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Objective Interleukin-6 (IL-6) is a pivotal cytokine in the pathogenesis of polymyalgia rheumatica (PMR), yet the efficacy of IL-6 blockade with tocilizumab (TCZ) for the treatment of PMR is unknown. The aim of this study was to assess the efficacy and safety of TCZ in newly diagnosed PMR. Methods. In a single-center open-label study, patients with newly diagnosed PMR who had been treated with glucocorticoids (GCs) for

Objective.To determine the inter/intraobserver reliability of the tender and swollen joint counts (TJC, SJC) and the modified Rodnan Skin Score (mRSS) in diffuse cutaneous systemic sclerosis (dcSSc) and to assess content validity of the TJC/SJC.Methods.Ten rheumatologists completed the SJC, TJC, and mRSS on 7 patients. Musculoskeletal ultrasound (MSUS) was performed.Results.Interobserver and intraobserver reliability for the TJC was 0.97 and 0.99, for the SJC was 0.24 and 0.71, and for the mRSS was 0.81 and 0.94, respectively. MSUS abnormalities did not correspond with SJC/TJC.Conclusion.We demonstrate excellent inter- and intraobserver reliability for the mRSS and TJC in dcSSc. However, the SJC and TJC did not correspond to MSUS.

This study evaluates a novel, three-part nailfold capillaroscopy training curriculum for adult and paediatric rheumatology fellows.All rheumatology fellows training at an academic medical centre took part in the three-part nailfold capillaroscopy curriculum. Tests of fellows' usage, interest, confidence, and ability in nailfold capillaroscopy were taken at multiple time-points throughout the curriculum.Fellows self-reported high levels of interest, increased confidence in delineating normal and abnormal nailfold capillaries (p=0.03) and increased usage of nailfold capillaroscopy (p=0.09). The ability of fellows to identify normal nailfold capillaries (p=0.03) and systemic sclerosis-specific nailfold capillary changes, such as neoangiogenesis (p0.001), also increased.The curriculum was feasible and led to improved ability of learners to distinguish normal from abnormal and to recognise and describe systemic sclerosis-specific nailfold capillary changes. This curriculum also led to improved confidence in examining nailfold capillaries and increased usage of this skill in rheumatologic consultation.

Interleukin-6 (IL-6) is a pivotal cytokine in the pathogenesis of polymyalgia rheumatica (PMR), yet the efficacy of IL-6 blockade with tocilizumab (TCZ) for the treatment of PMR is unknown. The aim of this study was to assess the efficacy and safety of TCZ in newly diagnosed PMR.In a single-center open-label study, patients with newly diagnosed PMR who had been treated with glucocorticoids (GCs) for1 month were treated monthly with intravenous (IV) TCZ 8 mg/kg for 1 year, with a rapid tapering of GCs according to standardized protocol. The primary end point was the proportion of patients in relapse-free remission without GC treatment at 6 months. Secondary outcome measures included duration of GC use and cumulative GC dose. Patients were followed up for 15 months.Ten patients were enrolled in the study. One patient withdrew after 2 months, leaving 9 patients in whom the primary end point was assessed. The primary end point of relapse-free remission without GC treatment at 6 months was achieved by all 9 of these patients. All patients who received TCZ treatment were able to discontinue GCs within 4 months of study entry. The cumulative mean ± SD prednisone dose was 1,085 ± 301 mg and the total duration of GC exposure was 3.9 ± 0.9 months. Remission persisted without relapse, in all 9 patients, throughout the entire 15-month study.Our findings suggest that TCZ may be an effective, safe, and well-tolerated treatment for newly diagnosed patients with PMR, with a robust steroid-sparing effect.

The transcription factor cAMP responsive element binding protein (CREB) is important in regulating immediate-early genes and some late-effector genes involved in neuroplasticity in response to peripheral injury and stressful insults. Partial nerve injury elicited neuropathic pain is accompanied by increased phosphorylation of CREB in the ipsilateral spinal cord dorsal horn (Ma and Quirion, Pain 93 (2001) 295; Miletic et al., Pain 99 (2002) 493). The aim of this study is to determine whether increased phosphorylation of CREB in the dorsal horn contributes to the pathogenesis of neuropathic pain. Three weeks following partial sciatic nerve ligation (PSNL), daily intrathecal injection of antisense CREB oligodeoxynucleotide (ODN, 20 μg/day) for 5 days significantly attenuated tactile allodynia. The attenuation lasted for more than 4 days. Total CREB and phosphorylated CREB in both ipsilateral and contralateral dorsal horn neurons were dramatically reduced in antisense ODN injected PSNL rats 1 week after injection. The extent of reduction of total CREB and phosphorylated CREB containing cells in the dorsal horn ipsilateral to injury was greater than in the contralateral dorsal horn. These data suggest that phosphorylation of CREB is an important contributing event in the central plasticity of nerve injury and in the pathogenesis of neuropathic pain.