The "green nail" phenomenon in ICG-enhanced fluorescence optical imaging - a potential tool for the differential diagnosis of psoriatic arthritis.

BACKGROUND AND OBJECTIVES: Early diagnosis of psoriatic arthritis poses a particular challenge. A novel fluorescence optical imaging technique, the Xiralite® system is very useful in this regard as it allows for visualization of microvasculature and perfusion. The present study is the first to systematically examine fluorescence optical signals in a large psoriatic arthritis cohort. PATIENTS AND METHODS: In the primary study, we reviewed and analyzed extra-articular fluorescence optical signal patterns in 241 imaging sequences obtained from 187 psoriatic arthritis patients; 36 fluorescence optical sequences from 31 patients with rheumatoid arthritis served as controls. In a follow-up study, 203 consecutive fluorescence optical sequences from 54 psoriatic arthritis patients and 149 control subjects with various inflammatory rheumatic disorders were retrospectively evaluated in order to validate the primary study results in terms of the patterns previously identified. RESULTS: Psoriatic arthritis patients exhibited three different fluorescence optical signal patterns in projection of the nails that have not been previously described. One of these patterns was the "green nail" sign, which was highly specific (97 %) for psoriatic arthritis. In the follow-up study, the specificity of this phenomenon in psoriatic arthritis was 87 % in comparison to the control cohort. CONCLUSIONS: In the present study, fluorescence optical signals in the nail region proved to be highly specific for psoriatic arthritis. The "green nail" phenomenon seems to be of particular diagnostic interest as a potential sign of impaired microcirculation of the nail bed.

Indocyanine green-enhanced fluorescence optical imaging in patients with early and very early arthritis: a comparative study with magnetic resonance imaging.

OBJECTIVE: Indocyanine green-enhanced fluorescence optical imaging (FOI) is a novel diagnostic tool for the assessment of inflammation in arthritis. We undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32 patients with early and very early untreated arthritis (mean disease duration 7.1 months). METHODS: FOI images were acquired with the commercially available Xiralite system. Image interpretation was done for an early phase (phase 1), an intermediate phase (phase 2), and a late phase (phase 3), and for an electronically generated composite image. The results were compared with those of clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI in a control group of 46 subjects without any signs of inflammatory joint disease (1,380 joints). RESULTS: With MRI as the reference method, the sensitivity of FOI was 86% and the specificity was 63%, while the composite image, phase 1, and phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results differed considerably between the composite image and the phases. FOI did not detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI. Intrareader and interreader agreements were moderate to substantial (κ = 0.55-0.73). In the control group, FOI showed positive findings in 5% of normal joints in phase 2. CONCLUSION: Further multicenter studies will address the question of whether FOI allows sensitive and reliable detection of inflammatory changes in early arthritis, as suggested by our initial findings. If this is confirmed, FOI has the potential to be a sensitive and valuable tool for monitoring disease activity on site in clinical settings and for serving as an outcome parameter in clinical trials.

Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology.

BACKGROUND: Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models. In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis. METHODS: 252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands. RESULTS: In an FOI sequence, three phases could be distinguished (P1-P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls. CONCLUSION: ICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.

Fluorescence optical imaging and musculoskeletal ultrasonography in juvenile idiopathic polyarticular disease before and during antirheumatic treatment - a multicenter non-interventional diagnostic evaluation.

BACKGROUND: Valid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring. METHODS: A 24-week observational study in polyarticular JIA patients newly starting treatment with methotrexate or an approved biologic was performed in three centers. Patients were evaluated clinically, by gray-scale ultrasonography (GSUS), power-Doppler ultrasonography (PDUS) and FOI at baseline, week 12 and week 24. RESULTS: Of 37 patients enrolled, 24 patients started methotrexate and 13 patients a biologic for the first time (etanercept n = 11, adalimumab and tocilizumab n = 1 each). Mean JADAS 10 decreased significantly from 17.7 at baseline to 12.2 and 7.2 at week 12 and 24 respectively. PedACR 30/50/70/100 response rates at week 24 were 85%/73%/50%/27%. The total number of clinically active joints in hand and fingers at baseline/week 12/week 24 was 262 (23.6%)/162 (16.4%)/162 (9.0%). By GSUS, at baseline/week 12/week 24, 192 (19.4%)/135 (16.1%)/83 (11.5%) joints showed effusions and 186 (18.8%)/107 (12.7%)/69 (9.6%) showed synovial thickening, and by PDUS 68 (6.9%)/15 (1.8%)/36 (5%) joints showed hyperperfusion. Any sign of arthritis was detected by US in a total of 243 joints (24.5%) at baseline, 161 joints (19.2%) at week 12 and 123 joints (17%) at week 24. By FOI at baseline/week 12/week 24, 430 (38.7%)/280 (29.2%)/215 (27.6%) showed a signal enhancement in at least one phase. Summarizing all three points of time, the highest numbers of signals were detected by FOI with 32% of joints, especially in phase 2, while by US 20.7% and by clinical examination 17.5% of joints were active. A high number of joints (21.1%) had FOI signals but were inactive by clinical examination. A total 20.1% of joints with signals in FOI did not show effusion, synovial thickening or hyperperfusion by US. Because of the high number of negative results, specificity of FOI compared with clinical examination/US/PD was high (84-95%), and sensitivity was only moderate. CONCLUSION: FOI and US could detect clinical but also subclinical inflammation. FOI detected subclinical inflammation to a higher extent than US. Improvement upon treatment with either methotrexate or a biologic can be visualized by FOI and US. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00011579 . Registered 10 January 2017.

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis.

BACKGROUND: The aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity. METHOD: We incubated 5892 recombinant proteins coupled to fluorescent beads, with patients' sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought. RESULT: Screening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2). CONCLUSIONS: Comprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

[Quality assurance of rheumatologic patient education]. / Qualitätssicherung bei der rheumatologischen Patientenschulung.

Since 1989 patient education programmes for patients with rheumatoid arthritis, ankylosing spondylitis and other spondylarthropathies, systemic lupus erythematosus, vasculitis, fibromyalgia, and juvenile chronic arthritis and their parents have been developed by an interdisciplinary team of the German Society of Rheumatology (Deutsche Gesellschaft für Rheumatologie). Up to date, about 500 people were trained to be group leaders or specialised trainers with an associated train-the-trainer program. In 1999, the Society discharged preliminary guidelines for patient education in rheumatology. Prospective randomised studies demonstrated that patient education led both to an improvement of knowledge, self-efficacy and self-help activities and to an improvement of arthritis-related helplessness and pain, and a reduction of both temporary and permanent disability.

[Biologics in the early treatment of ankylosing spondylitis and related forms of spondyloarthritis]. / Biologicals in der frühen Behandlung des M. Bechterew und verwandter Spondyloarthritiden.

New pathogenetic insights have identified the key role of TNF-alpha in inflammatory rheumatic diseases and have revolutionized the therapy of spondyloarthritides. TNF-alpha-antagonists specifically inhibit the pro-inflammatory effects of TNF-alpha. Clinical studies with infliximab (Remicade), Etanercept (Enbrel) or Adalimumab (Humira) in ankylosing spondylitis or related diseases demonstrate superior efficacy to conventional drugs like non-steroidal antirheumatic drugs or traditional disease modifying antirheumatic drugs.