Raynaud's phenomenon associated with psoriatic arthritis.

We report a case of Raynaud's phenomenon in a patient with psoriatic arthritis (PsA). A middle-aged right-handed housewife presented with complaints of severely painful hand discolouration for 1 week, which usually worsened with cold exposure. She was diagnosed with PsA 6 months earlier. Her PsA was well controlled with weekly methotrexate. Physical examination showed no features of scleroderma or skin necrosis of her right hand. Both radial pulses were strong and symmetrical. Her nailfolds were visibly normal. The extractable nuclear antigen panel and other blood investigations were negative for scleroderma and other possible causes of secondary Raynaud's phenomenon. Occupational or environmental factors were also excluded. Dermatoscope examination of the nailfolds revealed some areas of dilated capillary loops, areas of vascular sparing and proximal nail fold telangiectasia. The diagnosis of secondary Raynaud's phenomenon was made, and an oral calcium channel blocker was started. The patient had significant improvement in symptoms shortly afterwards.

COVID-19 associated with Raynaud's phenomenon in a vibration-exposed worker.

This is the first known case report of COVID-19-related Raynaud's phenomenon (RP) identified at routine health surveillance of a male exposed to hand-transmitted vibration. The temporal relationship with COVID infection followed the course previously reported, being a late feature associated with mild COVID, and followed by gradual spontaneous recovery. It is not known whether the RP, in this case, is solely due to COVID or represents a summative effect of COVID and vibration exposure. A prudent approach is recommended in such circumstances with limitation of vibration exposure and continuing frequent surveillance pending improvement of the RP, with further prompt investigation if the expected recovery does not occur.

Risk factors of systemic lupus erythematosus patients with pulmonary arterial hypertension: A systematic review and meta-analysis.

BACKGROUND: To investigate the risk factors for the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE). METHODS: The literature related to risk factors for the development of PAH in SLE patients was searched by the computer on China national knowledge infrastructure (CNKI), PubMed, and Embase, and the literature search was limited to the period of library construction to October 2022. Two researchers independently performed literature screening and literature information extracting, including first author, publication time, case collection time, sample size, and study factors, and used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the literature. The relationship between each clinical manifestation and laboratory index and the occurrence of PAH in SLE patients was evaluated based on the ratio (OR value) and its 95% CI. RESULTS: A total of 24 publications were included, including 23 case-control studies and 1 cohort study with NOS ≥ 6, and the overall quality of the literature was high. The risk of PAH was higher in SLE patients who developed Raynaud phenomenon than in those who did not [OR = 2.39, 95% CI (1.91, 2.99), P < .05]; the risk of PAH was higher in SLE patients who were positive for anti-RNP antibodies than in those who were negative for anti-RNP antibodies [OR = 1.77, 95% CI (1.17, 3.2.65), P < .05]; the risk of PAH was higher in SLE patients with interstitial lung lesions than in those without combined interstitial lung lesions [OR = 3.28, 95% CI (2.37, 4.53), P < .05]; the risk of PAH was higher in SLE patients with combined serositis than in those without serositis [OR = 2.28, 95% CI (1.83, 2.84), P < .05]. The risk of PAH was higher in SLE patients with combined pericardial effusion than in those without pericardial effusion [OR = 2.97, 95% CI (2.37, 3.72), P < .05]; the risk of PAH was higher in SLE patients with combined vasculitis than in those without vasculitis [OR = 1.50, 95% CI (1.08, 2.07), P < .05]; rheumatoid factor-positive SLE patients had a higher risk of PAH than those with rheumatoid factor-negative [OR = 1.66, 95% CI (1.24, 2.24), P < .05]. CONCLUSION: Raynaud phenomenon, vasculitis, anti-RNP antibodies, serositis, interstitial lung lesions, rheumatoid factor, and pericardial effusion are risk factors for the development of PAH in patients with SLE.

Kaposiform hemangioendothelioma presented with raynaud phenomenon: a case report.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm affecting infants or young children. KHE includes a spectrum of lesions, ranging from small and superficial tumors to large and invasive lesions with Kasabach-Merritt phenomenon (KMP). Currently, no published studies have reported a KHE presenting as thrombocytopenia and Raynaud phenomenon. CASE PRESENTATION: A 2-year-old boy with right hand swelling and thrombocytopenia was admitted to our hospital. His right hand turned swelling and red, even occasionally cyanotic. This condition became worse in response to cool environments and improved with warming, and platelet counts were between 50 ~ 80 × 10^9/L. Physical examination on admission revealed the swelling and frostbite-like rash of the right-hand fingers, and the skin temperature of the right hand was lower than the left. On day 3 of admission, chest CT results showed an irregular mass on the right side of the spine. The puncture biopsy demonstrated positive CD31, D2-40, and FLI1 immunohistochemical staining, but negative GLUT1 staining, confirming the diagnosis of KHE. Furthermore, endothelin-1 (ET1) expression levels significantly increased, and eNOS and A20 expression levels significantly decreased comparing with control patients. The patient received methylprednisolone and sirolimus treatments, and his condition gradually improved during the follow-up. CONCLUSIONS: We reported the first case of KHE presenting with thrombocytopenia and Raynaud phenomenon. The development of Raynaud phenomenon could be associated with increased ET-1 and reduced eNOS and A20 expressions. Careful differential diagnosis of hidden KHE should be considered in children with thrombocytopenia and Raynaud phenomenon.

ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10-8). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10-27) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 × 10-13) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (rG = -0.21; p-value = 2.3 × 10-3), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α2A-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.

Efficacy analysis of minimally invasive surgery for Raynaud's syndrome.

BACKGROUND: Raynaud's syndrome (RS), also referred to as Raynaud's phenomenon, is a vasospastic disorder causing episodic color changes in extremities upon exposure to cold or stress. These manifestations, either primary Raynaud's phenomenon (PRP) or associated with connective tissue diseases like systemic sclerosis (SSc) as secondary Raynaud's phenomenon (SRP), affect the quality of life. Current treatments range from calcium channel blockers to innovative surgical interventions, with evolving efficacy and safety profiles. METHODS: In this retrospective study, patients diagnosed with RS were selected based on complete medical records, ensuring homogeneity between groups. Surgeries involved microscopic excision of sympathetic nerve fibers and stripping of the digital artery's adventitia. Postoperative care included antibiotics, analgesia, oral nifedipine, and heat therapies. Evaluation metrics such as the VAS pain score and RCS score were collected bi-weekly. Data analysis was conducted using SPSS 26.0, with significance set at p < 0.05. RESULTS: In total, 15 patients formed the experimental group, with five presenting fingertip soft tissue necrosis and ten showing RS symptoms. Comparative analysis of demographic data between experimental and control groups, both containing 15 participants, demonstrated no significant age and gender difference. However, the "Mean Duration of RP attack" in the experimental group was notably shorter (9.47 min ± 0.31) than the control group (19.33 min ± 1.79). The RS Severity Score also indicated milder severity for the experimental cohort (score: 8.55) compared to the control (score: 11.23). Postoperative assessments at 2, 4, and 6 weeks revealed improved VAS pain scores, RCS scores, and other measures for the experimental group, showing significant differences (p < 0.05). One distinctive case showcased a variation in the common digital nerve and artery course in an RS patient. CONCLUSION: Our retrospective analysis on RS patients indicates that microsurgical techniques are safe and effective in the short term. As surgical practices lean towards minimally invasive methods, our data supports this shift. However, extensive, prospective studies are essential for conclusive insights.

Domain reporting in systemic sclerosis-related Raynaud's phenomenon: An OMERACT scoping review.

BACKGROUND: Raynaud's phenomenon (RP) is a cardinal feature of SSc and is associated with significant disease-related morbidity that impacts on quality of life. The assessment of SSc-RP is challenging. The aim of this scoping review was to evaluate the outcome domains studied and outcome measures used in clinical studies of SSc-RP. METHODS: Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were used to identify randomized control trials (RCTs), quasi-randomized studies, case-control studies, prospective and retrospective cohort studies, case series, and cross-sectional studies of adult participants with SSc-associated RP, written in English. A minimum of 25 participants for studies of imaging modalities and 40 participants for questionnaire-based studies was required for inclusion. Basic laboratory and genetic studies were excluded. No limitations were imposed based on intervention, comparator, or study setting. Study characteristics and primary and secondary target domains in each study were recorded. RESULTS: 58 studies (24 randomized clinical trials) were included in the final analysis. The commonest domains captured were severity of attacks (n=35), frequency of attacks (n=28), and duration of attacks (n=19). Objective assessments of digital perfusion were also commonly used in studies of SSc-RP. CONCLUSION: The outcome domains and the associated outcomes used to assess the impact of SSc-RP in research studies are broad and have varied across studies. The results of this study will inform the OMERACT Vascular Disease in Systemic Sclerosis Working Group to establish a core set of disease domains encompassing the impact of RP in SSc.

Diagnostic accuracy and predictive value of autoantibody profiles in patients with systemic sclerosis: a single-center study.

OBJECTIVE: To determine diagnostic accuracy and evaluate the predictive value of autoantibody profiles in patients with systemic sclerosis (SSc). METHODS: A total of 140 patients with SSc (125 female, mean age 54.2 ± 14.2 years) were analyzed by a multiplex line immunoassay (Euroimmun) for autoantibodies against 12 SSc-related antigens. Associations between the presence of the autoantibodies and demographic clinical manifestations of patients with SSc were investigated. RESULTS: The sensitivity and specificity of this assay were as follows: 32.9% and 99.4% for anti-Scl-70, 29.3% and 88.9% for anti-CENP A, 28.6% and 87.8% for anti-CENP B, 7.1% and 97.8% for anti-RP11, 5.7% and 100% for anti-RP155, 2.9% and 99.4% for anti-NOR 90, 2.9% and 98.9% for anti-Th/To, 1.4% and 96.7% for anti-PM-Scl-100, 5.0% and 98.3% for anti-PM-Scl-75, and 2.9% and 97.2% for anti-Ku, respectively. Anti-Scl-70 was significantly associated with sine scleroderma (P = 0.003), digital ulcers (P = 0.047), and Raynaud's phenomenon as the first clinical manifestation of onset (P = 0.017). SSc-ILD was more common in patients with anti-Scl-70 (P = 0.029) and less frequent in patients with anti-CENP A (P < 0.001) and anti-CENP B (P < 0.001). There was a significant association between PAH with anti-CENP A (P = 0.008) and anti-CENP B (P = 0.025). Renal involvement was significantly related to anti-NOR90 (P = 0.026) and anti-Th/To (P = 0.026). CONCLUSIONS: This study confirmed the important role of autoantibodies in accurately diagnosing SSc. The autoimmune profile of patients with SSc was related to specific disease manifestations. Key Points • Autoantibody profiles were useful for diagnosing SSc and predicting clinical features of patients.

The effect of silver fibre gloves on Raynaud's phenomenon in patients with systemic sclerosis: a double-blind randomized crossover trial.

OBJECTIVES: Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of RP in SSc patients. We aim to evaluate the clinical efficiency of this intervention. METHODS: A multicentre, double-blind, randomized trial was performed, accounting for interindividual differences and external factors using a crossover design. Patients were randomized in two groups: group 1 wore 8% silver fibre gloves in period 1 and normal gloves in period 2 and group 2 vice versa. Each period lasted 6 weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models. RESULTS: A total of 85 SSc patients were included, with 76 completing the study. The mean RCS during 2 weeks before the study (i.e. without gloves) was 6.4 (s.d. 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (s.d. 2.3) with a similar course over time. There was no difference in mean RCS over time between the type of gloves [ß = 0.067 (95% CI -0.006, 0.19)]. Of secondary outcomes, total SHAQ [ß = 0.036 (95% CI 0.026, 0.046)] was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves vs one patient with silver fibre gloves [odds ratio 3.2 (95% CI 0.32, 31.1)]. CONCLUSIONS: Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8% silver fibre gloves is associated with less disease burden as measured in this study by the RCS compared with normal gloves. CLINICAL TRIAL REGISTRATION NUMBER: Netherlands Trial register (https://www.trialregister.nl/) NL7904.

A phase 2 trial investigating the effects of the angiotensin II type 2 receptor agonist C21 in systemic sclerosis-related Raynaud's.

OBJECTIVE: Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP. METHODS: This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3-7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models. RESULTS: For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°C*s vs 19 558°C*s), but not significantly (P = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P = 0.036). C21 was well tolerated. CONCLUSION: Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04388176.

Anti-Phosphatidylethanolamine and Anti-Phosphatidylserine Antibodies-Association with Renal Involvement, Atherosclerosis, Cardiovascular Manifestations, Raynaud Phenomenon and Disease Activity in Polish Patients with Systemic Lupus Erythematosus.

OBJECTIVE: To evaluate the association between anti-phosphatidylethanolamine (aPE) and anti-phosphatidylserine (aPS) antibodies and cardiovascular risk, organ involvement and disease activity in systemic lupus erythematosus (SLE) patients. METHODS: We studied 93 SLE patients and 30 controls. We analyzed levels of anti-phospholipid antibodies, including aPS and aPE, the profiles of antinuclear, anti-neutrophil cytoplasmic (ANCA) and anti-endothelial antibodies, carotid intima-media thickness (cITM) and atherosclerotic plaque presence, ankle-brachial and high resistance indices, atherosclerotic risk factors, organ manifestations and treatment. RESULTS: Levels of aPS and aPE were significantly higher in SLE patients in comparison with the controls (p = 0.038 and p = 0.044, respectively). aPS was associated with the risk of Raynaud's phenomenon (p = 0.021) development. aPE increased the risk of renal involvement (p = 0.049), cerebral stroke (p = 0.050), high vlues of cIMT (p = 0.041) development as well as occurrence of selected serological markers associated with activity of the disease such as anti-double stranded DNA (p = 0.021). The long duration of regular smoking (p = 0.021) and the high number of cigarettes/day (p = 0.015) were significantly associated with the risk of aPE occurrence. CONCLUSIONS: Patients with aPS and aPE are at risk of vascular involvement. Especially the presence of aPE may significantly increase the risk of thrombotic complications development in SLE patients without classical serological markers of APS. Finally, aPE might be used as a marker of disease activity and risk of renal injury development in this patient group. The classical atherosclerotic markers including lipid indices play an important role in complex analysis of cardiovascular risk in lupus patients and enable to identify patients at the highest risk and implement effective preventive, diagnostic and therapeutic procedures.

Spinal cord stimulator for the treatment of ischemic pain-Burger's disease and Raynaud's disease: A report of two cases and literature review.

Ischemic pain is the main symptom of a group of diseases that result in inadequate blood flow to the extremities and ischemia. In this symptomatology, two major diseases are distinguished: Critical vascular disease and Raynaud's phenomenon. Critical vascular disease background of atherosclerosis caused by diabetes mellitus or hypertension. Raynaud phenomenon is divided into primary and secondary form. The primary form is due to vasospasm and there is no underlying cause. Secondary form is associated with underlying connective tissue or rheumatic diseases, peripheral vascular diseases such as thromboangitis obliterans (Burger's disease). Clinical findings in Raynaud's disease are vasomotor changes with cold exposure such as bruising, coldness, painful paresthesias, and ulcers due to chronic ischemia. Clinic presentation in critical ischemic disease is intermittent claudication for earlier stage and resting pain, gangrene, necrosis, and trophic changes were added in advanced stages. The treatment of the Raynaud 's disease in early stage is medical and conservative. In case of advanced stage ischemic vascular disease, medical treatment resistant pain, insufficient response to endovascular treatment, and inoperabl cases, interventions such as sympathectomy and spinal cord stimulation (SCS) can be applicable. SCS reduces vascular resistance through vasodilator mediators and increases blood flow. SCS also suppresses sympathetic vasoconstriction, increases tissue vascularity, reduces tissue damage, provides ulcer healing and pain reduction. In this report, we demonstrated that persistent Raynaud's disease and advanced stage Burger's disease were successfully treated with SCS.

Clinical Study on Systemic Lupus Erythematosus Complicated with Knee Bone Infarction.

Objective: The present study aims to (1) analyze the clinical characteristics and related influencing factors of knee bone infarction in systemic lupus erythematosus (SLE) and (2) improve the understanding of SLE complicated with knee bone infarction. Methods: The data of patients with SLE complicated with knee bone infarction were retrospectively analysed; patients with SLE during the same period who matched in age, gender, and disease duration were selected as control subjects, with a 1 : 1 ratio with the SLE group. The clinical data were collected to analyze the risk factors for SLE complicated with knee bone infarction. Results: In a total of 36 (6.4%) of 563 patients aged 19-33 (25.8 ± 4.8) years who had SLE during the same period, the disease was complicated with knee bone infarction. The diagnosis of knee bone infarction was made at an SLE duration of 7-65 (26.2 ± 15.7) months. During the SLE course, knee bone infarction occurred within 1 year in 6 cases (16.7%), within 1-5 years in 28 cases (77.8%), and in >5 years in 2 cases (5.6%). Raynaud's phenomenon incidence and anti-nRNP antibody positivity were significantly higher in the knee bone infarction group than in the control group (P < 0.01 and P < 0.05, respectively). The cumulative glucocorticoid dose at 1, 3, and 6 months was significantly higher in the knee bone infarction group than in the control group (P < 0.05). SLE complicated with knee necrosis had a statistically significant rank correlation with Raynaud's phenomenon (r = 0.445, P < 0.001), anti-nRNP antibody (r = 0.309, P=0.008), and renal injury (r = 0.252, P=0.032). The multivariate analysis of SLE complicated with knee bone infarction showed that Raynaud's phenomenon was an independent influencing factor for the complicated knee bone infarction in SLE patients (OR = 4.938, P=0.004), and the probability of SLE complicated with knee bone infarction in Raynaud's phenomenon positive patients was 4.938 times that of Raynaud's phenomenon negative patients. Conclusions: The risk of knee bone infarction was relatively high in patients with SLE within a 5-year disease course and in young patients. The risk factors were Raynaud's phenomenon, anti-nRNP antibody positivity, and early high-dose glucocorticoid therapy.

Erasmus Syndrome: A Case Report and Literature Review.

BACKGROUND Erasmus syndrome is a rare disease entity characterized by the development of systemic sclerosis (SSc) in a background of silica exposure or silicosis. CASE REPORT We report the case of a 40-year-old Filipino man who previously worked in a silica grind mill for 10 years and eventually developed Erasmus syndrome. The patient initially presented with chronic back pain in 2018 associated with findings of pulmonary tuberculosis on chest X-ray, with notable improvement after 6 months of anti-tuberculosis treatment. However, his back pain recurred in 2021; this time with arthralgia, Raynaud's phenomenon, thickening of both hands, skin hypopigmentation on the chest, back, and forehead, and exertional dyspnea. Physical examination revealed salt-and-pepper dermopathy and skin tightening over the back, chest, and extremities. Mobility of his hands was limited, associated with sclerodactyly and digital pitting. Antinuclear antibody-immunofluorescence and anti-scleroderma-70 antibodies were strongly positive, confirming the diagnosis of SSc. Chest computed tomography illustrated multiple subcentimeter nodules and enlarged mediastinal lymph nodes with eggshell calcifications, consistent with silicosis. Spirometry with body plethysmography was normal but diffusing capacity for carbon monoxide was severely reduced. Histopathology of the skin showed markedly thickened collagen bundles in the dermis. CONCLUSIONS Chronic silica exposure is a risk factor for the development of silicosis. The clinical course of patients with silicosis may be complicated by SSc. Maintaining a high index of suspicion is key to the diagnosis of Erasmus syndrome. The present report emphasizes the importance of preventive measures and surveillance among those with occupational exposure to silica. To our knowledge, this is the first documented case of Erasmus syndrome in the Philippines.