Raynaud's Phenomenon Research Articles

The role of nailfold video-capillaroscopy in the assessment of dermatomyositis.

The clinical manifestations of dermatomyositis (DM) are diverse, nailfold video-capillaroscopy (NVC) can reflect microangiopathy, a process believed to contribute significantly to the clinical manifestations of DM. We aimed to explore the distinctive alterations and implications of nailfold capillary for evaluating disease progression in individuals with DM. We gathered clinical data from 76 DM patients who underwent NVC in the Affiliated Hospital of Nantong University between September 2017 and September 2022. Additionally, we recruited 26 anti-synthase antibody syndrome (ASS) patients and 33 systemic sclerosis (SSc) patients as controls. Utilizing an unsupervised machine learning method (hierarchical clustering analysis) to categorized patients based on NVC results and compared clinical characteristics and survival outcomes. The follow-up period ended in December 2022. Anomalous NVC patterns were detected in 73.7% of the 76 DM patients and manifested as diminished capillary density and abnormal capillary morphology. Patients displaying abnormal NVC findings exhibited a significantly higher prevalence of Raynaud's phenomenon and a greater likelihood of being managed with triple combination therapy. Compared with SSc patients, milder NVC changes were observed in patients with DM; nonetheless, NVC abnormalities were more prominent in DM patients when contrasted with individuals with ASS. Furthermore, the patients were classified into two different clusters according to NVC data. Patients in cluster 1 were more likely to develop interstitial lung disease (ILD). Survival outcomes did not differ significantly between the two clusters. DM patients can experience varying degrees of aberrant NVC patterns, which can impact ILD risk and warrant clinical vigilance.

Barnidipine as a potential alternative treatment for Raynaud's phenomenon secondary to systemic sclerosis: a retrospective pilot study.

To assess short-term barnidipine efficacy and tolerability on Systemic Sclerosis (SSc)-Raynaud's phenomenon (RP). We retrospectively evaluated patients with SSc starting barnidipine 10mg/day. Raynaud's Condition Score (RCS) and mean blood pressure (MBP) were assessed at baseline and 6-month follow-up. Discontinuation rates and adverse events (AEs) were compared with retrospectively evaluated patients who started MR-nifedipine 20mg/day at our centre. Sixty-four patients (29 barnidipine, 35 MR-nifedipine) were evaluated. Most patients starting barnidipine had a previous CCB exposure (69%; 57.9% of these were withdrawn for AEs). During follow-up, RCS decreased significantly (6.6 ± 1.8 vs 4.4 ± 1.8, p < 0.001), while the MBP did not change significantly (86.4 ± 8.4 vs 85 ± 7.3mmHg; p = 0.36). Nine patients (31%) discontinued barnidipine during the follow-up (AEs 6/9, inefficacy 3/9). Previous CCB failure did not predict barnidipine withdrawal (OR = 0.188 95%CI [0.02-1.8]; p = 0.147). No predictors of barnidipine withdrawal were found, and no clinical or demographic differences were found between patients withdrawing and continuing barnidipine. The 6-month retention rates of barnidipine and MR-nifedipine did not differ significantly (69 vs 80%; log-rank p = 0.23), and the two groups had a similar incidence of AEs leading to discontinuation (20.1 vs 17%; p = 0.48). Barnidipine could be an effective and well-tolerated therapeutic option to treat SSc-RP, even in patients previously failing other CCBs. Key Points •Calcium channel blockers (CCBs) currently represent the first-line treatment forRaynaud's phenomenon secondary to Systemic Sclerosis (SSc-RP). However, littledata exists about using novel CCBs, such as barnidipine, in this condition. •This study retrospectively evaluated patients with SSc-RP treated with barnidipine toassess its short-term efficacy. To serve as a control group for tolerability, weretrospectively compared these patients with others starting modified release-nifedipine (MR-nifedipine). •In patients treated with barnidipine, we observed a significant decrease in Raynaud's condition score at the 6-month follow-up without substantial changes in mean blood pressure. •The proportion of adverse events and drug withdrawal rate between patients starting barnidipine and MR-nifedipine did not differ significantly, even in patients starting barnidipine after previously failing other CCBs.

Surgical and oncological outcomes of salvage radical prostatectomy after focal therapies: a matched-pair analysis.

To determine the surgical and oncologic outcomes of salvage radical prostatectomy (sRP) after FT failure. Patients who consecutively underwent primary RP or sRP after FT failure between 2008 and 2022 were retrospectively selected. Primary or sRP were performed with either a robot-assisted or open approach. All surgeries were performed by surgeons with experience of ≥ 500 cases. Biochemical recurrence-free survival (BFS), intra- and postoperative surgical and functional outcomes were assessed. To evaluate the impact of surgical setting, propensity score (PS) matching was performed. 80 patients received sRP. Outcomes were analyzed using PS-matched cohorts (203 RPs vs. 68 sRPs). After a median follow-up of 25.4 months, sRP and RP had equal BFS (24mo-BFS: 72.4% vs. 76.0% (p = 0.8)). No statistically significant differences were found between sRP and RP in terms of median operative time (OT) (171min vs. 168min), estimated blood loss (EBL) (500ml vs. 500ml), length of hospital stay (LOS) (7 days vs. 7 days) and time to catheter removal (11 days vs. 11 days) and 1-year continence rates (all standardized mean differences ≤ 0.1). The main limitation is the retrospective study design. In the hands of experienced surgeons, sRP after FT offered comparable surgical and oncologic outcomes as RP in a primary setting.

Wearable in Systemic Sclerosis: A Pilot Study of the Apollo Wearable Demonstrates Improvement in Fatigue, Raynaud Phenomenon and Quality-of-Life in Patients with Systemic Sclerosis.

In systemic sclerosis (SSc) patients, fatigue is the highest ranked symptom affecting quality of life (QoL), followed by Raynaud phenomenon (RP). We report results from a pilot study (NCT04854850) of the Apollo wearable device in SSc patients. Twenty-five adult participants with SSc, moderate fatigue and RP were enrolled. Participants completed a 4-week intervention, during which they wore the Apollo device daily for a minimum of 15 minutes. The primary outcome was change on the PROMIS-Fatigue 13a (PROMIS-Fatigue) scale at 4 weeks. (ClinicalTrials.gov Identifier: NCT04854850) RESULTS: After 4 weeks of using the Apollo wearable, participants reported less fatigue on the PROMIS-Fatigue (p <0.001) scale. The average daily number of RP attacks declined (p < 0.01), as did the Raynaud condition score (p<0.001) after 4 weeks of use. Average device usage (2.87 hours per day) far exceeded the requested time, and no adverse events occurred. The PROMIS-29 sub scores assessment demonstrated quality of life (QoL) improvement in physical function (p <0.01), sleep disturbance (p = 0.001), and ability to participate in social roles and activities (p < 0.001). Significant improvements were also noted for depression (p < 0.01) and disability (p < 0.05) measures. Use of the Apollo wearable for four weeks was associated with improvement in fatigue and RP symptom in SSc patients, with improved QoL measures and lower depression scores. Future studies should further test the efficacy of the Apollo wearable in these domains and SSc patient QoL.

An overview on pharmaceutical applications of phosphodiesterase enzyme 5 (PDE5) inhibitors.

Phosphodiesterase enzyme 5 (PDE5) inhibitors have emerged as one of the leading molecules for the treatment of erectile dysfunction (ED). PDE5 inhibitors are categorized structurally into several classes. PDE5 inhibitors have been a multidisciplinary endeavor that attracts the attention of researchers because of their multiple pharmaceutical applications. Beyond their action on ED, PDE5 inhibitors are widely used in treatment of benign prostatic hypertrophy (BPH), Eisenmenger's syndrome, Raynaud's Disease, Intrauterine growth retardation (IUGR), Mountain sickness, Bladder pain syndrome/interstitial cystitis (BPS/IC), pulmonary arterial hypertension and type II diabetes (insulin resistance). In addition, PDE5 inhibitors also show promising antiproliferative activity, anti-Alzheimer and COX-1/COX-2 inhibitory activity (anti-inflammatory). Pharmacokinetics, Pharmacogenetics and toxicity of PDE5 inhibitors were finally explored. The diverse therapeutic applications, the high feasibility of structural modification and the appropriate pharmacokinetic properties of PDE5 inhibitors have motivated researchers to develop new scaffolds that have been either under clinical trials or approved by FDA and utilize them to overcome some recent global concerns, such as COVID-19.

Relationships Among Capillary Refill Time, Peripheral Blood Flow Rate, and Fingertip Temperature: Advances in Peripheral Artery Contractility Diagnosis.

Capillary refill time (CRT) is a widely used noninvasive measure of cardiovascular health. Despite its widespread diagnostic utility, it has several limitations, particularly its low sensitivity for certain conditions, because factors such as the contraction and relaxation of distal blood vessels can influence CRT readings. This study was performed to explore the relationships between CRT and distal blood flow. The right hand of each of 10 healthy adult volunteers was cooled to induce blood vessel contraction. CRT, fingertip temperature, and blood flow rate were measured using a custom device, a thermometer, and a laser Doppler blood flow meter, respectively, before and after cooling. Hand cooling significantly decreased blood flow rate and increased CRT. A robust inverse correlation was observed between blood flow rate and CRT, supporting a model where CRT is the time required for blood to flow through a cylindrical pipe. Furthermore, CRT showed a significant negative correlation with fingertip temperature. Most participants had high correlation coefficients, although two showed lower values. However, all data points exhibited a linear relationship, with the slopes of the regression lines between CRT and temperature varying among participants. These results suggested that the slope between CRT and fingertip temperature indicates individual differences in arterial contractility. These findings could improve the diagnostic utility of CRT in assessing vascular health, including arterial age and Raynaud's phenomenon, based on the contractility of peripheral arteries.

Clinico-sero-pathological characteristics of anti-Ha antisynthetase syndrome.

To define the clinical, serological, and muscle histopathological characteristics, as well as treatment outcomes, of patients with anti-Ha antibody. We performed a retrospective analysis of clinical, serological, and pathological data and long-term treatment outcomes of anti-Ha patients between January 2005 and July 2023 at our center. Anti-Ha antibody was identified by immunoblot and reconfirmed by immunoprecipitation. Of the 570 patients with idiopathic inflammatory myopathies, 17 (3.0%) were found to be anti-Ha positive, of whom 5 (29.4%) were also positive for another myositis-specific antibody (MSA). All patients with anti-Ha antibody as the single MSA (12/17, 70.6%) had clinical and histopathological evidence of muscle damage. Skin lesions were identified in nine of them (75%), while both interstitial lung disease and Raynaud's phenomenon were only seen in four patients. A necrotizing myopathy without a perifascicular pattern was the most common pathological manifestation (50%). Perifascicular necrosis (PFN) and myofiber major histocompatibility complex class-II expression were observed only in one and four patients, respectively. Muscle weakness relapse was reported in five patients, and skin rashes worsening were observed in one patient. Most of the anti-Ha patients (66.7%) finally achieved a favorable outcome at last follow-up. Anti-Ha antibody might not be as rare as previously thought and may coexist with other MSAs. Muscle damage is the most common manifestation in anti-Ha patients, while extra-muscular symptoms except for the cutaneous manifestations are unusual. The histopathological features varied with a predominance of necrotizing myopathy without PFN. These patients often finally had favorable outcomes, although relapses often occur.

Impact of Season, Environmental Temperature, and Humidity on Raynaud Phenomenon in an Australian Systemic Sclerosis Cohort.

The aim of this study was to determine the impact of season, temperature and humidity on the severity of Raynaud phenomenon (RP) in systemic sclerosis. Data from the Australian Scleroderma Cohort Study were used to assess associations of patient-reported worsened RP in the month preceding each study visit. Mean monthly weather data were obtained from the closest weather station to the patient's address. We evaluated the relationship between worsened RP and health-related quality of life (HRQoL) measured using the Short Form 36 instrument. Among 1,972 patients with systemic sclerosis, RP was a near-universal finding, and worsened RP in the preceding month was reported in 26.7% of 9,175 visits. "Worsened RP" showed significant environmental variability. On multivariable analysis, worsened RP was associated with low mean maximum temperatures (odds ratio [OR] 0.91, 95% confidence interval [95% CI] 0.90-0.92, P < 0.001), high relative humidity (OR 1.05, 95% CI 1.04-1.05, P < 0.001) and lower mean daily evaporation (OR 0.77, 95% CI 0.73-0.81, P < 0.001). Worsened RP was strongly associated with telangiectasia, calcinosis, and digital ulceration, as well as demonstrating an association with anticentromere antibody and gastroesophageal reflux disease and a negative correlation with diffuse disease. Worsened RP was also strongly associated with worse HRQoL. Lower environmental temperature and higher relative humidity had significant associations with worsened RP in this systemic sclerosis cohort, suggesting an important role for dry warmth in managing this condition.

A Phase II study of avenciguat, a novel soluble guanylate cyclase activator, in patients with systemic sclerosis: Study design and rationale of the VITALISScE™ study.

Systemic sclerosis is a rare autoimmune connective tissue disease characterised by (1) microvasculopathy; (2) immune dysregulation; and (3) progressive fibrosis of the skin and internal organs. Soluble guanylate cyclase plays an important role in maintaining vascular and immunological homeostasis and preventing organ fibrosis. Pharmacological modulation of soluble guanylate cyclase with soluble guanylate cyclase stimulators has shown anti-inflammatory and antifibrotic effects in animal models of systemic sclerosis, with a trend towards clinical efficacy in a Phase II study (RISE-SSc). However, the efficacy of soluble guanylate cyclase stimulators may be reduced under conditions of hypoxia and oxidative stress. Soluble guanylate cyclase activators have the potential to overcome this limitation. This paper describes the study design of VITALISScE™, a Phase II clinical trial assessing the efficacy, safety and tolerability of avenciguat, a novel soluble guanylate cyclase activator in patients with active systemic sclerosis at risk of progression. The VITALISScE™ study (NCT05559580) is evaluating the action of avenciguat on all three aspects of systemic sclerosis pathophysiology. The primary endpoint is the rate of decline in forced vital capacity (mL) over 48 weeks. Secondary endpoints include absolute change from baseline at Week 48 in modified Rodnan skin score, Health Assessment Questionnaire Disability Index score and the proportion of responders based on the revised Composite Response Index in Systemic Sclerosis. Additional endpoints include a composite assessment of Raynaud's phenomenon, digital ulcer burden, functional outcomes and quality of life, safety, pharmacokinetics, and biomarkers associated with systemic sclerosis and the mechanism of action of avenciguat. VITALISScE™ is an ongoing, multicentre (180 sites; 38 countries), placebo-controlled, double-blind, parallel-group, Phase II clinical study. Recruitment is currently ongoing. The VITALISScE™ study is assessing the efficacy, safety and tolerability of avenciguat in patients with active systemic sclerosis at risk of progression. Results will inform further development of avenciguat. VITALISScE™; EU CT No. 2022-500332-11-00; Clinicaltrials.gov: NCT05559580 (https://www.clinicaltrials.gov/study/NCT05559580).

The B-cells paradigm in Systemic Sclerosis: an update on pathophysiology and B-cell targeted therapies.

Systemic sclerosis is considered a rare autoimmune disease in which there are alterations of both the innate and adaptive immune response resulting in the production of autoantibodies. Abnormalities of the immune system compromise the normal function of blood vessels leading to a vasculopathy manifested by Raynaud's phenomenon, an early sign of systemic sclerosis. As a consequence of this reactive picture, the disease can evolve leading to tissue fibrosis. Several systemic sclerosis-specific autoantibodies are currently known and are associated with specific clinical manifestations and prognosis. Although the pathogenetic role of these autoantibodies is still unclear, their production by B cells and plasma cells suggests the importance of these cells in the development of systemic sclerosis. This review narratively examines B cell dysfunctions and their role in the pathogenesis of systemic sclerosis and discusses B cell-targeted therapies currently used or potentially useful for the management of end-organ complications.

Sjögren's syndrome positive for isolated anti-Ro52/SS-A antibody and anti-centromere antibody.

This current case report describes a Japanese woman in her 80s with xerostomia who presented with salivary gland dysfunction. She was positive for isolated anti-Ro52/SS-A antibody as determined by a chemiluminescent enzyme immunoassay and positive on a fluorescence enzyme immunoassay that recognizes both Ro52 and Ro60 antigens. A high serum concentration of anti-Ro52/SS-A antibody was determined by an enzyme-linked immunosorbent assay. A high anti-centromere antibodies (ACA) titre was also observed. Although Raynaud's phenomenon or a high serum immunoglobulin G concentration were not observed, Masson-trichrome staining of the patient's labial salivary glands showed considerable fibrosis. Her serum type I and type II interferon concentrations were normal. The present patient is the first with Sjögren's syndrome (SS) to exhibit isolated anti-Ro52/SS-A antibody and ACA without anti-Ro60/SS-A antibody. This current case report presents her case together with those of four other SS patients who were positive for isolated anti-Ro52/SS-A antibody. The SS literature also includes cases positive for ACA and describes clinical characteristics. The other four SS patients with isolated anti-Ro52/SS-A antibody described here had no ACA; interstitial pneumonia and polyneuropathy were observed in these cases, although there was no consistent tendency regarding types I and II interferon.

Botulinum Toxin for the Treatment of Raynaud's Conditions of the Hand: Clinical Practice Updates and Future Directions.

Raynaud's conditions of the hand, referred to commonly as Raynaud's phenomenon, both primary and secondary, represents a spectrum of disorders affecting the digits, characterised by recurrent episodes of vasospasm that result in a triad of symptoms: pain, pallor, and cyanosis. Various therapies, ranging from conservative hand therapy techniques to surgical sympathectomy, have been explored with inconsistent results. Recently, the local administration of botulinum toxin type-A (BTX-A) has re-emerged as a treatment option for this condition. This review delves into the mechanistic pathways of BTX-A therapy, optimal dosing concentrations, administration techniques, and its safety profile. A critical analysis of published studies to date demonstrates varied clinical efficacy of BTX-A in Raynaud's conditions based on patient-reported outcome measures and objective measures of outcomes assessment. Thus, in order to accurately assess the clinical effectiveness of BTX-A in future robust studies, this review emphasises the importance of streamlining patient selection to minimise heterogeneity in disease severity, optimising recruitment to ensure adequate statistical power, and establishing sensitive outcome measures to monitor response and discern treatment efficacy. Additionally, addressing concerns such as minimising antibody resistance, extending the duration of treatment effects on tissues, and exploring new modalities to assess hand perfusion will be focal points for future research and BTX-A drug development.

Primary headache in SLE –systematic review and meta-analysis

ObjectivesTo systematically review and synthesize literature on: 1) the overall prevalence of primary headaches and specifically migraines, in patients with lupus since previous systematic review published in 2004; 2) the risk factors associated with primary headaches in patients with lupus; 3) the association of primary headaches with structural brain changes; and 4) “lupus headaches”. MethodsThis review used (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guidelines and literature searches in four databases: Ovid-based Medline, Embase, PsycINFO, and Cochrane Database of Systematic Reviews from inception until 4/2022. Papers on primary headaches in patients with lupus were identified. Included studies were critically appraised and analyzed. Since a systematic review on this topic was published in 2004, only papers published in 2004 and later were included in this review. Statistical and publication bias was assessed using funnel plots. ResultsA total of 5096 references were identified, 189 were selected for detailed review and 11 papers were included in the final analysis. 1) The pooled prevalence of primary headaches in lupus was 26.8 % (95 %CI 25.1–28.6). The prevalence of primary headaches was similar between patients with lupus and healthy controls, odds ratio (OR) 2.14, 95 %CI 0.97–4.76, p value=0.06, however publication bias was significant according to the Egger test. Lupus patients seem to have a higher prevalence of primary headaches compared to patients with rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS), OR 2.5, 95 % CI 1.56–4, p < 0.0001. Regarding the prevalence of migraines specifically, no difference was found between patients with lupus compared to healthy controls and patients with RA or pSS. 2) Primary headaches seem to be associated with depression and impaired health related quality of life rather than lupus activity or damage. There is insufficient data to conclude whether specific lupus treatments affected primary headaches in lupus, however, one study did suggest hydroxychloroquine reduced the frequency of primary headaches. Raynaud phenomenon was associated with migraines. 3) One study which examined MRI scans of patients with lupus compared to healthy controls did suggest that larger gray matter volumes reduced the odds for headaches in general (OR 0.98, p = 0.048) and for migraines in particular (OR 0.95, p = 0.004), and larger white matter volumes increased the odds for migraine (OR 1.04, p = 0.007). However, these findings might reflect disease activity or damage, therefore further studies are required to clarify this issue. 4) The only study which specifically addressed the prevalence of “lupus headaches” is Hanly's study from 2013 of the SLICC cohort. In this large cohort, only 1.5 % of patients had "lupus headaches", as defined by SLE Disease Activity Index-2000 (SLEDAI-2 K). Therefore “Lupus headache” is a rare entity in SLE and should be suspected after excluding other possible explanations for headaches, especially when there is no known prior history of primary headaches. ConclusionsPatients with lupus seem to have a similar prevalence of primary headaches, and specifically migraines, compared to healthy controls. These primary headaches are associated with depression and Raynaud phenomenon and not with disease activity nor damage. Scarce data is published regarding structural changes associated with primary headaches. Currently is seems “lupus headaches” are a distinct rare manifestation of lupus and more data are needed.

Patients with systemic sclerosis frequently use phytopharmaceuticals: a cross-sectional survey.

The use of complementary and alternative medicine (CAM) has increased. Phytotherapy, also known as herbal medicine, is one of the CAM therapies that involves using medicinal plants and plant-derived substances. This study aims to evaluate the use of phytopharmaceuticals and the factors associated with their use in patients with Systemic sclerosis (SSc). Our study is designed as a survey and consists of two parts with 32 questions. The first part gathers demographic data with 14 questions, and the second part assesses participants' knowledge about phytotherapy with 18 questions. The questionnaire was administered face-to-face to patients with SSc who consented to participate. One hundred participants completed the survey. Fifty-two (52%) participants had diffuse sclerosis. Raynaud's phenomenon affected 97 (97%) participants; 53 (53%) participants suffered from lung involvement, and 64 (64%) had musculoskeletal system involvement. A total of 55 (55%) participants had used phytopharmaceuticals after SSc diagnosis. Phytotherapy users and non-users had similar demographic and clinical characteristics in terms of age, gender, disease duration, type of SSc, organ involvement, and education level. Participants mostly used the following phytopharmaceuticals: 23 participants used Camellia sinensis (green tea), 16 used Hypericum perforatum, and 12 used Curcuma longa (curcumin). The most improved symptoms with phytopharmaceuticals were musculoskeletal system findings and skin thickness, as stated by participants. A significant portion of SSc patients used phytopharmaceuticals in their disease duration. Although patients stated that they benefited from phytopharmaceuticals, studies on the effectiveness of these treatments are insufficient.

Nailfold videocapillaroscopy abnormalities and vascular manifestations in Behçet's syndrome.

To evaluate microcirculation abnormalities and their clinical association in patients with BS, especially with vascular manifestations. A cross-sectional study was carried out using nailfold videocapillaroscopy (NVC) to evaluate the microcirculation in patients with BS. A total of 65 patients were included in the study. Thirty-four (52.3%) were men, and 84.6% were European Caucasian. Vascular involvement was present in 24 (36.9%) patients. Qualitative abnormalities in NVC were observed in 47.7% of patients. The most frequent were tortuous and branched capillaries (21.5%), followed by microhaemorrhage (12.3%), enlarged capillary (7.7%) and giant capillary (3.1%). We found a significant relationship between the presence of tortuous and branched capillaries and previous superficial thrombophlebitis (ST) (p=0.025). The presence of ≥2 qualitative abnormalities in NVC was associated with vascular involvement (p=0.031), mainly with venous thrombotic events (p=0.024) and particularly with ST (p=0.003). No specific Cutolo's pattern was observed. No association was observed between NVC and Raynaud's phenomenon or ANA, although patients with positive ANA presented more frequent non-specific capillaroscopic abnormalities (p=0.003). The presence of ≥2 qualitative abnormalities in NVC is associated with Vasculo-Behçet. NVC might be a potential tool for early detection of patients at risk of vascular events.

Development and validation of the RQLQ: a Raynaud’s disease–specific measure of health-related quality of life

Introduction/objectivesThe aim of this study was to develop and validate the Raynaud Specific Quality of Life Questionnaire (RQLQ) for assessing health-related quality (HRQOL) of life in patients with Raynaud’s disease (RD).MethodThe questionnaire was developed and validated in three stages. Initially, semi-structured interviews with 28 RD patients identified domains of everyday life affected by RD, leading to the creation of the initial RQLQ. In the first quantitative stage, 101 patients completed the RQLQ, and exploratory factor analysis assessed dimensionality and factor structure. After removing poorly performing items, the final RQLQ was tested with 102 patients. This stage also evaluated convergent, divergent, and discriminant validity, as well as internal reliability.ResultsFrom the interviews, 135 items were generated, with factor analysis refining the measure to 29 items across five subscales, showing good internal consistency. The RQLQ demonstrated significant correlations with self-rated quality of life and physical and mental health outcomes, confirming convergent and divergent validity. It also showed discriminant validity for different levels of disease activity.ConclusionsThe RQLQ is the first specific HRQOL measure for RD patients, proving to be a psychometrically sound, reliable, and valid tool for clinical research and practice.Key Points• The Raynaud Specific Quality of Life Questionnaire (RQLQ) is an important scale that evaluates the quality of life of patients with Raynaud’s disease.• The questionnaire showed good validity and reliability a capturing disease-specific quality of life.• This tool may aid in clinical research and practice.

Efficacy and safety of digital nerve block for pain management during sharp debridement of digital ulcers in systemic sclerosis: A prospective observational study.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vascular abnormalities, often leading to the development of digital ulcers (DUs). DUs are painful and debilitating, significantly impacting patients' quality of life. Effective pain management during debridement is crucial, yet there is no consensus on the optimal approach. This study evaluates the efficacy and safety of digital nerve block (DNB) using lidocaine and mepivacaine for pain control during sharp debridement of DUs in SSc patients. This prospective observational study was conducted from September 2023 to May 2024 at the Rheumatology Operating Unit, University of Verona. Patients were randomized to receive either 1 mL of 2% lidocaine or 2% mepivacaine for DNB. Pain levels were assessed using a categorical grading scale during the injection and debridement. The outcomes were pain control and performance of lidocaine versus mepivacaine. The cohort developed 46 ulcers. The pain was abolished in almost all patients. Lidocaine achieved faster anaesthesia (127.92 ± 34.32 s) compared with mepivacaine (252.65 ± 49.89 s, p < 0.001). Mepivacaine resulted in less pain during injection (p = 0.006). No significant difference in pain levels during debridement was observed between the two anaesthetics. Three mild adverse effects (Raynaud's phenomenon) were reported. All procedures were completed successfully, and 35 ulcers healed with a mean time of 6.1 ± 7.77 weeks. DNB with mepivacaine provides effective pain control during DU debridement in SSc patients, with lower injection site pain and comparable efficacy to lidocaine. The procedure is safe, well-tolerated and facilitates successful ulcer healing. Further studies with larger cohorts are warranted to confirm these findings.

8255 Munchausen Syndrome After Partial Pancreatectomy for Insulinoma: A Case Report

Abstract Disclosure: C.R. de Macedo: None. T.D. Bertolacini da Silva: None. I.P. de Magalhães: None. M.A. Pereira: None. I.C. Marques: None. J.L. Pinheiro Filho: None. G.F. Darce: None. D.M. Lourenço Junior: None. Background: Insulinoma is a rare, insulin-secreting pancreatic neuroendocrine tumor, most commonly benign, solitary, sporadic, well differentiated and with a slight female predominance. The investigation of hypoglycemia requires a fasting test to exclude, among other causes, factitious hypoglycemia. Clinical Case: A 27-year-old woman was admitted to the emergency room after seizure by hypoglycemic crisis (capillary blood glucose &amp;lt; 55 mg/dL). She had recurrent episodes of adrenergic/neuroglycopenic symptoms since the age of 14, occurring during fasting, mainly in the morning, with improvement after eating. After confirming Whipple's triad, a fasting test showed hyperinsulinemic hypoglycemia (glycemia 53 mg/dL, normal value &amp;gt;55 mg/dL; insulin 11.5 mcU/mL, nv &amp;lt;3mcU/mL) and increased C-peptide (3.83 ng/mL, nv &amp;lt;0,6 ng/mL). Abdominal magnetic resonance showed a 1.4 cm nodule in the pancreas tail. During hospitalization, she experienced Raynaud's phenomenon, leading to the diagnosis of Raynaud's disease (RD). Distal pancreatectomy was performed, confirming the diagnosis of insulinoma by immunohistochemistry. There was brief remission of the hypoglycemic episodes once they recurred two weeks later. As imaging tests did not show new pancreatic lesions, somatostatin analogue was begun, resulting in improvement for a few more weeks. Due to recurrent hypoglycemia and new seizures, she required continuous intravenous infusion of glucose during hospitalization. A new fasting test revealed hyperinsulinemic hypoglycemia (glycemia 42 mg/dL, insulin 43.3 mcU/mL), low C-peptide (0.5 ng/mL) and normal proinsulin (2.39 pmol/L, nv &amp;lt;5 pmol/L) values. Due RD, auto-immune hypoglycemia was excluded by negative anti-insulin antibodies. Insulinomatosis was also considered, as potential etiology, but review of surgical specimen excluded this hypothesis. After 4 months of hospitalization, due suspicious behavior, a review of her personal belongings revealed insulin vials and needles for injection. The patient confessed to applying insulin to simulate the symptoms, also revealing a history of childhood trauma and previous suicide attempts. After psychiatric evaluation, borderline personality disorder was identified, and Munchausen syndrome was considered. Since then, the patient did not require intravenous glucose with no recurrence of hypoglycemia. Conclusion: The investigation of hypoglycemia can be challenging, requiring appropriate diagnostic protocols. Even in patients who appear to have a well-defined diagnosis, as in our case with anatomopathological confirmation of insulinoma, it is always important to rule out factitious hypoglycemia. The incorrect diagnosis can lead to inappropriate invasive and surgical procedures with definitive consequences, such as exogenous pancreatic insufficiency and insulin-dependent diabetes mellitus. Presentation: 6/1/2024

B-104 Correlation of Anti-Centromere Antibodies (ACA) Detection by Indirect Immunofluorescence (IFA) on HEp-2 Cells and by ELISA Demonstrates High Concordance but Highlights Advantage of IFA

Abstract Background Anti-centromere antibodies (ACA), a type of anti-nuclear antibody (ANA) first identified as a discrete speckled pattern on indirect immunofluorescence assay (IFA), are a hallmark of systemic sclerosis (SSc), especially in its limited cutaneous form (lcSSc) or CREST (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly and telangiectasia). These mitosis-related autoantibodies mainly recognize three centromere proteins (CENP), CENP-A, CENP-B, and CENP-C, that comprise the kinetochore important to chromosome segregation, but more recently, at least three other CENP antigens have been identified (CENP-D, CENP-E and CENP-F). Anti-CENP-B is considered the main autoantibody, and many, if not most, ELISA utilize recombinant CENP-B such that antibodies to CENP antigens other than CENP-B are not detected. Here, an ELISA using both CENP-B and CENP-A is compared to the reference method, HEp-2 cell IFA, highlighting its high, but still less than 100%, sensitivity due to multiple centromere subcomponents. Methods Anti-centromere antibodies are determined in patient serum using the reference method, IFA on the HEp-2 cell substrate (Sprinter XL/EUROpattern®, Euroimmun, NJ) which is also the current method for standalone ACA testing as well as screening by selected ANA profiles designed for the rheumatology specialist. Here ACA IFA- positive and negative serum samples were further analyzed by enzyme immunosorbent assay (ELISA) utilizing recombinant CENP-A and CENP-B (QuantaLyzer® 3000, Werfen, CA). Results When compared, samples between ACA pattern by HEp-2 cell IFA and anti- centromere antibodies by ELISA yielded an agreement of 93.2%. McNemar’s Test Chi Square of p&amp;gt;0.999, with a relative sensitivity of 89.7% and a specificity of 100.0%. Conclusions This study demonstrated very high concordance between ELISA and accurate ACA pattern identification on HEp-2 IFA. The ELISA studied here identifies autoantibodies to both CENP-A and CENP-B where many other ELISA identify only anti-CENP-B. Although ACA are relatively specific for SSc, they have also been reported in systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), rheumatoid arthritis (RA), Sjogren Syndrome, Raynaud's phenomenon and in cancer in individuals with or without evidence of systemic autoimmune rheumatic disease (SARD). Of note, many other commercially available ELISA for anti-centromere antibodies identify only anti-CENP-B, but there at least four other known CENP antigen targets for autoantibodies causing centromere pattern on IFA. Furthermore, almost all laboratories use the ELISA for ACA on ANA panel (or other connective tissue disease) screening. Hence, it should be duly noted that these testing strategies will not detect autoantibodies to all anti-centromere antibodies. Only specialized ANA profiles designed for the difficult-to-diagnose autoimmune patient begin screening using the IFA method for anti-centromere and therefore, are capable of detecting autoantibodies to all CENP antigens. Laboratorians should advise clinicians of these diagnostic limitations especially as our knowledge about centromere subcomponents and their clinical associations increases.

Human papillomavirus nonavalent (HPV9) vaccination and risk of immune mediated diseases, myocarditis, pericarditis, and thromboembolic outcomes in Denmark: self-controlled case series study

ObjectiveTo assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent...