Francesca Faustini

Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies

Objective Anticitrullinated protein antibodies (ACPA) are a major risk factor for bone loss in rheumatoid arthritis (RA). We have recently shown that ACPA directly induce bone loss by stimulating osteoclast differentiation. As ACPA precede the clinical onset of RA by years, we hypothesised that ACPA positive healthy individuals may already show skeletal changes. Methods We performed a comparative micro-CT analysis of the bone microstructure in the metacarpophalangeal joints of ACPA positive and ACPA negative healthy individuals without clinical signs of arthritis. Results ACPA positive (n=15) and negative (n=15) healthy individuals were not different in age (48.2±4.1 vs 51.4±3.8 years, p=0.57) or gender (eight women and two men in both groups). Bone mineral density was significantly reduced in ACPA positive individuals (mean±SEM 280±11 mg/cm3) compared with controls (327±6). Bone loss was based on cortical bone changes, with significant (p=0.044) reduction in cortical thickness in the ACPA positive group (mean±SEM 0.22±0.03 mm) compared with controls (0.32±0.03 mm). Areas of cortical porosity were significantly (p=0.0005) more widespread in ACPA positive (mean±SEM 7.4±1.4%) than in ACPA negative individuals (1.0±0.3%). Discussion Structural bone damage starts before the clinical onset of arthritis in subjects with ACPA. These findings revise the concept that bone damage is an exclusive consequence of synovitis in patients with RA.

Tophus resolution with pegloticase: a prospective dual-energy CT study

Objective To investigate the effect of intensive lowering of serum uric acid (SUA) levels by pegloticase on the resolution of tophi in patients with refractory gout. Methods Descriptive study in patients with refractory gout receiving pegloticase treatment. SUA levels were measured before and after each infusion. Dual-energy CT (DECT) scans were taken from all patients before the first infusion and after the last infusion. Computerised tophus volumes were calculated for the baseline and follow-up assessments and compared with each other. Results 10 patients with refractory gout and baseline mean SUA level of 8.1 mg/dL were enrolled. Patients were treated for a mean of 13.3 weeks. Pegloticase effectively reduced tophi in all patients showing a decrease in volume by 71.4%. Responders, showing reduction of SUA level below 6 mg/dL during at least 80% of the treatment time, were virtually cleared from tophi (−94.8%). Dependent on their anatomical localisation, resolution of tophi showed different dynamics, with articular tophi showing fast, and tendon tophi slow, resolution. Conclusions Tophi are highly sensitive to pegloticase treatment, particularly when located at articular sites. Debulking of disease and a tophus-free state can be reached within a few months of pegloticase treatment. DECT allows for comprehensively assessing tophus burden and monitoring treatment responses.

High incidence of disease recurrence after discontinuation of disease-modifying antirheumatic drug treatment in patients with psoriatic arthritis in remission

Objective To investigate the possibility of drug-free remission in patients with psoriatic arthritis (PsA) in continuous remission. Methods Prospective observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA patients in continuous disease remission (no musculoskeletal symptoms, no or minimal skin/nail disease) for at least 6 months. Demographic, disease-specific and ultrasound parameters were assessed at baseline. DMARDs (traditional or biologic) were discontinued at the initial visit, and patients were followed for a maximum of 6 months for recurrence of disease. Results 26 patients (methotrexate monotherapy: N=14; tumour necrosis factor inhibitors: N=12) with a mean age of 55.2 years, absence of musculoskeletal symptoms and minimal skin disease (mean Psoriasis Area Severity Index (PASI): 0.21) were enrolled. Incidence of recurrence of disease was high (N=20, 76.9%) and occurred rapidly (74.50±51.72 days) after treatment discontinuation. Male PsA patients were significantly more likely to lose remission. Long disease duration, more severe skin involvement and the presence of synovial hypertrophy by ultrasonographic examination at baseline decreased the likelihood for drug-free remission. Reinitiation of DMARDs promptly restored remission in all PsA patients with recurrence of disease. Conclusions This study shows that the chance to reach drug-free remission in PsA patients is low. Discontinuation of DMARD therapy cannot be recommended in patients with PsA.

Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis

Objectives To search for structural bone changes in the joints of psoriasis patients without psoriatic arthritis (PsA). Methods 55 psoriasis patients without any current or past symptoms of arthritis or enthesitis and 47 healthy controls were examined by high-resolution peripheral quantitative CT scans of the metacarpophalangeal joints. Number, size and exact localisation of erosions and enthesiophytes were recorded by analysing axial scans of the metacarpal heads and phalangeal bases and were confirmed in additional coronal and/or sagittal sections. In addition, we collected demographic and clinical data including subtype, duration and severity of psoriasis. Results Psoriasis patients showed a larger and significantly increased number of enthesiophytes (total number 306; mean±SD/patient 5.62±3.30) compared with healthy controls (total number 138; mean±SD/patient 3.04±1.81, p<0.001). Enthesiophytes were typically found at the dorsal and palmar sides of the metacarpal heads where functional entheses related to extensor and flexor tendons are localised. Bone erosions were rare and not significantly different between psoriasis patients and healthy controls. If present, erosions were almost exclusively found at the radial side of the second metacarpal head in both psoriasis patients and healthy controls. Conclusions Psoriasis patients without PsA show substantial signs of enthesiophyte formation compared with healthy controls. These changes represent new bone formation at mechanically exposed sites of the joint and substantiate the concept of the existence of a ‘Deep Koebner Phenomenon’ at enthesial sites in psoriasis patients.

Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis

Objectives To search for subclinical inflammatory joint disease in patients with psoriasis without psoriatic arthritis (PsA), and to determine whether such changes are associated with the later development of PsA. Methods Eighty-five subjects without arthritis (55 with psoriasis and 30 healthy controls) received high field MRI of the hand. MRI scans were scored for synovitis, osteitis, tenosynovitis and periarticular inflammation according to the PsAMRIS method. Patients with psoriasis additionally received complete clinical investigation, high-resolution peripheral quantitative CT for detecting erosions and enthesiophytes and were followed up for at least 1 year for the development of PsA. Results 47% of patients with psoriasis showed at least one inflammatory lesion on MRI. Synovitis was the most prevalent inflammatory lesion (38%), while osteitis (11%), tenosynovitis (4%) and periarticular inflammation (4%) were less frequent. The mean (±SD) PsAMRIS synovitis score was 3.0±2.5 units. Enthesiophytes and bone erosions were not different between patients with psoriasis with or without inflammatory MRI changes. The risk for developing PsA was as high as 60% if patients had subclinical synovitis and symptoms related to arthralgia, but only 13% if patients had normal MRIs and did not report arthralgia. Conclusions Prevalence of subclinical inflammatory lesions is high in patients with cutaneous psoriasis. Arthralgia in conjunction with MRI synovitis constitutes a high-risk constellation for the development of PsA.

A comparative analysis of magnetic resonance imaging and high-resolution peripheral quantitative computed tomography of the hand for the detection of erosion repair in rheumatoid arthritis

OBJECTIVES To investigate whether MRI allows the detection of osteosclerosis as a sign of repair of bone erosions compared with high-resolution peripheral quantitative computed tomography (HR-pQCT) as a reference and whether the presence of osteosclerosis on HR-pQCT is linked to synovitis and osteitis on MRI. METHODS A total of 103 RA patients underwent HR-pQCT and MRI of the dominant hand. The presence and size of erosions and the presence and extent (grades 0-2) of osteosclerosis were assessed by both imaging modalities, focusing on MCP 2 and 3 and wrist joints. By MRI, the presence and grading of osteitis and synovitis were assessed according to the Rheumatoid Arthritis MRI Score (RAMRIS). RESULTS Parallel evaluation was feasible by both modalities on 126 bone erosions. Signs of osteosclerosis were found on 87 erosions by HR-pQCT and on 22 by MRI. False-positive results (MRI(+)CT(-)) accounted for 3%, while false-negative results (MRI(-)CT(+)) accounted for 76%. MRI sensitivity for the detection of osteosclerosis was 24% and specificity was 97%. The semi-quantitative scoring of osteosclerosis was reliable between MRI and HR-pQCT [intraclass correlation coefficient 0.917 (95% CI 0.884, 0.941), P < 0.001]. The presence of osteosclerosis on HR-pQCT showed a trend towards an inverse relationship to the occurrence and extent of osteitis on MRI [χ(2)(1) = 3.285; ϕ coefficient = -0.124; P = 0.070] but not to synovitis [χ(2)(1) = 0.039; ϕ coefficient = -0.14; P = 0.844]. CONCLUSION MRI can only rarely detect osteosclerosis associated with bone erosions in RA. Indeed, the sensitivity compared with HR-pQCT is limited, while the specificity is high. The presence of osteitis makes osteosclerosis more unlikely, whereas the presence of synovitis is not related to osteosclerosis.

High prevalence of tenosynovial inflammation before onset of rheumatoid arthritis and its link to progression to RA—A combined MRI/CT study

OBJECTIVE To define the anatomic distribution of the earliest inflammatory and structural changes in individuals with anti-citrullinated protein antibody (ACPA+) positivity but no signs of arthritis. METHODS ACPA+ individuals (N = 20) and healthy controls (N = 13) received simultaneous gadolinium-enhanced magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the hands. MRI sequences were scored for synovitis, osteitis, and bone erosions according to the RAMRIS method as well as for presence, localization, and extent of tenosynovitis. Bone erosions were validated by HR-pQCT scanning and related to the inflammatory changes found in the MRI. RESULTS Tenosynovitis was the most prevalent inflammatory pathology, affecting 80% of ACPA+ individuals but none of the controls. Tenosynovitis at two or more anatomical sites was associated with later development of RA. Synovitis (65%) and osteitis (35%) were present in ACPA+ individuals as well, but at a lower frequency than tenosynovitis. MRI bone erosions were found in 65% of the individuals and additionally confirmed by HR-pQCT. Presence of MRI osteitis was the inflammatory pathology most strongly associated with bone erosions. CONCLUSION Tenosynovitis is highly prevalent in ACPA+ individuals without arthritis and associated with later development of RA. Small erosions, often linked to osteitis, are also found in ACPA+ individuals without arthritis.

High-resolution Quantitative Computed Tomography Demonstrates Structural Defects in Cortical and Trabecular Bone in IBD Patients.

BACKGROUND AND AIMS To investigate the macro- and microstructural changes of bone in patients with inflammatory bowel disease [IBD] and to define the factors associated with bone loss in IBD. METHODS A total of 148 subjects, 59 with Crohns disease [CD], 39 with ulcerative colitis [UC], and 50 healthy controls were assessed for the geometric, volumetric and microstructural properties of bone using high-resolution peripheral quantitative computed tomography. In addition, demographic and disease-specific characteristics of IBD patients were recorded. RESULTS IBD patients and controls were comparable in age, sex, and body mass index. Total [p = 0.001], cortical [p < 0.001], and trabecular volumetric bone mineral density [BMD] [p = 0.03] were significantly reduced in IBD patients compared with healthy controls. Geometric and microstructural analysis revealed significantly lower cortical area [p = 0.001] and cortical thickness [p < 0.001] without differences in cortical porosity, pore volume, or pore diameter. CD showed a more severe bone phenotype than UC: cortical bone loss was observed in both diseases, but CD additionally showed profound trabecular bone loss with reduced trabecular BMD [p = 0.008], bone volume [p = 0.008], and trabecular thickness [p = 0.009]. Multivariate regression models identified the diagnosis of CD, female sex, lower body mass index, and the lack of remission as factors independently associated with bone loss in IBD. CONCLUSION IBD patients develop significant cortical bone loss, impairing bone strength. Trabecular bone loss is limited to CD patients, who exhibit a more severe bone phenotype compared with UC patients.

SAT0182 Magnetic Resonance Imaging (MRI) of Hands of Psoriasis Patients: High Incidence of Inflammation

Background Patients with cutaneous psoriasis (PSO) are at risk of developing psoriatic arthritis (PsA) overtime. The transition from skin disease to joint involvement is only partially characterized. Advanced imaging can depict signs of subclinical joint involvement. Objectives To assess the prevalence of inflammatory MRI signs in a group of PSO patients with no history or presence of PsA, who showed bony changes (either erosions or osteophytes) on high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondly, to examine whether inflammation on MRI is linked to the changes on HR-pQCT. Methods PSO patients (with no arthritis, enthesitis nor dactylitis) underwent HR-pQCT and 1.5T magnetic resonance imaging (MRI) of the dominant hand. HR-pQCT scanning was conducted on the metacarpophalangeal (MCP) joints 2 and 3. Images were analyzed for the presence of periarticular changes as erosions and osteophytes. MRI images were acquired for the whole hand. Subsequent analysis of the images focused on the detection of osteitis, synovitis, tenosynovitis of the flexor tendon, periarticular inflammation at the MCP, PIP and DIP region of the 2nd to 5th finger, according to the definitions of key pathologies provided for the PsAMRIS scoring system.1 HR-pQCT and MRI images have been analyzed by 2 independent readers, mean time interval between both imaging techniques was 42 days. The study was conducted upon approval by the local ethic committee and the National Radiation Safety Agency (BfS). Patients participated after signing informed consent. Results Images were acquired from 55 PSO patients (36.4% female) of mean age 49.5±11.5 years, mean disease duration 15.2±15.4 years and mean PASI score of 6.2±8.0. The most prevalent subtype was psoriasis vulgaris (73%), while nail psoriasis was present in 51% and scalp involvement in 29%. By HR-pQCT, 29% of the patients showed erosions, while all presented osteophytes. Of the 55 patients, 26 (47%) showed at least one of the mentioned inflammatory signs on MRI. In detail, osteitis was found in 6 out of the 55 patients (11%), while synovitis in 21 (38%); tenosynovitis and periarticular inflammation were detected each in 2 patients (4%). In the total sample, partial correlations (controlling for the influence of age and disease duration) between bony changes in HR-pQCT and osteitis as well as synovitis in MRI did not show any significant relations. Conclusions Subclinical inflammatory lesions are prevalent in the joints of patients with PSO and affect about half of the patients. These findings suggest that a substantial proportion of PSO patients are affected by joint inflammation but are not classified as PsA. Interestingly, the relation of inflammatory-MRI changes to structural-CT changes in the joints of PSO patients is rather poor at the cross-sectional level, which will necessitate longitudinal assessment of joint inflammation in PSO patients. References Ostergaard M et al, J Rheumatol. 2009 Aug; 36(8): 1816-24 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5412

Simultaneous quantification of bone erosions and enthesiophytes in the joints of patients with psoriasis or psoriatic arthritis - effects of age and disease duration

BackgroundComprehensive simultaneous quantification of bone erosion and enthesiophytes in the joints of patients with psoriatic arthritis (PsA) has not been performed. Herein, we aimed to compare the extent of bone erosion and enthesiophytes in patients with PsA, psoriasis (PSO) and healthy controls, assess the influence of age and disease duration on the development of erosions and enthesiophytes and define their impact on physical function.MethodsPatients with PsA or with PSO and controls were analysed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The extent of bone erosions and enthesiophytes was assessed and plotted according to different categories of age, duration of PSO and duration of PsA, respectively. In addition, demographic and disease-specific data, including physical function (health assessment questionnaire) were collected.ResultsA total of 203 patients were analysed; 101 had PsA, 55 had PSO and 47 were healthy individuals. Patients with PsA had significantly more and larger erosions (p = 0.002/p = 0.003) and enthesiophytes (p < 0.001) compared to patients with PSO and healthy controls. Patients with PSO and healthy controls did not differ in erosions, while enthesiophytes were more frequent in patients with PSO than in healthy controls. Bone erosions, but not enthesiophytes, showed strong age-dependency in all three groups. In contrast, enthesiophytes were mostly influenced by the duration of PSO and PsA and, in contrast to bone erosions, were associated with poorer physical function.ConclusionsBone erosions are age-dependent, enhanced in PsA and increase with disease duration. Enthesiophytes are less age-dependent, are enhanced in both PSO and PsA and strongly influenced by disease duration. Enthesiophytes impact physical function in PsA suggesting the need for early therapeutic interventions to prevent damage.