B. Ostendorf

Preliminary results of safety and efficacy of the interleukin-1 receptor antagonist anakinra in patients with severe lupus arthritis

Background: Joint involvement occurs in most patients with systemic lupus erythematosus (SLE), and severe lupus arthritis is often refractory to conventional treatments. Anakinra is used in the treatment of rheumatoid arthritis, but its therapeutic potential has not been proved in patients with SLE. Objective: To determine the safety/tolerability and efficacy of anakinra in patients with SLE with leading joint involvement. Methods: In patients with SLE with active polyarthritis and no other uncontrolled systemic/organ manifestations, 100 mg/day anakinra was self administered subcutaneously for 3 months. Disease activity was assessed by VAS, number of swollen/tender joints, ECLAM score, and serological and immunological measures. Results: Four patients with SLE were studied; anakinra was safe in all four patients and no drug related serious adverse events occurred. A subjective benefit was seen in all patients and a trend towards better activity measures after 4 weeks. After an initial response, one patient left the study because of an arthritic flare after 6 weeks. Conclusion: In this study anakinra was apparently safe and well tolerated and led to clinical and serological improvement. Anakinra might be an interesting alternative in individual patients with lupus arthritis not responding to conventional treatments.

What is MRI bone oedema in rheumatoid arthritis and why does it matter

MRI bone oedema occurs in various forms of inflammatory and non-inflammatory arthritis and probably represents a cellular infiltrate within bone. It is common in early rheumatoid arthritis and is associated with erosive progression and poor functional outcome. Histopathological studies suggest that a cellular infiltrate comprising lymphocytes and osteoclasts may be detected in subchondral bone and could mediate the development of erosions from the marrow towards the joint surface. There is emerging evidence from animal models that such an infiltrate corresponds with MRI bone oedema, pointing towards the bone marrow as a site for important pathology driving joint damage in rheumatoid arthritis.

Hybrid 18F-FDG PET-MRI of the hand in rheumatoid arthritis: initial results.

Abstract18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET–MRI examination of the hand in early RA exploiting the advantages of both modalities. PET–MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET–MRI of the hand is technically feasible and bears the potential to directly visualize inflammation.

Bildgebende Verfahren in der Rheumatologie: Magnetresonanztomographie bei Rheumatoider Arthritis

Zusammenfassung. Die Magnetresonanztomographie (MRT) stellt zur Zeit das modernste und zugleich technisch aufwendigste Schnittbildverfahren der Radiologie dar. Die MRT zeichnet sich dabei gegenüber anderen bildgebenden Verfahren durch einen überlegenen Weichteilkontrast, die Möglichkeit der multiplanaren Darstellung und das Fehlen ionisierender Strahlen aus. Durch adäquate Differenzierung und Abbildung von Weichteil- und knöchernen Veränderungen gewinnt sie bei der Frühdiagnostik und Verlaufskontrolle entzündlich-rheumatischer Gelenkerkrankungen, wie z. B. der Rheumatoiden Arthritis (RA), immer mehr an Bedeutung. Deshalb kommt nicht nur der technischen Qualitätssicherung, sondern vor allem auch der ärztlichen Qualifikation bei der Indikationsstellung, der Durchführung als auch der Auswertung der MRT eine besondere Rolle zu. Diese Entwicklung verlangt daher für den Einsatz der MRT in der Rheumatologie standardisierte Empfehlungen und Untersuchungsprotokolle, welche von Rheumatologen und Radiologen der Kommission “bildgebende Verfahren” der Deutschen Gesellschaft für Rheumatologie (DGRh) zusammengefasst und vorgestellt werden.Summary. Magnetic resonance imaging (MRI) is currently the most modern and, at the same time, most technically advanced instrument of sectional imaging in diagnostic radiology. MRI is superior to other radiological procedures because of its excellent soft-tissue contrast, the possibility of multiplanar imaging and the missing of ionizing radiation. Exact differentiation and imaging of soft tissue and bony alterations is of significant evidence in early diagnosis and monitoring of inflammatory joint diseases, such as rheumatoid arthritis (RA). Besides securing of technical quality management, the physicians qualification in indication, conduction and evaluation of MRI plays a pivotal role. This development of MRI for rheumatological purposes needs standardized recommendations and investigation protocols, which are now summarized and presented by the rheumatologists and radiologists of the study group of “diagnostic imaging procedures” of the German Society for Rheumatology (DGRh).

Early detection of bony alterations in rheumatoid and erosive arthritis of finger joints with high-resolution single photon emission computed tomography, and differentiation between them

ObjectiveTo evaluate high-resolution multi-pinhole single photon emission computed tomography (MPH-SPECT) for the detection of bony alterations in early rheumatoid arthritis (ERA), early osteoarthritis (EOA) of the fingers and healthy controls.MethodsThe clinically dominant hands of 27 patients (13 ERA, nine EOA, five healthy controls) were examined by MPH-SPECT and bone scintigraphy. Additionally, magnetic resonance imaging (MRI) was performed in the ERA patients. Number of affected joints, localisation, pattern of tracer distribution and joint involvement were scored. Quantitative analysis was achieved by measurement of the region of interest (ROI) in all patients. The MPH-SPECT and MR images were fused in the ERA group.ResultsBone scintigraphy detected fewer joints (26 joints,13/22 patients) with increased tracer uptake than did MPH-SPECT (80 joints, 21/22 patients). Bone scintigraphy did not show recognisable uptake patterns in any group of patients. With MPH-SPECT central tracer distribution was typical in ERA (10/13 patients, EOA 2/9). In contrast, an eccentric pattern was found predominantly in EOA (7/9, ERA 2/13). Normalised counts were 4.5 in unaffected joints and up to 222.7 in affected joints. The mean uptake values in affected joints were moderately higher in the EOA patients (78.75, and 62.16 in ERA). The mean tracer uptake in affected joints was approximately three-times higher than in unaffected joints in both groups (ERA 3.64-times higher, EOA 3.58). Correlation with MR images revealed that bone marrow oedema and erosions matched pathological tracer accumulation of MPH-SPECT in 11/13. MPH-SPECT demonstrated increased activity in 2/13 patients with normal bone marrow signal intensity and synovitis seen on MR images.ConclusionMPH-SPECT is sensitive to early changes in ERA and EOA and permits them to be distinguished by their patterns of uptake.

Molecular imaging of cartilage damage of finger joints in early rheumatoid arthritis with delayed gadolinium-enhanced magnetic resonance imaging.

OBJECTIVE To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers. METHODS After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25-66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartilage thickness and delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index (T1 [msec]) were obtained using the variable flip-angle method and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis (using the RA MRI Scoring criteria). Students t-test was used to test the significance of differences between groups. RESULTS The mean ± SD dGEMRIC index was 497 ± 86 msec in healthy volunteers and was significantly lower in the early RA group (421 ± 76 msec) (P = 0.042). There was no joint space narrowing seen on standard radiographs. No significant difference was found between cartilage thickness in patients with early RA and that in controls (index finger mean ± SD 1.27 ± 0.23 mm in RA patients versus 1.46 ± 0.34 mm in controls [P = 0.16] and middle finger 1.26 ± 0.23 mm in RA patients versus 0.97 ± 0.47 mm in controls [P = 0.10]). No significant correlation was noted between cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R = 0.156, P = 0.445 in controls). CONCLUSION Our findings indicate that cartilage damage is present in the MCP joints of patients with early RA despite the absence of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA can be imaged with dGEMRIC.

Metacarpophalangeal Joints in Rheumatoid Arthritis: Delayed Gadolinium-enhanced MR Imaging of Cartilage—A Feasibility Study

PURPOSE To evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance (MR) imaging of the cartilage of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA) compared with that in control subjects. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Thirty-one MCP joints in 10 patients with RA (mean age, 59 years; range, 35-77 years) and six healthy volunteers (mean age, 51 years; range, 30-71 years) were examined with delayed gadolinium-enhanced MR imaging of cartilage. Sagittal images of the second and third MCP joints (hereafter, MCP II and MCP III) were acquired with a three-dimensional dual-flip-angle gradient-echo sequence at 3.0 T. B(1) field inhomogeneity-corrected T1 maps were calculated, and delayed gadolinium-enhanced MR imaging of cartilage values for phalangeal and metacarpal cartilage were determined. In addition, cartilage thickness was measured. A nonparametric Mann-Whitney U test was used to assess differences between groups. RESULTS Phalangeal and metacarpal delayed gadolinium-enhanced MR imaging of cartilage values in patients with RA (MCP II: 388 msec ± 105 [standard deviation] and 342 msec ± 79, respectively; MCP III: 409 msec ± 96 and 371 msec ± 89, respectively) were significantly lower than in control subjects (MCP II: 598 msec ± 62 and 560 msec ± 51, respectively; MCP III: 586 msec ± 57 and 561 msec ± 80, respectively). Cartilage thickness of both joints was comparable in patients with RA (MCP II: 1.28 mm ± 0.50, MCP III: 1.17 mm ± 0.24) and control subjects (MCP II: 1.42 mm ± 0.33, MCP III: 1.18 mm ± 0.26). CONCLUSION Delayed gadolinium-enhanced MR imaging of cartilage of the MCP joints is feasible at 3.0 T. Delayed gadolinium-enhanced MR imaging of cartilage may help to assess cartilage degeneration in morphologically normal-appearing MCP II and III cartilage in patients with RA.

T lymphocytes in patients with primary vasculitis: expansion of CD8+ T cells with the propensity to activate polymorphonuclear neutrophils

OBJECTIVES To gain insight into the immune pathogenesis of primary ANCA-associated vasculitides, the prevalence of circulating T lymphocytes expressing CD11b as a marker for activation was analysed in patients with WG or microscopic polyangiitis. METHODS; Receptor expression and IFNgamma synthesis were measured in T cells of patients with active disease by cytofluorometry and compared with expression in patients in remission and in healthy donors. RESULTS During active disease, a small but conspicuous population of CD8+CD28+CD11b+ was found which produced IFNgamma. In healthy donors and in patients in remission or undergoing immunosuppressive therapy, CD11b was exclusively associated with CD8+CD28- cells, the latter being more frequent in patients with long-lasting or severe disease. In vitro experiments confirmed that CD11b is up-regulated when T cells are activated. After multiple rounds of restimulation, the CD11b expression persists whereas CD28 expression is lost, compatible with the notion that CD8+CD28+CD11b+ represents a transient phenotype in the course of T-cell activation. The IFNgamma-producing T cells activated polymorphonuclear neutrophils (PMN) to express MHC class II, thus generating the same PMN phenotype as in patients with active ANCA-associated vasculitis. A similar PMN phenotype could be generated by cultivation with supernatants of activated T cells or by IFNgamma alone, but not by antibodies to proteinase 3. CONCLUSIONS In active primary vasculitis, a small population of CD8+ T cells, identified by the expression of CD11b, expands, producing IFNgamma. These T cells could activate PMN, thus generating a long-living and potentially destructive PMN phenotype.

Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis

To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with spondyloarthritis (SpA) using glycosaminoglycan chemical exchange saturation transfer (gagCEST).

Dynamic contrast-enhanced magnetic resonance imaging of metacarpophalangeal joints reflects histological signs of synovitis in rheumatoid arthritis

IntroductionSynovial inflammation and joint destruction in rheumatoid arthritis (RA) may progress despite clinical remission. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to detect synovial inflammation in RA. Although small joints such as metacarpophalangeal (MCP) joints are mainly affected by RA, MRI findings have never been directly compared to histological synovitis in MCP synovial tissue. The objective of the current study was therefore to analyse if DCE-MRI relates to histological signs of synovitis small RA joints.MethodsIn 9 RA patients, DCE-MRI (3 Tesla, dynamic 2D T1 weighted turbo-flash sequence) of the hand was performed prior to arthroscopically-guided synovial biopsies from the second MCP of the imaged hand. Maximum enhancement (ME), rate of early enhancement, and maximum rate of enhancement were assessed in the MCP. Synovial biopsies were stained for determination of sublining CD68 and the Synovitis Score. Correlations between MRI and histological data were calculated according to Spearman.ResultsME of the MCP significantly correlated to sublining CD68 staining (r = 0.750, P = 0.02), the Synovitis Score (r = 0.743, P = 0.02), and the subscores for lining layer hypertrophy (r = 0.789, P = 0.01) and cellular density (r = 0.842; P = 0.004).ConclusionsPerfusion imaging of synovial tissue in RA finger joints employing DCE-MRI reflects histological synovial inflammation. According to our study, ME is the most closely associated parameter amongst the measures considered.