periarticular aneurysm in haemophilia is very low. In these circumstances, angiographic embolization might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels. Moreover, embolization should be considered as a possible treatment for postoperative pseudoaneurysms complicating total knee arthroplasty in haemophilia. However, the pathological process of aneurysmal bleeding and clotting factor replacement is entirely different. While embolization is the treatment of choice for some periarticular complications that may occur, it is by no means a panacea for all resistant periarticular bleeds in haemophilia or for postoperative bleeding which usually settles with clotting factor replacement. Another use of arterial embolization is for the treatment of haemophilic tumours of the pelvis, because they can act as a focus for infection and cause cutaneous fistulas. When they present perforations and infections of endogenous origin, their course is usually fatal. Suitable treatment has been investigated on numerous occasions, most of the literature agreeing that the only curative treatment is surgical resection. However, surgical resection after performing arterial embolization to reduce the vascularization of the pseudotumour is a good alternative, thereby reducing the size of the pseudotumour and the risk of bleeding complications during surgery. It is important to bear in mind that despite its efficacy, arterial embolization is an invasive procedure with a reported rate of complications up to 25% (16% minor, 7% serious, 2% death).     

Radiographic prognosis of finger joint damage predicted by early alteration in synovial vascularity in patients with rheumatoid arthritis: Potential utility of power doppler sonography in clinical practice

Objective

To investigate the relationship between synovial vascularity and progression of structural bone damage in each finger joint in patients with rheumatoid arthritis (RA) and to demonstrate synovial vascularity as a potential therapeutic marker.

Methods

We studied 250 metacarpophalangeal (MCP) and 250 proximal interphalangeal (PIP) joints of 25 patients with active RA who were administered adalimumab or tocilizumab. Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at the fourth and eighth weeks. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and the twentieth week.

Results

Clinical indices such as the 28‐joint Disease Activity Score, the Clinical Disease Activity Index, and the Simplified Disease Activity Index were significantly decreased by biologic agents. The MCP and PIP joints with no response in synovial vascularity between baseline and the eighth week (vascularity improvement of ≤70% at the eighth week) showed a higher risk of radiographic progression compared with responsive joints (vascularity improvement of >70% at the eighth week; relative risk 2.33–9). Radiographic progression at the twentieth week was significantly lower in responsive joints than in nonresponsive joints.

Conclusion

The improvement of synovial vascularity following treatment with biologic agents led to suppression of radiographic progression of RA in each finger joint. The alteration in synovial vascularity numerically reflected therapeutic efficacy. Using vascularity as a marker to determine the most suitable therapeutic approach would be beneficial for patients with active RA.     

Change of synovial vascularity in a single finger joint assessed by power doppler sonography correlated with radiographic change in rheumatoid arthritis: Comparative study of a novel quantitative score with a semiquantitative score

Objective

To investigate the relationship between synovial vascularity assessed by quantitative power Doppler sonography (PDS) and progression of structural bone damage in a single finger joint in patients with rheumatoid arthritis (RA).

Methods

We studied 190 metacarpophalangeal (MCP) joints and 190 proximal interphalangeal (PIP) joints of 19 patients with active RA who had initial treatment with disease‐modifying antirheumatic drugs (DMARDs). Patients were examined by clinical and laboratory assessments throughout the study. Hand and foot radiography was performed at baseline and the twentieth week. Magnetic resonance imaging (MRI) was performed at baseline. PDS was performed at baseline and the eighth week. Synovial vascularity was evaluated according to both quantitative and semiquantitative methods.

Results

Quantitative PDS was significantly correlated with the enhancement rate of MRI in each single finger joint. Comparing quantitative synovial vascularity and radiographic change in single MCP or PIP joints, the level of vascularity at baseline showed a significant positive correlation with radiographic progression at the twentieth week. The change of vascularity in response to DMARDs, defined as the percentage change in vascularity by the eighth week from baseline, was inversely correlated with radiographic progression in each MCP joint. The quantitative PDS method was more useful than the semiquantitative method for the evaluation of synovial vascularity in a single finger joint.

Conclusion

The change of synovial vascularity in a single finger joint determined by quantitative PDS could numerically predict its radiographic progression. Using vascularity as a guide to consider a therapeutic approach would have benefits for patients with active RA.     

Successful treatment of severe bleeding in hemophilic target joints by selective angiographic embolization

Bleeding into the joints is common in patients with hemophilia. After total knee or elbow replacement, profuse intraarticular bleeding unresponsive to high-dose clotting factor replacement sometimes occurs. In some patients who have severely damaged elbow or knee joints the same profuse bleeding pattern can be seen. To control bleeding in these patients, selective catheterization with a microcatheter and therapeutic embolization with microcoils was performed whenever a severe blush or microaneurysm was observed on angiography. Over 12 years, in 23 cases of massive joint bleeding in 18 patients with hemophilia selective catheterization was performed. In 15 cases the bleeding was postoperative and in 8 spontaneous. Results of angiographic imaging revealed vascular blush, false aneurysm, true aneurysm, and arteriovenous shunt in combination with an aneurysm as cause of bleeding. In 2 patients, the cause of bleeding was not found. In 21 cases an embolization procedure was performed, in which the bleeding was completely controlled by a single procedure in 14 cases. Recurrence of the bleeding occurred in 7 cases and required a second embolization procedure; in one patient even a third embolization was required to stop the bleeding completely. No difference in the outcome, that is, clinical end of bleeding and joint range of motion, was observed, when comparing postoperative and spontaneous bleeding.     

Ultrasound Joint Inflammation in Rheumatoid Arthritis in Clinical Remission: How Many and Which Joints Should Be Assessed?

Objective

To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission.

Methods

Sixty‐seven RA patients (50 women, 17 men) in clinical remission as judged by their consultant rheumatologist and treated with methotrexate were prospectively recruited. Patients were evaluated for disease activity according to the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI) by the same investigator. Each patient underwent a 44‐joint B‐mode and power Doppler (PD) assessment by a rheumatologist blinded to the clinical and laboratory data. B‐mode synovial hypertrophy (SH) and synovial PD signal were scored from 0–3 at each joint. Global indices for SH and PD signal were calculated for the 44‐joint and different joint combination models for each patient.

Results

SH was detected in 87.8% of patients with a DAS28 <2.6 and in 81.8% of patients with an SDAI <3.3. Synovial PD signal was detected in 46.3% of patients with a DAS28 <2.6 and in 36.4% of patients with an SDAI <3.3. Wrist, second through fifth metacarpophalangeal (MCP), ankle, and second through fifth metatarsophalangeal (MTP) joint and 12‐joint US assessments showed the highest correlations with the comprehensive US assessment. The wrist, MCP, ankle, and MTP joint US assessment showed the highest sensitivity for detecting SH and synovial PD signal in patients in remission according to the DAS28 and SDAI as compared to the comprehensive US assessment.

Conclusion

US assessment of the wrist, MCP, ankle, and MTP joints can be highly sensitive for detecting residual B‐mode and Doppler joint inflammation in RA patients.     

New images in haemophilia

Summary.  New imaging techniques are valuable for the care of patients with haemophilia. On angiography it is shown that some bleedings in severely damaged joints or after implantation of prostheses are arterial. Effect of clotting factor is often poor. Selective catherization with embolization of the bleeding artery stops the bleed and is clinically effective. From 31 patients with severe haemophilia A or B, 62 knee radiographs were scored according to the Pettersson-scoring system as well as with Knee Digital Image Analysis (KIDA). Using KIDA, good correlation was found for osteoporosis, irregular subchondral surface, narrowing of the joint space, deformity and incongruence. For each of the parameters within one point in the Pettersson score a large variation existed in KIDA grading. MRI is accurate for diagnosis of soft and osteochondral tissue. Nevertheless, it is costly and not very accessible. The use of parallel imaging is more feasible for assessment of multiple joints within a relatively short period of time. Although ultrasonography also holds the potential for being an adjunct to MRI it has the disadvantage that it is operator-dependent. In a cohort of 124 chronically HCV infected haemophilia patients transient elastography was performed to measure liver stiffness. 57 (46%) had no or mild fibrosis, 18 (14.5%) moderate fibrosis and 49 severe or cirrhotic fibrosis. Transient elastography is safe and helpful to refer patients to antiviral therapy.     

Real‐world comparative analysis of bleeding complications and health‐related quality of life in patients with haemophilia A and haemophilia B

Introduction

Clinical severity and impact of haemophilia on quality of life have been generally considered to be lower for haemophilia B (HB) compared with haemophilia A (HA) patients.

Aims

To compare annual bleeding rate (ABR), target joint development and health‐related quality of life (HRQoL) between adult (≥18 years) severe HA and HB patients using recent data from the Cost of Haemophilia in Europe: a Socioeconomic Survey (CHESS) study.

Methods

Multivariate generalized linear models (GLM) were constructed to assess the relationship between haemophilia type, ABR, HRQoL (derived from EQ‐5D index scores) and the presence of target joints while controlling for covariates.

Results

Of the 1225 patients included, 77% (n = 949) had HA and 23% (n = 278) had HB. Of the 514 patients who completed the EQ‐5D, 78% (n = 405) had HA, and 22% (n = 110) had HB. Unadjusted mean ABR was 3.79 in HA and 4.60 in HB. The presence of ≥1 target joint was reported in 59% and 54% of patients with HA and HB, respectively. Unadjusted mean EQ‐5D index score was 0.78 in HA and 0.76 in HB. Haemophilia type was not a significant predictor of ABR, target joints or HRQoL when adjusted for confounding factors such as BMI, age and replacement therapy regimen.

Conclusion

Data suggest comparable ABR, incidence of target joints and HRQoL between patients with HB and HA indicating comparable clinical severity and disease impact on patient quality of life.     

Comparison of clinical versus ultrasound‐determined synovitis in juvenile idiopathic arthritis

Objective

To compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with juvenile idiopathic arthritis (JIA).

Methods

Thirty‐two patients underwent clinical evaluation of 52 joints by 2 pediatric rheumatologists. Joints were assessed for swelling, tenderness/pain on motion, and restricted motion. The same joints were scanned independently by an experienced sonographer for synovial hyperplasia, joint effusion, and power Doppler (PD) signal.

Results

In total, 1,664 joints were assessed both clinically and with US. On clinical examination, 98 joints (5.9%) were swollen, 59 joints (3.5%) were tender, and 40 joints (2.4%) had restricted motion. On US evaluation, 125 joints (7.5%) had synovial hyperplasia, 153 joints (9.2%) had joint effusion, and 53 joints (3.2%) had PD signal. A total of 104 (6.3%) and 167 (10%) joints had clinical and US synovitis, respectively. Of the 1,560 clinically normal joints, 86 (5.5%) had subclinical synovitis (i.e., had synovitis on US). US led to classifying 5 patients as having polyarthritis who were classified as having oligoarthritis or were found to have no synovitis on clinical evaluation. US variables were moderately correlated with clinical measures of joint swelling, but poorly correlated with those of joint tenderness/pain on motion and restricted motion. Overall, correlations were lower for PD signal than for synovial hyperplasia and joint effusion.

Conclusion

We found that subclinical synovitis as detected by US is common in children with JIA. This finding may have important implications for patient classification and may affect the choice of the optimal therapeutic strategy in individual patients.     

Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis

Objective

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA.

Methods

Synovial fluid samples obtained from children with oligoarticular JIA, polyarticular JIA, or systemic JIA were compared. Two‐dimensional gel electrophoresis for protein separation and matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry and quadripole time‐of‐flight mass spectrometry for protein identification were used for this study. Synovial fluid cells were analyzed by polymerase chain reaction (PCR) for the presence of haptoglobin messenger RNA (mRNA).

Results

The synovial fluid proteome of the samples was delineated. The majority of proteins showed overexpression in JIA synovial fluid as compared with noninflammatory control samples. There were 24 statistically significantly differentially expressed spots (>2‐fold change; P < 0.05) between the subtypes of JIA. PCR analysis revealed haptoglobin mRNA, suggesting that haptoglobin is locally produced in an inflamed joint in JIA.

Conclusion

Despite the similar histologic appearance of inflamed joints in patients with different subtypes of JIA, there are differences in protein expression according to the subtype of JIA. Haptoglobin is differentially expressed between the subtypes of JIA and is locally produced in an inflamed joint in JIA. Haptoglobin and other differentially expressed proteins may be potential biomarkers in JIA.

     

Inherited bleeding disorders: results from the Italian Regional Haemophilia Centre of Pescara

Backgorund

Inherited bleeding disorders registries can be useful to improve health care of these rare disorders and document their natural history.

Material and methods

We analysed the epidemiological, diagnostic and therapeutic aspects of patients managed at an Italian Regional Haemophilia Centre, based in Pescara (in the Region of Abruzzo).

Results

This Regional Haemophilia Centre currently follows 376 patients: 248 with rare clotting factor defects, 33 with von Willebrand’s disease, 75 with haemophilia A and 20 with haemophilia B. Three patients with severe haemophilia A have developed inhibitors. Among all the haemophiliacs, the prevalence of hepatitis C virus infection is 21% while the prevalence of human immunodeficiency virus infection is 5.3%. Among the whole haemophilic population referring to the Pescara Haemophilia Centre, 87.4% are treated with recombinant factors while 12 patients with severe haemophilia are receiving primary prophylaxis.

Conclusion

In brief, an analysis of the epidemiological, clinical and therapeutic data collected at the Regional Haemophilia Centre of Pescara is a useful tool for monitoring and continuously improving the quality of care of patients with inherited bleeding disorders.     

Magnetic resonance imaging and miniarthroscopy of metacarpophalangeal joints: Sensitive detection of morphologic changes in rheumatoid arthritis

Objective

To evaluate and characterize magnetic resonance imaging (MRI) findings in the metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients macroscopically, using miniarthroscopy (MA; needle arthroscopy).

Methods

The second MCP joint of the dominant hand of 22 RA patients (13 with various RA activities/stages; 9 with early RA [≤1.5 years' duration]) was examined by MRI followed by MA. Findings were evaluated by standardized semiquantitative measures of synovial and bony pathologic changes of the MCP joint, and were compared with the clinical and conventional radiologic findings.

Results

Erosions and pre‐erosions were detected in 17 of 22 patients by MRI; 2 of the other 5 patients (all early RA) displayed bony changes on MA. All 10 joints with pre‐erosions on MRI (grade I bony alterations on MRI) exhibited significant cartilaginous and bony pathology on MA. Synovial membrane pathology was detected in all but 1 patient by MRI and in all patients by MA, although findings of plain radiography were normal in 6 of the 22 patients and another 9 patients had a Larsen score of 1. Semiquantitative analysis of synovial findings of MRI revealed gadolinium diethylenetriaminepentaacetic acid enhancement as a significant marker of macroscopically varied synovial vascularity and hyperemia, both of which strongly correlated with clinical activity (as measured by the Disease Activity Score). The extent of synovitis/synovial proliferation shown by MA and MRI were significantly correlated with each other, but not with any other activity or damage parameter analyzed.

Conclusion

In RA, both MRI and MA findings support early detection and staging of synovial changes. Ongoing longitudinal studies are aimed at evaluating the value of synovial proliferation as visualized by both methods.

     

Whole‐body bone scintigraphy provides a measure of the total‐body burden of osteoarthritis for the purpose of systemic biomarker validation

Objective

To evaluate the association of serum and synovial fluid cartilage oligomeric matrix protein (COMP) with systemic and local measures of osteoarthritis (OA) activity by bone scintigraphy.

Methods

Samples of serum and knee joint synovial fluid (275 knees) were obtained from 159 patients with symptomatic OA of at least 1 knee. Bone scintigraphy using ^99mTc‐labeled methylene diphosphonate was performed, and early‐phase knee scans and late‐phase whole‐body bone scans of 15 additional joint sites were scored semiquantitatively. To control for within‐subject correlations of knee data, generalized linear modeling was used in the correlation of the bone scan scores with the COMP levels. Principal components analysis was used to explore the contribution of each joint site to the variance in serum COMP levels.

Results

The correlation between synovial fluid and serum COMP levels was significant (r = 0.206, P = 0.006). Synovial fluid COMP levels correlated most strongly with the early‐phase knee bone scan scores (P = 0.0003), even after adjustment for OA severity according to the late‐phase bone scan scores (P = 0.015), as well as synovial fluid volumes (P < 0.0001). Serum COMP levels correlated with the total‐body bone scan scores (r = 0.188, P = 0.018) and with a factor composed of the bone scan scores in the shoulders, spine, lateral knees, and sacroiliac joints (P = 0.0004).

Conclusion

Synovial fluid COMP levels correlated strongly with 2 indicators of knee joint inflammation: early‐phase bone scintigraphic findings and synovial fluid volume. Serum COMP levels correlated with total‐body joint disease severity as determined by late‐phase bone scintigraphy, supporting the hypothesis that whole‐body bone scintigraphy is a means of quantifying the total‐body burden of OA for systemic biomarker validation.

     

Turning severe into moderate haemophilia by prophylaxis: are we reaching our goal?

Background

Since the introduction of prophylaxis, physicians have tried to convert the clinical phenotype of severe haemophilia (SH) into that of moderate haemophilia (MH), but the outcome of patients with SH has never been compared to that of patients with MH.

Material and methods

The outcome of 80 patients with SH on long-term, intermediate dose prophylaxis was compared to that of 40 patients with MH in a single-centre study. Data on treatment history, activities (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D), and 5-year bleeding and clotting factor consumption were collected for patients born between 1970–1995.

Results

The median age of the patients was 24 years (IQR 18–30). All patients with SH received long-term prophylaxis, which was started at a median age of 4.8 years (IQR 3.2–6.2). Among the patients with MH, ten (25%) received prophylaxis, starting at a median age of 10.8 years (IQR 3.8–13.8). The annual number of bleeds, including joint bleeds, was significantly higher in patients with SH (median 2.0 joint bleeds/year, IQR =0.8–3.7) than in patients with MH (median 0.8 joint bleeds/year, IQR =0–1.2). Due to greater use of prophylaxis, the annual clotting factor consumption of SH patients (median 2,120 IU/kg; IQR 1,514–2,768), was higher than that of MH patients (median 133 IU/kg; IQR 49–468). Patients with SH showed slightly but significantly more loss of clinical function (assessed by the Haemophilia Joint Health Score): a median of 8 points (IQR 3–15) vs a median of 2 points, IQR 0–6). Quality of life, as measured by the SF-36, EQ5D and physical activity, was similar between patients with disease of different severity, as well as compared to that of the general population.

Discussion

When comparing unselected cohorts, the bleeding pattern of patients with SH does not appear to be fully converted to that of the milder bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although activities and quality of life were similar.     

Multiple joint involvement in total knee replacement for osteoarthritis: Effects on patient‐reported outcomes

Objective

To determine whether symptomatic (painful/problematic) joints pre–total knee replacement (TKR) surgery influence 1) pre‐ and 12‐month post‐TKR patient‐reported outcomes (pain, physical function, and mood [fatigue, anxiety, and depression]) and 2) postsurgical pain and function mediated through mood.

Methods

A total of 494 participants completed the patient‐reported outcome measures pre‐ and 12‐months post‐TKR. Symptomatic (painful/problematic) joints affected by arthritis were indicated on a homunculus presurgery. Covariate data included age, sex, educational attainment, body mass index, and comorbidity. Pre‐ and postsurgical outcome scores were regressed on symptomatic joint sites and covariates using linear regression analyses; postsurgical scores additionally were regressed on presurgery scores. Path analyses examined whether the effects of symptomatic joint sites on postsurgical pain and function were mediated through mood.

Results

The age range was 35–88 years (mean 65 years) and 65% were women. Forty‐six percent reported ≥4 symptomatic joints (other than the surgical knee). Pre‐ and postsurgery, worse outcome scores were observed with increasing joint count. Adjusted for covariates, individuals reporting symptomatic ankles/feet/toes, neck, and spine/lower back had worse presurgery fatigue and anxiety. Adjusted for covariates and presurgery status, worse fatigue for the neck and spine/lower back and worse depression, pain, and function for the ankles/feet/toes and neck were observed postsurgery. The influence of symptomatic ankles/feet/toes on postsurgical pain and function was in part direct and partially mediated through depression. Full mediation was found for the neck through fatigue, anxiety, and depression, and for the spine/lower back through fatigue.

Conclusion

Findings suggest that a comprehensive approach to osteoarthritis management/care is warranted, and identify important associations between symptomatic joints and mood that negatively impact post‐TKR pain and physical function.