Raynaud's Phenomenon Research Articles

The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic skin hardening, which combines Raynaud's phenomenon and other vascular disorders, skin and internal organ fibrosis, immune disorders, and a variety of other abnormalities. Symptoms vary widely among individuals, and personalized treatment is sought for each patient. Since there is no fundamental cure for SSc, it is designated as an intractable disease with patients receiving government subsidies for medical expenses in Japan. Oxidative stress (OS) has been reported to play an important role in the cause and symptoms of SSc. HOCl-induced SSc mouse models are known to exhibit skin and visceral fibrosis, vascular damage, and autoimmune-like symptoms observed in human SSc. The antioxidant combination Twendee X® (TwX) is a dietary supplement consisting of vitamins, amino acids, and CoQ10. TwX has been proven to prevent dementia in humans with mild cognitive impairment and significantly improve cognitive impairment in an Alzheimer's disease mouse model by regulating OS through a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. We evaluated the effectiveness of TwX on various symptoms of HOCl-induced SSc mice. TwX-treated HOCl-induced SSc mice showed significantly reduced lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced highly oxidized protein products (AOPP) in serum and suppressed Col-1 gene expression and activation of B cells involved in autoimmunity. These findings suggest that TwX has the potential to be a new antioxidant treatment for SSc without side effects.

Cardiopulmonary phenotype in systemic sclerosis associated pulmonary hypertension

IntroductionPulmonary hypertension (PH) associated with systemic sclerosis (SSc) increases morbidity and mortality. Cardiopulmonary comorbidities, as per the 2021 PH consensus, play a role in the choice of therapy between monotherapy and combination therapy. MethodsA cross-sectional study was conducted in patients with SSc based on the 2013 ACR/EULAR criteria or very early disease (VEDOSS 2011). PH was considered if they met the following criteria: pulmonary artery systolic pressure (PASP)>39mmHg or peak tricuspid regurgitation velocity (PTRV)>3.4m/s, PASP between 33 and 39mmHg or PTRV between 2.9 and 3.4m/s plus two additional findings suggestive of PH. PH was classified as type 2 if LVEF<50% or moderate to severe diastolic dysfunction was present; type 3 if extensive interstitial disease on tomography>20% or forced vital capacity (FVC)<75%; type 4 if abnormalities related to embolism were detected on scintigraphy or tomography. If patients did not meet these criteria, they were classified as type 1 PH. Complete data on cardiopulmonary risk factors and other factors were required. The frequency of these factors in the population and differences between groups based on risk factors were estimated. ResultsA total of 228 patients were selected. Three had type 2 PH, 24 had type 3, and 40 had type 1 PH, with the majority (75%) having at least one cardiopulmonary risk factor, and 47.5% having more than one. Mild diastolic dysfunction (25%) and hypertension (35%) were the most prevalent. In the type 1 PH group, those with risk factors experienced an increase in the number of years with Raynaud's phenomenon, anticentromere antibodies, and gastrointestinal symptoms (p<0.05). ConclusionIn patients with PH, 75% have one, and 45% have two or more risk factors.

Clinical and serological characteristics of anti-Ro/SS-A and anti-La/SS-B negative primary Sjögren's syndrome: a comparative study.

This study aimed to describe the clinical spectrum of primary Sjögren's syndrome (pSS) patients with anti-Ro/SS-A and anti-La/SS-B negativity. From a single-center study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, those with triple seronegativity anti-Ro/SS-A (anti-Sjögren's-syndrome-related antigen A autoantibody), anti-La/SS-B (anti-Sjögren's-syndrome-related antigen B autoantibody), rheumatoid factor (RF) (-) and antinuclear antibody (ANA)(+)] or [anti-Ro/SS-A(-), anti-La/ SS-B(-), RF(+) and ANA(-)] and quad¬ruple seronegativity [anti-Ro/SS-A(-), anti-La/SS-B(-), RF(-) and ANA(-)] were identified retrospectively. Clinical, serological, and laboratory features were compared. A comparison between triple and quadruple seronegative pSS patients was also performed. We included 184 patients (168 women, 16 men) with a mean age at diagnosis of 50.1±13.1 years. The most common subjective presenting features at the time of the diagnosis were dry mouth (94.5%) and dry eye (91.3 %). ANA positivity was 57.0%, and RF positivity was 30.4%. Salivary gland enlargement, arthritis, Raynaud's phenomenon, vasculitis, interstitial lung disease (ILD), neurological involvement, primary biliary cholangitis (PBC), lymphopenia, and thrombocytopenia were observed in ANA+ and RF+ patients but not in seronegative patients (p<0.0001). Arthritis was observed most frequently in RF-positive patients and secondly in ANA-positive patients, whereas arthritis was not observed in seronegative patients (p<0.0001). Autoimmune thyroiditis was present in 65 patients (35.0%), 84.6% of these patients were ANA positive while 12.3% were ANA negative (p=0.0014), RF positivity was 30.7% while RF negativity was 6.15% (p=0.001), 23.0% were both ANA and RF positive while 12.3% were seronegative (p<0.002). Cryoglobulinemia, renal disease, and lymphoma were not observed in any of the patients. We confirm the strong influence of immunological markers on the phenotype of primary SS at diagnosis.

Clinical Characteristics and Outcomes of Interstitial Lung Disease in Primary Sjögren's Syndrome: A Retrospective Cohort Study.

To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response. All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed. Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders. ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.

Assessing hand and global disability in a cohort of Algerian patients with systemic sclerosis: Construct validities of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire.

The study aimed to assess the construct validity of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire in Algerian patients with systemic sclerosis. Consecutive Algerian patients who fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis were included. In addition to disease characteristics, global disability and hand disability were assessed using the Arabic Health Assessment Questionnaire and the Arab Hand Function Index, respectively. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. The scale reliability was assessed using the Cronbach's alpha. We evaluated 100 systemic sclerosis patients (83 females) of mean ± standard deviation age 46.7 ± 12.3 years, including 59 limited cutaneous systemic sclerosis and 41 diffuse cutaneous systemic sclerosis. Raynaud's phenomenon was detected in 99 patients and digital ulcers in 25. Gastrointestinal tract involvement and interstitial lung disease were detected in 86/100 (86%) and 46/72 (63.9%) patients, respectively. Anti-topoisomerase I and anti-centromere antibodies were detected in 33/76 (43.4%) and 23/76 (30.3%) patients, respectively. The Arab Hand Function Index had a good construct validity with a total score explaining 61% of the variance of the Arabic Health Assessment Questionnaire which also had a good construct validity. Factor analysis of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire items extracted two factors explaining 64% of the variance for the Arab Hand Function Index and one factor explaining 55% of the variance for the Arabic Health Assessment Questionnaire. The Arab Hand Function Index and the Arabic Health Assessment Questionnaire were reliable questionnaires with a Cronbach's alpha >0.8. In Algerian patients with systemic sclerosis, Arab Hand Function Index and Arabic Health Assessment Questionnaire have a good construct validity and reliability.

Platelet-rich plasma for the treatment of scleroderma-associated ulcers: a single-center experience and literature review.

Systemic sclerosis (SS) is a complex connective tissue disease characterized by vasculopathy and progressive fibrosis, primarily considered an autoimmune disorder. SS can affect multiple organs and tissues, including the skin, respiratory, gastrointestinal, genitourinary, cardiovascular, and musculoskeletal systems. Skin involvement is common, and SS-related ulcers, especially digital ulcers, occur in roughly 50% of patients. These ulcers not only cause pain but also significantly impact patients' quality of life, and in severe cases, they can lead to infection, gangrene, and amputation. The search for novel therapies for scleroderma-related ulcers remains an ongoing research area. Platelet-rich plasma (PRP) has been investigated as a potential treatment for difficult-to-heal ulcers, including diabetic, pressure, and vascular ulcers. In this study, we share our experience in treating scleroderma ulcers with PRP. Ten patients with confirmed SS and chronic skin ulcers lasting at least six weeks, which had not responded to conventional treatments, were selected for the study. Homologous PRP gel was prepared and applied once a week for up to eight weeks. The ulcers were documented photographically before and after PRP treatment, and pain levels were assessed using a visual analog scale (VAS). We also conducted a systematic review of the literature focusing on the use of PRP in the setting of SS. The results from our casuistry showed that the ten patients, including eight females and two males with a median age of 52.5 years, had ulcer sizes ranging from 0.78 cm2 to 28.26 cm2. The ulcers were located on fingers, legs, and heels, and they were associated with various forms of SS, including limited and diffuse cutaneous involvement. Raynaud's phenomenon was prevalent, and two patients exhibited organ involvement. The average ulcer size at the end of PRP treatment decreased significantly, with a 78% reduction in ulcered area. Pain levels also markedly improved, as indicated by a reduction in VAS scores. With regards to systematic revision of literature, we retrieved 45 cases of SS treated with PRP-based therapeutic regimes. However, only a minority of them (n=16) underwent PRP treatment for the treatment of SS-related ulcers. An improvement in wound size and pain has been documented in all cases. Taken together, these data highlight the potential benefits of using homologous PRP in the treatment of scleroderma ulcers, emphasizing its positive impact on ulcer size reduction and pain relief.

Mixed connective tissue disease with juvenile onset: results of a retrospective single-center study

Mixed connective tissue disease (MCTD) is one of the very rare systemic autoimmune diseases; it accounts for 0.1–0.6% of cases in pediatric rheumatologists' practices. MCTD is characterized by a broad spectrum of clinical manifestations and a high frequency of extremely unspecific symptoms at the onset, with the overall picture of the disease forming slowly and gradually. The diagnosis is often delayed and confirmed only at an advanced stage of organ dysfunction with the development of irreversible changes.Objective: to identify a group of patients fulfilling the criteria for MCTD in an open, single-center, continuous retrospective study among anti-ribonucleoprotein (anti-RNP) antibody-positive patients and to analyze their demographic, clinical and laboratory characteristics and therapy.Material and methods. All anti-RNP-positive patients admitted to the pediatric department of V.A. Nasonova Research Institute of Rheumatology from 2019 to 2023 and meeting at least one of the variants of the MCTD criteria (Kasukawa, Alarcуn-Segovia, Kahn and Sharp criteria) were included in the study.Results and discussion. 18 (56.25%, 17 girls and 1 boy) of 32 anti-RNP-positive patients fulfilled criteria for MCTD. Patients most frequently fulfilled a combination of criteria – Sharp and Kahn (n=8) or Alarcуn-Segovia and Kahn (n=8). The median age of onset of MCTD was 12.2 [9.7; 13.9] years. The most common clinical manifestations were arthritis (100%), various skin lesions (94.4 %), Raynaud's phenomenon (88.9%), lymphadenopathy (72.2%) and general constitutional disorders (50%). Sjögren's syndrome (SS) was diagnosed in 17 (94.4%) patients. All patients had antinuclear factor (ANF) 1/1280, and the anti-RNP level was &gt;200 U/ml. There were also antibodies against double-stranded DNA (n=5), Ro- (n=4) and Sm- (n=5) antigens. An IgM rheumatoid factor was detected in 6 patients and hypergammaglobulinemia in 10 patients. Capillaroscopic changes in the nailfold with predominant scleroderma type were found in 77.8% of patients. The most common combination was of Raynaud's phenomenon, arthritis, SS, lymphadenopathy and hypergammaglobulinemia (50%). All patients received glucocorticoids, 9 – hydroxychloroquine, 8 – methotrexate, 3 – mycophenolate mofetil, 1 – cyclophosphamide, 1 – azathioprine. Biologic DMARDs (bDMARDs) were prescribed to 12 (66.7%) patients: 3 – rituximab, 8 – abatacept, 1 – belimumab, with an acceptable safety profile and initial efficacy.Conclusion. Most patients in the study met the Kahn criteria. Only 2 patients met all variants of the criteria, which indicates the need to use a combination of criteria when a MCTD is suspected. A combination of Raynaud's phenomenon, arthritis, SS, lymphadenopathy and hypergammaglobulinemia was observed in half of patients with MCTD. The presence of Raynaud's phenomenon and high ANF titer in children with rheumatic diseases, especially with a polymorphic clinical picture, requires the inclusion of MCTD in differential diagnosis. Preliminary results indicate the safety of the use of biologic drugs in children with MCTD.

Clinical case of systemic sclerosis in a male patient: gender differences and possibilities of capillaroscopy

A patient with a subacute course of systemic sclerosis (SSc) and a three-phase Raynaud's phenomenon at the onset of the disease is described. The diagnosis was made in accordance with the ACR/EULAR 2013 criteria. Within 8 months of disease onset, the patient developed the classic picture of SSc with multiple organ involvement, and nailfold capillaroscopy showed signs of the active stage of scleroderma angiopathy. The factors for an unfavorable course of SSc were analyzed.

Interstitial lung disease and associated factors in patients with Sjögren's syndrome.

Interstitial lung disease (ILD) is a common pulmonary manifestation of Sjögren's syndrome (SjS) and associated with an increased risk of death. Early detection and treatment of ILDs and knowing the risk factors are very important for prognosis in rheumatic diseases. This study was performed to determine ILD and associated factors in patients with SjS. Four hundred three SjS patients were evaluated in this cross-sectional cohort study. Clinical, laboratory, serological, and imaging features were compared of patients with and without pulmonary involvement. Logistic regression analyses were used to identify risk factors for lung involvement and to identify independent risk factors. Thirty-five (8.7%) of SjS patients had ILD and 368 (91.3%) had no ILD. The presence of Raynaud's phenomenon was significantly more common in ILD. The geriatric age group over the age of 65years (OR 8198; 95% CI 3788-17,742; p < 0.001), Raynaud's phenomenon (OR 17,852; 95% CI 6155-51,779; p < 0.001), and smoking (OR 3598; 95% CI 1495-8657; p = 0.003) were risk factors to be associated for ILD in the multivariable analysis. The most common abnormality was non-specific interstitial pneumonia in 20 patients (57.1%) and usual interstitial pneumonia in 15 (42.9%) patients. The distribution of male patients compared to female patients was higher in patients with lung involvement than in patients without lung involvement. This may be related to older age, higher smoking rate, and longer nicotine consumption in men. Age, smoking, and severity of lung involvement are more important than inflammation status and autoantibodies for prognosis.

Capillaroscopic differences between primary Raynaud phenomenon and healthy controls indicate potential microangiopathic involvement in benign vasospasms.

For primary Raynaud phenomenon (PRP), an otherwise unexplained vasospastic disposition is assumed. To test the hypothesis of an additional involvement of distinct ultrastructural microvascular alterations, we compared the nailfold capillary pattern of patients with PRP and healthy controls. A total of 120 patients with PRP (with a median duration of vasospastic symptoms of 60 [IQR: 3-120] months) were compared against 125 controls. In both groups, nailfold capillaroscopy was performed to record the presence of dilatations, capillary edema, tortuous capillaries, ramifications, hemorrhages, and reduced capillary density and to determine a semiquantitative rating score. Further, the capacity of finger skin rewarming was investigated by performing infrared thermography in combination with cold provocation. Unspecific morphologic alterations were found in both, PRP, such as controls, whereby the risk for PRP was four times as high in the presence of capillary dilations (CI: 2.3-7.6) and five times as high if capillary density was reduced (CI: 1.9-13.5). Capillary density correlated with thermoregulatory capacity in both hands in the PRP group, but not in controls. In addition, a negative correlation between the microangiopathy score and the percentage degree of rewarming in both hands was found for patients with PRP only. We found specific differences within the microvascular architecture between patients with PRP and controls. As a conclusion, PRP may not be an entirely benign vasospastic phenomenon, but might be associated with subtle microcirculatory vasculopathy. In addition, we suggest that the implementation of a scoring system might serve as guidance in the diagnostic process at least of patients with long-standing PRP.

Advanced Raynaud's disease: A vascular medicine-initiated team-based approach and nationwide cohort analysis.

Advanced Raynaud's disease: A vascular medicine-initiated team-based approach and nationwide cohort analysis.

Clinical and immunological characteristics and prognosis of patients with autoantibody negative dermatomyositis: a case control study.

Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM)clinical phenotypes. The aim of this study is to explicate the clinical andimmunologicalfeatures of MSAs-negative DM patients. A total of 515 individuals diagnosed with DM was screenedfrom 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed. MSAs-negative DMpatients were categorized into two groups: MAAs-negative(MSAs (-)/MAAs (-)) groupand MAAs-positive (MSAs (-)/MAAs (+))group. The percentage of Raynaud's phenomenon (P=0.026) was higher in the MSAs (-)/MAAs (+) DM patients than the MSAs-positiveDM patients and MSAs (-)/MAAs (-) DMpatients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (-)/MAAs (+) group had a higher proportion of organizing pneumoniaand usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among totalCD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onsetage, higher level ofcarcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients. Compared with MSAs-positive group,MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis. Key Points MSAs-negative DM patients exhibited distinct characteristics in comparison with MSAs-positive DMpatients: • The MSAs (-)/MAAs (+) DM patientsdemonstrated a higher prevalence of organizing pneumonia (OP)and usual interstitial pneumonia (UIP), and elevated eosinophil counts in bronchoalveolar lavage fluid. • CEA levels were lower in MSAs-negative patients compared with MSAs-positive patients. • Elevated counts of lymphocytes and CD16+CD56+ NK cells were identified in the MSAs-negativepatients. Additionally, proportions of CD4+TNFα+, CD4+IFNγ+, and CD4+IL-2+ cells among total CD4+ T cells were higher in the MSAs-negative DM patients compared with DM MSAs-positive DM patients. • MSAs-negative DMpatients had a more favorable prognosis than MSAs-positive DMpatients. A multivariable regression analysis revealed the advanced onsetage, highCEA levels, and RP-ILD were risk factors for mortality in DM patients.

Patients’ perspectives on systemic sclerosis-related Raynaud's phenomenon in the feet: A qualitative study from the OMERACT Foot and Ankle Working Group

ObjectiveTo explore, from patients’ perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients. MethodsForty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance. ResultsTwenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants’ lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery. ConclusionsThis large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients’ lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases.

Digital gangrene in systemic sclerosis patients: not only due to the microvascular disease.

This study aims to investigate the characteristics, risk factors, and outcomes of digital gangrenes in SSc patients, and to identify whether vasculitis is one of the causes for digital gangrene. A retrospective case-control study was performed from February 2003 to April 2021. Forty-three SSc patients with digital gangrene admitted to Peking Union Medical College Hospital were included. One-hundred forty-six age- and sex-matched SSc patients without gangrene were selected as controls during the same period. Univariate and multivariate logistic regression analysis was used to determine risk factors. Among 43 SSc patients with gangrene, 93.0% had Raynaud's phenomenon (RP) and 32.6% had current or previous digital ulcers (DU). SSc patients with digital gangrene had more ESR elevation (54.8% vs. 34.9%, p = 0.020) and higher level of high-sensitive C reactive protein (median 7.2mg/L vs. 1.8mg/L, p = 0.045) compared with controls. In the multivariable logistic regression analysis, smoking history (OR 4.119, p = 0.037), anti-centromere antibody positivity (OR 3.542, p = 0.016), anti-neutrophil cytoplasmic antibody positivity (OR 22.605, p = 0.037), and anti-phospholipid antibody positivity (OR 16.563, p = 0.001), as well as elevated ESR (OR 2.524, p = 0.038) were identified as independent risk factors for gangrenes. Most (79.1%) cases were treated with combination of immunosuppressive and vasodilating therapy, and four cases also got remised after treatment of only glucocorticoid and immunosuppressive agent. Smoking history; positive-ACA, ANCA, and anti-phospholipid antibodies; and increased ESR were independent risk factors for digital gangrenes in SSc. Vasculitis and macrovascular disease may contribute to the progression of digital gangrenes. Key Points •18.6% of SSc patients with digital gangrene had macrovascular stenosis. •Smoking, positive-ACA, ANCA, aPL, and increased ESR were indicators for digital gangrenes in SSc. •Vasculitis and macrovascular disease may involve in the pathogenesis.

Development of a core domain set for nailfold capillaroscopy reporting

BackgroundThe peripheral microangiopathy may be well evaluated and studied by nailfold capillaroscopy (NFC) which is a safe and non-invasive technique. NFC has been reported to have both diagnostic and prognostic values in patients presenting with Raynaud's phenomenon. ObjectiveThe overarching objective of this work was to make a consensus on what domains should be included in a capillaroscopy report and that it can be used in daily clinical practice and clinical research in the area of rheumatology. MethodsA Delphi questionnaire was developed regarding capillaroscopy report from a literature review and expert consensus. The first Delphi round included 14 core areas, its 18 domains with 50 subdomains, derived from a systematic literature review. The level of evidence was determined for each core set using the Oxford Centre for Evidence-based Medicine (CEBM) system. Nine response categories have been set per each item ranging between 1 and 9. Round 2, aimed to reach preliminary consensus “in” or “out” for domains. It included all items that were rated “critical” by at least 80% of the participants as well as any new domains proposed in round 1. ResultsThe participants to the first, and second round were 11 experts. Fourteen domains were discussed in the two rounds. At the end of the survey, the final report template of NFC in rheumatology reached a consensus. ConclusionA nailfold capillaroscopy report template has been developed by this study, based on outcomes of a Delphi process, by international participants panel. All domains met the 80% voting threshold set in this work. The reporting template can be used for both clinical research as well as day to day practice to provide guidance and standardize the NFC reporting.

Serum biomarkers in patients with hand-arm vibration injury and in controls

Hand-arm vibration injury is a well-known occupational disorder that affects many workers globally. The diagnosis is based mainly on quantitative psychophysical tests and medical history. Typical manifestations of hand-arm vibration injury entail episodes of finger blanching, Raynaud’s phenomenon (RP) and sensorineural symptoms from affected nerve fibres and mechanoreceptors in the skin. Differences in serum levels of 17 different biomarkers between 92 patients with hand-arm vibration injury and 51 controls were analysed. Patients with hand-arm vibration injury entailing RP and sensorineural manifestations showed elevated levels of biomarkers associated with endothelial injury or dysfunction, inflammation, vaso- or neuroprotective compensatory, or apoptotic mechanisms: intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1); thrombomodulin (TM), heat shock protein 27 (HSP27); von Willebrand factor, calcitonin gene-related peptide (CGRP) and caspase-3. This study adds important knowledge on pathophysiological mechanisms that can contribute to the implementation of a more objective method for diagnosis of hand-arm vibration injury.

Epidermodysplasia verruciformis arising in a female with systemic lupus erythematosus: a rare case from Syria

Introduction and importance: Epidermodysplasia verruciformis is a rare autosomal recessive genodermatosis. Clinical manifestations might be helpful in the diagnosis of this disease. However, the final diagnosis is made after a genetic and histological study. Acquired epidermodysplasia verruciformis is a form of epidermodysplasia verruciformis described in patients with compromised cell-mediated immunity. Case presentation: A 42-year-old female with a history of a pain and itch on the soles and palms started a year ago. There were multiple flat papules on the dorsal hands, scarring alopecia, malar rash, oral ulcers, Raynaud phenomenon, and palpable purpura. A histological examination confirmed the diagnosis of epidermodysplasia verruciformis. Clinical discussion: Epidermodysplasia verruciformis is an uncommon disease that affects the immune system. The coexistence of systemic lupus erythematosus and epidermodysplasia verruciformis is rarely reported in the medical literature. This paper reports a rare case in which these two diseases have coexisted. Conclusion: This publication aims to document this rare case and highlight the ideal criteria in diagnosing and treating epidermodysplasia verruciformis.

Outcomes of men with high-risk biochemically recurrent prostate cancer who suspended enzalutamide monotherapy treatment in the phase 3 EMBARK study.

15 Background: In the 3-arm EMBARK trial, enzalutamide (enza) + leuprolide acetate (leuprolide) and enza monotherapy (mono) showed statistically superior and clinically meaningful improvements in metastasis-free survival (MFS) vs placebo + leuprolide (alone) in patients (pts) with high-risk biochemically recurrent (BCR) prostate cancer. Based on serum prostate-specific antigen (PSA) response, treatment (tx) was suspended at week 37 in 304 (85.9%) pts in the enza mono arm and 240 (67.8%) in the leuprolide-alone arm; pts who did not meet suspension criteria continued tx. Outcomes with enza mono vs leuprolide alone by tx suspension status are presented. Methods: EMBARK is a double-blind phase 3 study of pts with high-risk BCR (i.e., PSA doubling time (PSADT) ≤9 months and PSA ≥2 ng/mL above nadir post-radiotherapy [RT] or ≥1 ng/mL after radical prostatectomy [RP] ± postoperative RT). Pts were randomized (1:1) to enza mono (160 mg/day, open-label) or leuprolide alone (22.5 mg every 12 weeks). PSA &lt;0.2 ng/mL at week 36 triggered tx suspension at week 37; tx restarted when PSA reached ≥2 ng/mL or ≥5 ng/mL for pts with or without primary RP, respectively. The proportion of pts with undetectable PSA 2 years after tx suspension was a secondary endpoint. MFS (by blinded independent central review) was analyzed descriptively in each tx arm by suspension status. P-values were nominal. Results: In the suspension group, the 3-year MFS rate (95% CI) was 88.1% (83.8–91.4%) for enza mono and 90.0% (85.3–93.2%) for leuprolide alone; there was no difference in MFS (hazard ratio [HR] 0.840, 95% CI 0.575–1.226; P=0.3659). In the no suspension group, 3-year MFS rates were 88.5% (68.5–96.2%) and 66.9% (55.4–76.1%), respectively; MFS was longer with enza mono vs leuprolide alone (HR 0.340, 95% CI 0.118–0.985; P=0.0378). In the suspension group vs the no suspension group, a greater proportion had received prior RP (enza mono: 78.9 vs 41.9%; leuprolide alone: 78.3 vs 52.2%) or RP and RT (enza mono: 50.7 vs 16.1%; leuprolide alone: 55.0 vs 38.0%), while baseline median PSADT was similar (enza mono: 4.9 vs 5.9 months; leuprolide alone: 5.0 vs 4.8 months). The proportion (95% CI) of pts with undetectable PSA 2 years after tx suspension was 4.6% (2.5–7.6%) for enza mono and 9.6% (6.2–14.0%) for leuprolide alone ( P=0.0326). Conclusions: In pts with high-risk BCR who suspended tx, the tx effect on MFS with enza mono was not different compared with leuprolide alone, though more pts reached tx suspension criteria with enza mono. However, in the no suspension group, enza mono prolonged MFS vs leuprolide alone, though the number of MFS events was limited (n=4). Pts with prior RP were also more likely to reach the PSA threshold for tx suspension. Few pts who suspended tx had undetectable PSA after 2 years, regardless of tx. Clinical trial information: NCT02319837 .

A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's.

Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP. Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory endpoints included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites. Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). Mean weekly number of RP attacks (baseline; vipoglanstat 14.4[SD 6.7], placebo 18.2[12.6]) decreased by 3.4[95% CI -5.8;-1.0] and 4.2[-6.5;-2.0] attacks per week (p= 0.628) respectively. All patient reported outcomes improved, with no difference between the groups. Mean change in recovery of peripheral blood flow after cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in urine. Vipoglanstat was safe and well tolerated. Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role.

Nailfold dermoscopy predicts the absence of a capillaroscopy sclerodermic pattern: The multicentre, prospective VASCUL-R trial.

Nailfold capillaroscopy is recommended to diagnose primary or secondary Raynaud's phenomenon (RP). Capillaroscopy is normal in primary RP, which is the most frequent. Screening for RP capillary anomalies with nailfold dermoscopy has been promising. To determine whether normal nailfold dermoscopy-based on the absence of five criteria that define a sclerodermic pattern-is able to predict normal capillaroscopy with good positive-predictive value (PPV). Prospective, 2-phase (monocentre and multicentre) study on patients at first consultation for RP undergoing nailfold video capillaroscopy (NVC) and nailfold dermoscopy by two different 'blinded' trained observers, respectively, a vascular specialist and a dermatologist, not familiar with capillaroscopy. The five criteria noted were as follows: disorganization, megacapillaries, low capillary density, avascular areas and haemorrhages. Based on 105 patients, the dermoscopy PPV for a normal NVC was 100% (p = 0.015), with 37.9% sensitivity, when no criterion was observed. Excluding haemorrhages, the PPV remained 100% (p < 0.0001), with sensitivity rising to 73.7% and 100% specificity. Normal nailfold dermoscopy with the absence of four easy-to-observe criteria predicts normal NVC with an excellent PPV.