David Simon

Quantitative and qualitative changes of bone in Psoriasis and Psoriatic Arthritis patients

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by periarticular bone loss and new bone formation. Current data regarding systemic bone loss and bone mineral density (BMD) in PsA are conflicting. The aim of this study was to evaluate bone microstructure and volumetric BMD (vBMD) in patients with PsA and psoriasis. We performed HR‐pQCT scans at the ultradistal and periarticular radius in 50 PsA patients, 30 psoriasis patients, and 70 healthy, age‐ and sex‐related controls assessing trabecular bone volume (BV/TV), trabecular number (Tb.N), inhomogeneity of the trabecular network, cortical thickness (Ct.Th), and cortical porosity (Ct.Po), as well as vBMD. Trabecular BMD (Tb.BMD, p = 0.021, 12.0%), BV/TV (p = 0.020, –11.9%), and Tb.N (p = 0.035, 7.1%) were significantly decreased at the ultradistal radius and the periarticular radius in PsA patients compared to controls. In contrast, bone architecture of the ultradistal radius and periarticular radius was similar in patients with psoriasis and healthy controls. Duration of skin disease was associated with low BV/TV and Tb.N in patients with PsA. These data suggest that trabecular BMD and bone microstructure are decreased in PsA patients. The observation that duration of skin disease determines bone loss in PsA supports the concept of subclinical musculoskeletal disease in psoriasis patients.

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.

Age- and Sex-Dependent Changes of Intra-articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis.

The objective of this cross‐sectional study was to define normal sex‐ and age‐dependent values of intra‐articular bone mass and microstructures in the metacarpal heads of healthy individuals by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra‐articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR‐pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra‐articular (intracapsular) bone margins. These data were applied in measuring intra‐articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra‐articular and radial bone parameters were good (r = 0.51 to 0.62, p < 0.001). In contrast to radial bone, intra‐articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm3) but decreased significantly (p < 0.001) in women thereafter (237.5 ± 44.3) with loss of both cortical and trabecular bone. Similarly, RA patients showed significant (p < 0.001) loss of intra‐articular total (263.0 ± 44.8), trabecular (171.2 ± 35.6), and cortical bone (610.2 ± 62.0) compared with sex‐ and age‐adjusted controls. Standard sex‐ and age‐dependent values for physiological intra‐articular bone were defined. Postmenopausal state and RA led to significant decrease of intra‐articular bone.

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.

Rheumatoid arthritis is characterized by early changes of the cortical micro-channel (CoMiC) system in the bare area of the joints

To characterize the specific structural properties of the erosion‐prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA).Objective: To characterize the specific structural properties of the erosion-prone bare area of the human joint and to search for early microstructural changes in this region during rheumatoid arthritis Methods: An initial cadaveric study was used for exact localization of the bare area of the metacarpal heads, detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral computed tomography (HR-pQCT) and, after anatomical dissection, their validation by micro-computed tomography (μCT). In the second part, number and distribution of CoMiCs were analyzed in 105 healthy individuals and 107 RA patients with similar sex and age distribution. Results: HR-pQCT investigation combined with adaptive thresholding allowed detection of CoMiCs in the bare area of cadaveric joints. Their existence in the bare area was additionally validated by μCT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly (p<0.001) more CoMiCs (112.9±54.7/joint) than healthy individuals (75.2±41.9/joint) with 20-49 years old RA patients exhibiting similar CoMiC numbers as observed in over 65 year old healthy individuals. Importantly, CoMiCs were found in RA patients already very early in their disease course with enrichment in the erosion-prone radial side of the joint. Conclusion: CoMiCs represent a new form of structural change in the joints of patients with RA. While CoMiCs increase with age, RA patients develop such changes much earlier in life and already at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA. This article is protected by copyright. All rights reserved.

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.

Cutting Edge: Homeostasis of Innate Lymphoid Cells Is Imbalanced in Psoriatic Arthritis

Innate lymphoid cells (ILC) have a high potency for cytokine production independent of specific Ag stimulation. Imbalance of ILC subsets may influence cytokine production in humans and hence be associated with the development of inflammatory disease. Evidence for an imbalance of ILC homeostasis in human disease, however, is very limited to date. In this study we show that psoriatic arthritis (PsA), a severe disease of the joints depending on the activation of the IL-23/IL-17 pathway, is characterized by a skewed ILC homeostasis. Circulating ILC3s as potent source of IL-17/IL-22 were elevated in active PsA, whereas ILC2s, which produce proresolving cytokines, were decreased. The ILC2/ILC3 ratio was significantly correlated with clinical disease activity scores and the presence of imaging signs of joint inflammation and bone damage. Multivariable analysis showed that a high ILC2/ILC3 ratio is associated with remission in PsA, suggesting that specific alterations of ILC homeostasis control disease activity in PsA.

Quantification and Impact of Secondary Osteoarthritis in Patients With Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis

To search for evidence of secondary osteoarthritis (OA) in patients with rheumatoid arthritis (RA) in a cross‐sectional and longitudinal setting, and to relate osteophyte formation to functional outcome.

Methods for segmentation of rheumatoid arthritis bone erosions in high-resolution peripheral quantitative computed tomography (HR-pQCT)

OBJECTIVE The comparison between different techniques to quantify the 3-dimensional size of inflammatory bone erosions in rheumatoid arthritis(RA) patients. METHODS Anti-cyclic citrullinated peptide antibody(ACPA) positive RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the metacarpophalangeal joints (MCP). Erosions were measured by three different segmentation techniques: (1) manual method with calculation by half-ellipsoid formula, (2) semi-automated modified Evaluation Script for Erosions (mESE), and (3) semi-automated Medical Image Analysis Framework (MIAF) software. Bland & Altman plots were used to describe agreement between methods. Furthermore, shape of erosions was classified as regular or irregular and then compared to the sphericity obtained by MIAF. RESULTS A total of 76 erosions from 65 RA patients (46 females/19 males), median age 57 years, median disease duration 6.1 years and median disease activity score 28 of 2.8 units were analyzed. While mESE and MIAF showed good agreement in the measurement of erosion size, the manual method with calculation by half-ellipsoid formula underestimated erosions size, particularly with larger erosions. Accurate segmentation is particularly important in larger erosions, which are irregularly shaped. In all three segmentation techniques irregular erosions were larger in size than regular erosions (MIAF: 19.7 vs. 3.4mm3; mESE: 15.5 vs. 2.3mm3; manual = 7.2 vs. 1.52mm3; all p < 0.001). In accordance, sphericity of erosions measured by MIAF significantly decreased with their size (p < 0.001). CONCLUSION MIAF and mESE allow segmentation of inflammatory bone erosions in RA patients with excellent inter reader reliability. They allow calculating erosion volume independent of erosion shape and therefore provide an attractive tool to quantify structural damage in individual joints of RA patients.