Bone Turnover Markers and Wnt Signaling Modulators in Early Complex Regional Pain Syndrome. A Pre-specified Observational Study.

To explore serum levels of some bone turnover markers and the involvement of the Wnt signaling in CRPS-1. Query ID="Q1" Text="Please check and confirm whether the edit made to the article title is in order." We conducted an observational study on patients with early CRPS-1 recruited before any treatment. Clinical measures were assessed together with biochemical evaluation. Values of sclerostin, DKK1, CTX-I, and P1NP were compared with sex-age-matched healthy controls (HCs). We enrolled 34 patients diagnosed with CRPS-1 (mean age 59.3 ± 10.6 years, Male/Female 10/24), median disease duration = 2 weeks (IQR 1-5); median VAS score = 76 (IQR 68-80). Foot localization was slightly more frequent than hand localization (18/16). No statistically significant difference was found between CRPS-1 patients and HCs for CTX-I (0.3 ± 0.1 ng/ml vs 0.3 ± 0.1, p = 0.140), while mean serum values of P1NP were significantly higher in CRPS-1 patients compared to HCs (70.0 ± 38.8 ng/ml vs 50.1 ± 13.6, p = 0.005). Mean levels of sclerostin and DKK1 were lower in CRPS-1 patients vs HCs (sclerostin 28.4 ± 10.8 pmol/l vs 34.1 ± 11.6, p = 0.004; DKK1 12.9 ± 10.8 pmol/l vs 24.1 ± 11.9, p = 0.001). No statistically significant difference was found for all biochemical assessments in a subgroup of fracture-induced CRPS-1. No statistically significant differences were observed according to disease localization, disease duration, presence of hyperalgesia, allodynia, sudomotor alterations, and mild or moderate/severe swelling. No significant correlation emerged between sclerostin, DKK1 levels, baseline VAS score, or McGill Pain Questionnaire score. Bone involvement in early CRPS-1 does not seem to rely on increased osteoclast activity. Conversely, a serum marker of bone formation resulted increased. Both Sclerostin and DKK1 showed decreased values, probably suggesting a widespread osteocyte loss of function.Trial registration number: Eudract Number: 2014-001156-28.

COVID-19 related poor mental health and sleep disorders in rheumatic patients: a citizen science project.

BACKGROUND: Patients with chronic rheumatic diseases (RDs) are more vulnerable and the containment measures related to the COVID-19 pandemic might have severe psychological consequences. We investigated the presence of and risk factors associated with poor mental health, sleep disorders among RDs during the pandemic. METHODS: This cross-sectional Italian citizen science project evaluated the psychological impact of the COVID-19 pandemic in patients with RDs. Between May and September 2020, eleven RD patients' associations sent the survey by using their mailing list and the related webpage and social network. 507 RD patients completed an ad-hoc anonymous online survey including the Perceived Stress Scale (PSS) and Impact Event Scale-Revised (IES-R). RESULTS: The mean scores on the PSS-10 and the IES-R were 18.1 and 29.7, respectively. Higher PSS scores were associated with younger age (p <  0.01), female gender (p <  0.01), overweight/obesity (p = 0.01), psychiatric pharmacotherapy (p <  0.01), and anxiety for loss of income (p <  0.01). Higher IES-R scores were associated with female gender (p <  0.01), intestinal diseases (p = 0.03), anxiety (p <  0.01), and health concern (p <  0.01). Among 375 patients with inflammatory arthritis, 246 (65.6%) had trouble staying asleep, 238 (63.5%) falling asleep, and 112 (29.9%) had dreams about the pandemic. Older age (OR = 1.038, CI 1.002-1.076), psychiatric pharmacotherapy (OR = 25.819, CI 11.465-58.143), and COVID infection (OR = 2.783, CI 1.215-6.372) were predictive of insomnia during the pandemic. CONCLUSIONS: A considerable COVID-19 related psychosocial burden has been detected in RDs. Different factors were predictive of poor mental health and sleep disorders in these patients. Focused supportive strategies should be implemented to improve the psychological well-being of fragile patients during pandemics.

Effect of neridronate on axial involvement in patients with spondyloarthritis when biologics are not possible. Results of a monocentric study.

Introduction: This study aims to examine the potential effectiveness of intravenous neridronate (IVNer) on axial involvement in patients with spondyloarthritis (SpA) refractory to non-steroidal anti-inflammatory drugs (NSAIDs) but not eligible for biological disease-modifying antirheumatic drugs (bDMARDs). Method: Patients with active SpA (BASDAI score ≥ 4) and active sacroiliitis (SI) on MRI (according to ASAS MRI definition), who were NSAID-insufficient responder/intolerant but not eligible for bDMARDs, were retrospectively recruited in a tertiary rheumatology centre between September 2015 and December 2021. IVNer (100 mg) was administered to the patients on days 1, 4, 7, and 10. Responses were evaluated 60 days after the last infusion as the median changes from the baseline of BASDAI and Visual Analogue Scale (VAS) pain and there are improvements on MRI signs. Results: A total of 38 patients (26 axial SpA, 3 enteropathic arthritis, and 9 axial psoriatic arthritis) were included [66% women, mean age ± SD: 38.0 ± 14.1 years, mean disease duration: 30.5 ± 49.5 months (range 1.0-298), 47% HLAB27+]. The reason for bDMARD ineligibility was concurrent solid tumors (n = 6) or hematological (n = 1) malignancy, comorbidities (n = 11), or patient preference (n = 20). Both median BASDAI [5.83 (4.2-8.33) versus 3.66 (1.1-6.85), p < 0.001] and VAS pain [7 (5.75-8.0) versus 3 (1.0-7.0), p < 0.0001] significantly decreased after IVNer. Of 28 available MRI at follow-up, we observed a complete (36%) or partial (39%) resolution of sacroiliitis or a persistent activity (25%). Discussion: IVNer was effective in improving axial involvement in patients with SpA refractory to NSAIDs but not eligible for bDMARDs. IVNer can be considered as a potential alternative therapeutic option in selected settings.

Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review.

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

The impact of EMA recommendations on the real-life use of Janus kinases inhibitors for rheumatoid arthritis: the Expanded Risk Score in RA as a tool to quantify the risk of cardiovascular events.

Objective: To evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE). Methods: We conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA. Results: Of 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p<0.001 versus ORALSURV), leading to 46.4% overall ineligible patients. Over a drug-exposure of 337 patient/years, we observed 2 VTE, one MACE (non-fatal stroke), and one solid malignancy (all in the group of patients classified as ineligible according to both the definitions). Conclusions: Rigorous application of EMA indications in clinical practice could result in the exclusion of a large proportion of RA patients from treatment with JAKis. A proper quantification of the risk for MACE by dedicated tools as ERS-RA is advocated to better tailor the management of RA.

A case report of monoarthritis in a COVID-19 patient and literature review: Simple actions for complex times.

RATIONALE: COVID-19 presentation is multifaceted and up to 44% of patients affected by COVID-19 experience musculoskeletal complaints, mostly in the form of diffuse aspecific arthromyalgias. Nevertheless, only a few cases of arthritis following SARS-CoV2 infection are reported. PATIENT CONCERNS: A 27-year-old man affected by nail psoriasis presented with monoarthritis 2 weeks after being diagnosed with COVID-19. DIAGNOSES: Diagnostic work-up and differential diagnosis were made difficult by patient isolation, absence of lab tests, and his visit via telemedicine, even though signs of first metacarpophalangeal joint involvement were clear. INTERVENTIONS: Due to the inefficacy of acetaminophen and nonsteroidal anti-inflammatory drugs, the patient was prescribed oral steroids with a rapid benefit. OUTCOMES: The patient's response to oral steroid was prompt and maintained even after therapy tapering. Even so, a formal diagnosis was not possible due to a difficult diagnostic work-up and lack of a long-term follow-up. LESSONS: Like many other viral diseases, SARS-CoV2 can play as a causative agent or as a trigger for inflammatory arthritis development in predisposed individuals.