UNASSIGNED: To investigate the hypotheses that in patients with SSc, the temperature gradient between the dorsum of the foot and toes (distal-dorsal difference [DDD]) is \'more negative\' (toes cooler) than in healthy controls, is greatest along the first (great) toe and that the severities of thermographic abnormalities in the feet and hands are correlated.
UNASSIGNED: Thermographic images of the dorsum of each hand and foot were captured using a thermal camera attached to an iPhone in 40 patients with SSc and 20 healthy controls. DDDs along the fingers (index, middle, ring and little) and toes (great toe and \'others\') were measured.
UNASSIGNED: There was a non-significant trend for the great toes to be colder in patients with SSc than in controls. The mean great toe DDD was more negative in patients (right: -2.89°C, left: -2.91°C, mean: -2.90°C) than in controls (right: -2.36°C, left: -2.42°C, mean: -2.39°C) (P = 0.37 for mean values). Patients\' great toes were colder than \'other\' (lesser) toes (right: -2.58°C, left: -2.63°C), although not significantly. In patients with SSc, finger and great toe temperature gradients were correlated (r = 0.406, ρ = 0.01).
UNASSIGNED: Our findings suggest that the great toe is the coldest in patients with SSc and that patients with the coldest fingers tend to have the coldest toes. Severe RP symptoms in the hands should prompt podiatry assessment and foot care education. Mobile phone thermography is a convenient tool for assessing the digital vasculature but first requires validation in larger studies with a longitudinal component.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

暂无摘要。

OBJECTIVE: Raynaud\'s phenomenon, one of the major symptoms of systemic sclerosis (SSc), is difficult to treat. Although it is empirically considered that warming is a beneficial technique, there is no supportive evidence. We conducted a multicentre study to evaluate whether continuous heating of the arm alleviates Raynaud\'s phenomenon in SSc.
METHODS: A pair of disposable warmers was applied to the upper arm near the elbow of patients with SSc. Two weeks of non-warmer application were followed by 2 weeks of warmer application, which was repeated twice. The Raynaud Condition Score (RCS), number of episodes, and duration of Raynaud\'s phenomenon were recorded. The differences in the mean RCS, frequency, and duration of Raynaud\'s phenomenon between the warmer application and non-application periods were analysed.
RESULTS: Twenty-eight patients were included in the analysis. The average RCS was 1.98 and 2.66 during the warmer application and non-application periods, respectively. The change between the two periods was statistically significant by paired t-test. In addition, the frequency and total duration of Raynaud\'s phenomenon in the warmer application period were significantly lower than those in the non-application period.
CONCLUSIONS: Heating of the upper arm near the elbow is effective in alleviating Raynaud\'s phenomenon in SSc.

Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects predominantly women in the childbearing years. Patients may seek complementary therapies to manage their health and to reduce symptoms. However, to our knowledge, no studies have explored the association between clinical manifestations of SLE and complementary therapies. Therefore, this study aimed to investigate the association of complementary therapies with common clinical manifestations in Taiwanese female patients with SLE. Materials and Methods: A cross-sectional study was conducted at a regional teaching hospital in southern Taiwan. Outpatients from the rheumatology clinic who met the inclusion criteria were consecutively recruited. Demographic data, clinical manifestations of SLE, and types of complementary therapy use were determined using paper-based questionnaire. Multiple logistic regression analyses were conducted to investigate the use of complementary therapies associated with clinical manifestations of SLE. Results: Of the 317 female patients with SLE, 60.9% were 40 years or older. The five SLE clinical manifestations with the highest prevalence were Raynaud’s phenomenon (61.2%), photosensitivity (50.2%), Sjögren’s syndrome (28.4%), arthralgia and arthritis (22.1%), and renal involvement (14.5%). Multiple logistic regression analyses revealed that Raynaud’s phenomenon was significantly associated with fitness walking or strolling (adjusted odds ratio [aOR] 1.77; p = 0.027) and fish oil supplements (aOR 3.55, p < 0.001). Photosensitivity was significantly and inversely associated with the use of probiotics (aOR 0.49; p = 0.019). Renal involvement was significantly associated with the use of probiotics (aOR 2.43; p = 0.026) and visit to the Chinese medicine department in a hospital (aOR 3.14, p = 0.026). Conclusions: We found that different clinical manifestations of SLE were associated with the use of different complementary therapies. Health care providers should have up-to-date knowledge of common complementary therapies and be ready to provide evidence-based advice to patients with SLE.

UNASSIGNED: Raynaud\'s phenomenon (RP) and digital ulcers (DU) are frequent manifestations of Systemic Sclerosis (SSc). Despite being very common in SSc patients, both conditions have proven to be notoriously difficult to study. There are very few available approved drugs with varying efficacy. It has been shown that the presence of DU is associated with increased whole blood viscosity (WBV). Rheopheresis (RheoP) is an extracorporeal apheresis technique used to treat microcirculatory disorders by improving blood viscosity. Improved blood flow and wound healing after RheoP treatments have been reported in single case reports.
UNASSIGNED: We report the clinical trial protocol of \"A randomized controlled prospective single-center feasibility study of Rheopheresis for Raynaud\'s syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT).\" RHEACT aims to investigate the efficacy of RheoP on the Raynaud Condition Score (RCS) as the primary efficacy outcome measure after 16 weeks from baseline. Thirty patients will be randomized in a 1:1:1 ratio to one of two RheoP treatment groups or assigned to the standard of care (SoC) control group (intravenous iloprost). Secondary endpoints include changes in DU, changes in nailfold video capillaroscopy and patient-reported-outcomes (Scleroderma Health Assessment Questionnaire, FACIT-Fatigue, and the Disability of Arm, Shoulder, and Hand, quick version).
UNASSIGNED: Apheresis techniques have been investigated in SSc but mainly in observational, retrospective studies, or single case reports. RheoP is a pathophysiologically driven potential new therapy for heavily burdened patients with SSc-associated secondary RP with or without DU.
UNASSIGNED: The study was registered at clinicaltrials.gov (Identifier: NCT05204784). Furthermore, the study is made publicly available on the website of the German network of Systemic Sclerosis \"Deutsches Netzwerk Systemische Sklerodermie (DNSS).\"

OBJECTIVE: Raynaud\'s phenomenon (RP) is a peripheral vascular disorder that frequently occurs in systemic sclerosis (SSc). Although therapeutic heating seems reasonable given that RP is elicited by cold stimuli, the effects of heating are still unclear. We examined the effects of heating applied on various body parts in SSc patients with RP of fingers.
METHODS: Fourteen SSc patients heated their neck, elbows, and wrists with disposable heating pads for 1 week each. The visual analogue scale (VAS) for RP during each heating period was compared with that of each 1-week pre-treatment interval. On the day after the expiration of each heating period, their finger temperature, the finger blood flow, and angiogenesis-related factors (vascular endothelial growth factor, endostatin, angiopoietin-1, and angiopoietin-2) obtained from the cubital vein and fingertip were measured.
RESULTS: The mean VAS was significantly reduced during the heating of the neck and elbows. Fingertip blood samples showed significantly increased angiopoietin-1 after each of the heating periods and increased endostatin after wrist heating. After the termination of heating, changes in finger temperature or blood flow could not be detected.
CONCLUSIONS: Heating the neck or elbows can alleviate RP in SSc. The heat up-regulates angiopoietin-1 in the fingers.

Vasospasm is one of the important causes of morbidity in free flap and replantation surgery. In secondary Raynaud\'s phenomenon, nearly half of the patients experience digital ulceration, pain and loss of function at least once in their lifetime. The aim of this study is to investigate the vasodilation effect of ethanol-mediated chemical denervation on peripheral vessels by topical administration. In this study, 27 Wistar albino male rats weighing 250-300 grams were used. The rats were randomly divided into three groups: saline (group S, n = 8), lidocaine (group L, n = 9) and 96% ethanol (group E, n = 9). According to group, 0.1 mL saline, 0.1 mL lidocaine and 0.1 mL ethanol were applied around the rat femoral neurovascular bundle. After the application, on the 0th day and 3th weeks, femoral artery and vein diameters were measured. After 3. weeks, histopathological samples from femoral artery, vein and nerve were evaluated. On the 0th day, the mean diameter of the femoral artery and vein was similar in group E and L and higher than group S. After three weeks, the vasodilatation effect of ethanol was increased in group E. In Group L and S, the vasodilatation effect was lost. Histopathological examination showed that ethanol significantly caused perivascular inflammation and nerve degeneration compared to other agents and did not cause endothelial damage. Vasodilatation obtained by ethanol is a rapid onset and long-lasting effect. It is also inexpensive and effective for peripheral vasodilatation.

The aim of this observational study was to investigate the evolution of scleroderma microangiopathy throughout different nailfold videocapillaroscopy (NVC) patterns (\'early\', \'active\', \'late\') as well as the prevalence of organ involvement in SSc patients during a 12-year follow-up.
Thirty-four SSc patients showing at baseline (first capillaroscopic analysis) the \'early\' NVC pattern of microangiopathy were enrolled and followed for 12 years (s.d. 2). Complete NVC analysis and clinical and serological findings were collected. Patients were in a standard therapeutic care setting. Statistical analysis was carried out by non-parametric tests.
After a 12-year follow-up, the \'early\' NVC pattern changed from baseline in 76% of the patients. The NVC pattern was found to be \'active\' in 9 patients (26%), \'late\' in 13 (38%) and characterized by non-specific capillary abnormalities in 4 (12%). In the subgroup whose microangiopathy progressed from the \'early\' to the \'late\' NVC pattern, the median time of progression from the \'early\' to the \'active\' pattern was significantly shorter (11 months) when compared with patients who progressed from the \'early\' to the \'active\' NVC pattern (55 months) (P = 0.002). The median time of progression between NVC patterns was significantly shorter in SSc patients showing either a nucleolar ANA pattern or Scl70 autoantibodies (P = 0.048). Organ involvement was progressively greater in SSc patients with \'early\', \'active\' and \'late\' NVC patterns, respectively.
This longitudinal study confirms over a 12-year follow-up the evolution of specific NVC patterns associated with the progressive severity of organ involvement in SSc patients in a standard clinical care setting.

Raynaud\'s phenomenon (RP) is a clinical disorder characterized by recurrent, reversible episodes of digital vasospasm. RP can be classified as primary (pRP) or secondary, depending on whether it occurs as a benign condition (not disease-associated) or is associated with other diseases, mainly of the connective tissues. In both cases, it can be triggered by environmental factors, as indicated by the increased incidence of pRP episodes following exposure to cold, vibration injury or chemicals. The purpose of this prospective case-control study was to assess, in an Italian cohort of 132 pRP patients, the association of the phenomenon with demographic, lifestyle habits, environmental and work-related factors. Compared to healthy controls, pRP was found to be inversely associated with the use of contact lenses (OR = 0.4; p = 0.004) and of chlorous-based disinfectants (OR = 0.3; p < 0.001) and directly associated with the presence of prosthesis implants (OR = 5.3; p = 0.001) and the use of hydrogen peroxide-based compounds (OR = 2.6; p = 0.002), suggesting that the latter should be avoided in RP affected patients. Multivariate and multivariable analysis confirmed the associations. Further investigations are needed to understand the mechanism(s) underlying these findings.