Raynaud's Phenomenon Research Articles

Association of Combined Autoreactivity to Sm/RNP Common Motif and U1 RNP With Mixed Connective Tissues Disease and Systemic Lupus Erythematosus.

This study aimed to evaluate the clinical features in patients with suspected connective tissue disease who tested positive for anti-Sm/RNP common motif antibody with or without associated anti-RNP antibody. The titers of anti-Sm/RNP and anti-RNP antibodies were measured by the multiplex solid-phase bioassays (Bio-Rad). Clinical manifestations were compared among the three subgroups (RNP only, Sm/RNP only, and double positive for RNP and Sm/RNP). Patients were further evaluated for the diagnosis of mixed connective tissue disease (MCTD) and/or systemic lupus erythematosus (SLE) using accepted classification criteria. A total of 133 patients were included in this study. The rates of inflammatory arthritis and Raynaud phenomenon were significantly higher in patients testing positive for both anti-RNP and anti-Sm/RNP antibodies compared to anti-RNP only or anti-Sm/RNP only (69.1% vs 28.8% vs 25.0%, P < 0.0001 for arthritis and 59.5% vs 23.3% vs 37.5%, P = 0.0005 for Raynaud phenomenon). Area under the curve (AUC) values were 0.68 (95% confidence interval [CI] 0.59-0.77, P < 0.0001) for anti-Sm/RNP titers and 0.65 (95% CI 0.55-0.74, P = 0.0039) for anti-RNP titers with inflammatory arthritis. AUC values were 0.67 (95% CI 0.58-0.77, P = 0.0002) for anti-Sm/RNP titers and 0.59 (95% CI 0.49-0.69, P = 0.0352) for anti-RNP titers with Raynaud phenomenon. The odds ratios for the diagnosis of MCTD and SLE were significantly higher in patients with double positivity compared to those testing solely positive for anti-RNP antibody. Anti-Sm/RNP common motif autoreactivity when combined with anti-RNP antibody positivity identifies those patients who are closely related with certain clinical manifestations and who are associated with well-defined connective tissue disease such as MCTD or SLE.

Clinical Characteristics of Distinct Subgroups of Patients with Primary Sjögren's Syndrome Classified by Serological Profiles: A Comparison Study.

Sjögren's syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. The patients were categorized into three subgroups based on serological tests. These were (1) quadruple seropositivity (positive for anti-Sjögren's syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren's syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA); (2) double seropositivity (positive for ANA and anti-SSA/Ro antibodies); and (3) quadruple seronegativity (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple-seropositive patients was 72 (18.6%), double-seropositive 174 (43.2%), and quadruple-seronegative was 85 (21.1%). The age at diagnosis of quadruple-seropositive pSS was 42.4 ± 10.8, which was significantly younger than that of patients with double-seropositive and quadruple-seronegative pSS (p = 0.021, p = 0.112). In terms of organ involvement, salivary gland enlargement, arthralgia, arthritis, Raynaud's phenomenon, lymphadenopathy, cutaneous vasculitis, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinemia, and hypocomplementemia were more common in quadruple-seropositive patients with pSS than in quadruple-seronegative patients (p < 0.0001). The results of this study confirmed the strong impact of immunological markers on the pSS phenotype at the time of diagnosis. Immunological patterns play a central role in the phenotypic expression of the disease, even during the initial diagnostic phase, and can guide physicians in designing personalized treatment plans for patients with pSS.

Botulinum toxin for Raynaud's phenomenon: A decade of real-world evidence

Botulinum toxin for Raynaud's phenomenon: A decade of real-world evidence

Connective Tissue and Autoimmune Diseases Associated With Postsurgical Breast Augmentation: An Updated Review.

This review provides an updated overview of the association between breast augmentation and connective tissue diseases (CTDs). A narrative review of recent literature was conducted. Various autoimmune disorders, such as Raynaud's syndrome, rheumatoid arthritis (RA), and Sjögren's syndrome, have been reported in association with breast implants, particularly silicone implants. Symptoms can be diverse and systemic, including fatigue, joint stiffness, muscle pain, skin rashes, and neurological and gastrointestinal issues. Explantation has shown promise in alleviating symptoms, but the exact pathogenesis remains unclear. Recent studies emphasize the need for informed consent, vigilant monitoring, and multidisciplinary management. The association between breast implants and CTDs remains contentious. While advancements in implant technology have improved patient outcomes, concerns about long-term health implications persist. Continuous research is necessary to elucidate the mechanisms underlying these potential risks and to develop informed patient care guidelines. In this narrative review, we discuss the history of breast implants, illness associated with breast augmentation, and treatment of CTDs and autoimmune diseases associated with breast augmentation.

The association of outdoor temperature and self-reported Raynaud's phenomenon severity among people with systemic sclerosis: a Scleroderma Patient-centered Intervention Network Cohort study

Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum. People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0-10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation. Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6-8·1), which occurred at -25°C. Severity scores decreased minimally from -15°C to 5°C (0·05-0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37-0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5-2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0-4·1) at 35°C and 5·6 points (4·5-6·8) at 40°C. Results were similar for feels like temperature. Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns. Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University.

Outdoor temperatures and Raynaud's phenomenon in patients with systemic sclerosis

Outdoor temperatures and Raynaud's phenomenon in patients with systemic sclerosis

Interstitial Lung Disease Phenotypes and Predictive Risk Factors in Primary Sjögren's Syndrome.

Background/Objectives: The prevalence of Interstitial Lung Disease (ILD) and risk factors for its development in patients with primary Sjögren's syndrome (pSS) are still debated, possibly due to the existence of heterogeneous pSS-related ILD phenotypes. The aims of this study were: 1. To investigate the prevalence and predictive factors for ILD development in a single-center pSS cohort; 2. To characterize different pSS-ILD phenotypes. Methods: Clinical, laboratory and imaging data of pSS patients attending our center from January 2019 to September 2023 were retrospectively analyzed. ILD presence was confirmed on HRCT. Results: Forty-three out of 474 enrolled pSS patients presented ILD (M:F = 6:37), accounting for an overall ILD prevalence of 9.1%. In 19 cases, ILD was the first manifestation of pSS (ILD-onset), while in 24 ILD was diagnosed after pSS (ILD-incident). Compared to ILD-onset, ILD-incident patients more often presented pSS-related hematologic abnormalities (p = 0.012), cutaneous involvement (p = 0.027), inflammatory arthralgias (p = 0.026), C4 hypocomplementemia (p = 0.012) and positive RF (p = 0.031). On the other hand, ILD-onset patients were significantly older at pSS diagnosis (p = 0.008) and presented more severe fibrosis on HRCT (p = 0.008). On the univariate analysis, higher ESSDAI (p = 0.011), Raynaud's phenomenon (p = 0.009), anti-Ro52 (p = 0.031), hypergammaglobulinemia (p = 0.011), Rheumatoid Factor (RF) (p = 0.038) and C4 hypocomplementemia (p = 0.044) at baseline were associated to ILD development during follow-up. On the multivariate analysis, the ESSDAI at baseline (p = 0.05) and Raynaud's phenomenon (p = 0.013) at baseline were the only independent predictors of ILD development. Conclusions: ILD is a relatively common and clinically heterogenous pSS manifestation. Elevated disease activity at pSS onset is a risk factor for ILD development, prompting careful follow-up and intriguingly suggesting that immunomodulatory therapies may prevent ILD.

Extent of macroscopic vascular invasion predicts distant metastasis in primary leiomyosarcoma of the inferior vena cava.

In retroperitoneal leiomyosarcoma (RP LMS), the predominant issue is distant metastasis (DM). We sought to determine variables associated with this outcome and disease-specific death (DSD). Data were retrospectively collected on patients with primary RP LMS treated at a high-volume center from 2002 to 2023. For inferior vena cava (IVC)-origin tumors, the extent of macroscopic vascular invasion was re-assessed on each resection specimen and correlated with preoperative cross-sectional imaging. Crude cumulative incidences were estimated for DM and DSD and univariable and multivariable models were performed. Among 157 study patients, median tumor size was 11.0 cm and 96.2% of cases were intermediate or high grade. All patients underwent complete resection, 56.7% received chemotherapy (43.9% neoadjuvant) and 14.6% received radiation therapy. Only tumor size and grade and not site of tumor origin (e.g., IVC vs. other) were associated with DM and DSD (p < 0.05). Among 64 patients with IVC-origin tumors, a novel 3-tier classification was devised based on the level of intimal disruption, which was associated with both DM (p = 0.007) and DSD (0.002). In primary RP LMS, only tumor size and grade are predictive of DM and DSD. In IVC-origin tumors, the extent of macroscopic vascular invasion is also strongly predictive of these outcomes.

Cutaneous presentations of systemic sclerosis in skin of colour: A systematic review

AbstractSystemic sclerosis (SSc), a rheumatologic autoimmune disease, can present diversely, especially in patients with skin of colour (SOC). Differences in clinical manifestations among SOC individuals compared to predominantly White populations require a comprehensive examination to optimize diagnosis and treatment. This systematic review aims to explore the differences in SSc manifestations among individuals with SOC, identifying variations in disease severity, clinical features and psychosocial impacts. A systematic review of the literature was conducted following PRISMA guidelines. Databases searched included PubMed, SCOPUS, Cochrane and Web of Science, focusing on studies published within the last 10 years. Nine studies were selected and qualitatively analysed due to the heterogeneity of study types. Key findings highlight significant variations in disease severity and cutaneous clinical features among SOC cohorts compared to predominantly White populations. Raynaud's phenomenon was prevalent across all ethnicities; however, SOC groups exhibited fewer hallmark features of scleroderma, such as telangiectasias, calcinosis and digital swelling, which complicates diagnosis. SOC individuals showed a higher propensity for severe pulmonary complications and increased mortality rates. Atypical cutaneous presentations in SOC were associated with disease progression. Psychosocial impacts were more pronounced in SOC individuals, with greater awareness and dissatisfaction over cutaneous symptoms. Recognizing the atypical presentations of SSc in SOC is critical for early diagnosis and optimizing patient outcomes. The study underscores the need for further research to determine if observed differences are due to variations in prevalence, genetic factors or insufficient training in recognizing cutaneous manifestations in SOC. Enhanced awareness and targeted training for healthcare providers are essential to address these diagnostic challenges and improve care for SOC patients with SSc.

Genetic and functional analysis of Raynaud’s syndrome implicates loci in vasculature and immunity

Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative trait loci (eQTLs), particularly in distal arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci modified gene expression and in situ RNAscope clarified the specificity of ADRA2A in small vessels and IRX1 around small capillaries in the skin. A functional contraction assay in the cold showed lower contraction in ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth muscle cells. Overall, our study highlights the power of genome-wide association testing with functional follow-up as a method to understand complex diseases. The results indicate temperature-dependent adrenergic signaling through ADRA2A, effects at the microvasculature by IRX1, endothelial signaling by NOS3, and immune mechanisms by the HLA locus in Raynaud's syndrome.

Isolation, Identification, and Characterization of Forced Degradation Products of Bosentan by Using Advanced Analytical Techniques

ABSTRACTThe present study explains the degradation behavior of bosentan (BOS), active pharmaceutical ingredient (API) (BOS monohydrate), a Food and Drug Administration (FDA)–approved drug used for the treatment of chronic heart failure, subarachnoid hemorrhage, and Raynaud's syndrome pulmonary hypertension. The stress study was performed under various stress conditions such as acid hydrolysis, base hydrolysis, oxidation, thermal degradation, and photolysis as per International Council for Harmonization (ICH) guidelines and found three degradation products (DPs) under acid hydrolysis conditions (1 N HCl/4 h/60°C reflux conditions) (the net degradation of API ∼ 21.39%). The drug was found to be stable under the remaining conditions (thermal, photolytic, oxidative, and basic hydrolytic conditions). Mechanisms for forming the three acid DPs were also proposed and discussed. The DPs were initially detected by ultrahigh‐performance liquid chromatography–mass spectrometry analysis. These DPs were isolated by preparative HPLC and then characterized by high‐resolution mass spectrometry and nuclear magnetic resonance spectroscopy techniques. Based on the structural characterization study, all these DPs are new and not reported elsewhere in the literature to my knowledge. Many reports were found in the literature for the quantification of the drug in the APIs and formulation products. However, there is no report published yet for the identification and characterization of DPs of the BOS drug.

Serum levels of biomarkers related to severity staging of Raynaud’s phenomenon, neurosensory manifestations, and vibration exposure in patients with hand-arm vibration injury

Our aim was to explore possible relationships between serum levels of biomarkers in patients with hand-arm vibration injury in relation to the severity of the vascular, i.e., Raynaud’s phenomenon (RP), and neurosensory manifestations, the current exposure level, and the duration of exposure. This study was of case series design and involved 92 patients diagnosed with hand-arm vibration injury. Jonckheere’s trend test was used to assess any association between serum levels of biomarkers and RP as well as neurosensory manifestations, graded by the International Consensus Criteria. Generalized linear models with adjustment for possible confounders were also used for associations between serum levels of biomarkers and; (1) severity of RP recorded as the extent of finger blanching calculated with Griffin score, (2) vibration perception thresholds, (3) magnitude of current exposure as [A(8); (m/s2)] value, and (4) the duration of exposure in years. Serum levels of thrombomodulin, von Willebrand factor, calcitonin gene related peptide (CGRP), heat shock protein 27, and caspase-3 were positively associated with severity of RP. Serum levels of CGRP were positively associated with the neurosensory component. No associations with exposure were shown for these biomarkers. For Intercellular adhesion molecule 1 and monocyte chemoattractant protein 1, no associations were found with neither severity nor exposure. Levels of serum biomarkers associated with endothelial injury or dysfunction, inflammation, vasodilation, neuroprotection, and apoptosis were positively associated with the severity of hand-arm vibration injury.

Delayed diagnosis of TAFRO syndrome: A case report.

TAFRO syndrome is a systemic inflammatory disorder, manifesting as thrombocytopenia (t), anasarca (a), fever (f), reticulin myelofibrosis/renal insufficiency (r), and organomegaly (o), and considered as a unique clinical subtype of idiopathic multicentric Castleman disease (iMCD). Such syndrome gave rise to a clinical picture similar to that of either a connective tissue disease or an autoimmune disease. A Chinese young female initially presenting with arthralgia, Raynaud phenomenon, generalized edema, and a positive anti-small nuclear ribonucleoprotein particle antibody was diagnosed as mixed connective tissue disease. The kidney biopsy showed thrombotic microangiopathy. Bone marrow smear showed bone marrow hyperplasia and biopsy revealed suspected light chain restricted expression, megakaryocyte proliferation, and moderate to severe bone marrow fibrosis. A lymph node biopsy was conducted and the histopathological findings were consistent with the subtype of mixed Castleman disease. The clinical symptoms were relieved after regular chemotherapy. After above examination results and clinical manifestations, the final diagnoses was TAFRO syndrome. The she was started on chemotherapy with bortezomib, cyclophosphamide, and dexamethasone. After chemotherapy, symptoms such as thrombocytopenia, hematuria and proteinuria disappeared, lymphadenopathy and VEGF level decreased, and bone marrow fibrosis relieved. Our case illustrated the first cases of shared characteristics of mixed connective tissue disease and iMCD-TAFRO syndrome. Cytokines may play a role in the shared pathogenicity of the iMCD-TAFRO syndrome and systemic autoimmune diseases. Therapy directly against inflammatory factors such as corticosteroids or chemotherapy have an important therapeutic implication.

Comparison of serum exosome miRNA from patients with Raynaud's phenomenon with positive and negative serum antinuclear antibodies.

To compare the microRNAs (miRNAs) contained within serum exosomes isolated from patients with Raynaud's phenomenon (RP) and negative antinuclear antibodies (ANA) to the miRNA contained in serum exosomes isolated from patients with RP and positive ANA. Serum exosomes were isolated employing a polymer precipitation procedure. Next Generation Sequencing (NGS) was used to identify the miRNAs contained in the exosomes isolated from the two clinical cohorts and to analyse the differences in their contents. The NGS results identified six miRNAs that displayed significant differences in their content between serum exosomes from patients with RP with negative serum ANA compared to miRNAs contained in serum exosomes from patients with ANA-positive RP. A comparative analysis of miRNAs contained within serum exosomes of patients with RP and negative ANA vs. samples from patients with RP and positive ANA identified several differentially expressed miRNAs that may represent non-invasive biomarkers to assist in the identification of patients with RP at risk of evolving into systemic sclerosis.

Coexistence of anti-KS and anti-TIF1-γ antibodies in clinically amyopathic dermatomyositis presenting with rapid progression of interstitial lung disease.

Polymyositis/Dermatomyositis (PM/DM) is an idiopathic inflammatory myopathy (IIM) manifesting mainly as symmetrical proximal muscle weakness and/or typical cutaneous features due to autoimmune mechanisms. Clinically amyopathic dermatomyositis (CADM) is a subset of DM that exhibits only the typical cutaneous features without any clinical muscle symptoms. Several autoantibodies have been found specifically in patients with PM/DM, including CADM patients. Anti-KS antibody is one of a group of anti-aminoacyl transfer RNA (ARS) antibodies that are mainly associated with fever, Raynaud's phenomenon, polyarthritis, and interstitial lung disease (ILD), whereas anti-TIF1-γantibody is frequently found in DM patients with malignancy. Here, we report a CADM patient having both anti-KS antibody and anti-TIF1-γantibody. This patient developed an acute exacerbation of ILD and was successfully treated with high dose corticosteroid pulse therapy together with immunosuppressive agents. Although earlier experience had indicated that the seminal characteristic of anti-KS-positive ILD was slowly developing disease onset with little or no progression over the clinical course, the present patient suffered rapidly progressive disease.

Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration's adverse event reporting system databases.

This study aimed to investigate the real-world profile of adverse events (AEs) associated with gepant medications in the clinical treatment of migraines by analyzing data collected from the VigiAccess database and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. As novel migraine therapies, gepants act by targeting the calcitonin gene-related peptide (CGRP) pathway, demonstrating effective control of migraine attacks and good tolerability. Nonetheless, comprehensive real-world studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research. Leveraging these two international adverse event reporting system databases, we systematically gathered and analyzed reports of AEs related to gepant medications, such as rimegepant. Our focus encompasses but is not limited to severe, new, and rare adverse reactions induced by the drugs, as well as safety issues pertaining to the gastrointestinal, cardiovascular, hepatic, and renal systems. Through descriptive statistical analyses, we assessed the incidence and characteristics of AEs, compared AEs among gepants, and uncovered previously unknown AE information, all with the goal of providing a reference for the selection of clinical treatment regimens and AE monitoring. By extracting all AE reports concerning "rimegepant", "atogepant", and "ubrogepant" from the VigiAccess and FAERS database since its establishment up to 31 March 2024, a retrospective quantitative analysis was conducted. The reporting odds ratio (ROR) method were used to compare AEs among the three gepants. In the VigiAccess and FAERS databases, 23542 AE reports in total, respectively, were identified as being related to gepant medications. Among gastrointestinal system AEs, rimegepant had the greatest proportion and greatest signal strength; nausea was most severe and had the strongest signal in rimegepant AEs, whereas constipation was most prominent and had the strongest signal in atogepant AEs. In skin and subcutaneous tissue disorders, rash and pruritus were more frequently observed with rimegepant, followed by ubrogepant. Alopecia emerged as a novel AE, being more severe in rimegepant and secondarily in atogepant. Regarding cardiac disorders, the three gepants showed comparable rates of cardiac AEs, yet rimegepant exhibited the strongest AE signal. In musculoskeletal and connective tissue AEs, ubrogepant presented the most positive signals for skeletal muscle AEs. Furthermore, among the rare blood and lymphatic system disorder AEs, rimegepant had the highest number of reports of Raynaud's phenomenon and the strongest signal. The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets. Gepant medications exhibit similarities and differences in their safety profiles. Analysis of the two databases indicated the presence of AEs across various systems, including gastrointestinal disorders, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue disorders, organ-specific effects, and liver diseases. However, each drug displays distinct incidences and signal intensities for these AEs. Additionally, the study revealed a rare AE in the form of Raynaud's phenomenon. These findings suggest that during clinical use, individualized medication selection and AE monitoring should be based on the patient's physiological condition and specific characteristics.

A case of Buerger's disease with vasculopathy and skin fibrosis requiring differential diagnosis from systemic sclerosis.

Buerger's disease is characterized by peripheral ischemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis. The patient exhibited Raynaud's phenomenon in year X-3, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year X. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis, several findings in this case were atypical for systemic sclerosis, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation.

Raynaud's Phenomenon: A Current Update on Pathogenesis, Diagnostic Workup, and Treatment.

Raynaud's phenomenon (RP) is a condition characterized by episodic, excessive vasoconstriction in the fingers and toes, triggered by cold or stress. This leads to a distinctive sequence of color changes in the digits. Pallor indicates reduced blood flow due to oxygen deprivation, while erythema appears as reperfusion. RP can be primary, with no identifiable underlying cause, or secondary, associated with other conditions. These conditions include autoimmune diseases, most commonly systemic sclerosis, vascular diseases; and neurological conditions. While the exact cause of RP remains unclear, genetic and hormonal (estrogen) factors are likely contributors. The pathogenesis of RP involves a complex interaction between the vascular wall, nerves, hormones, and humoral factors, disrupting the balance between vasoconstriction and vasodilation. In primary RP, the vascular abnormalities are primarily functional. However, in secondary RP, both functional and structural components occur in blood vessels. This explains why digital tissue damage frequently occurs in secondary RP but not primary RP. Diagnosis of RP is primarily clinical. Recent advancements in imaging techniques have aided in diagnosis and monitoring, but nail fold capillaroscopy remains the gold standard for distinguishing between primary and secondary RP. If there are signs of acute ischemic injury, vascular imaging, particularly preoperatively, is crucial to rule out other vaso-occlusive conditions. Management of RP focuses on alleviating symptoms and preventing tissue damage. Vasodilator medications are the first-line treatment when general measures like warmth and stress management are not sufficient. Dihydropyridine calcium channel blockers (CCBs), such as nifedipine, are commonly used for vasodilation. Phosphodiesterase-5 inhibitors and prostaglandin analogs are alternative options for patients who do not respond to CCBs or have ischemic tissue damage. Bosentan, an endothelin-1 receptor antagonist, has shown effectiveness in treating and preventing digital ulcers, especially in patients with multiple ulcers. For severe cases, botulinum toxin injections or sympathectomy surgery can be used to control RP symptoms. However, botulinum toxin injections require repeated administration, and sympathectomy's long-term effectiveness is uncertain. Fat grafting is a promising surgical therapy for promoting healing and preventing tissue injury.

Clinically relevant differences between primary Raynaud's phenomenon and secondary to connective tissue disease

ObjectivesRaynaud's phenomenon (RP) is a symptom complex associated with digital vascular compromise. Our aim was to examine for clinically relevant differences between primary RP (PRP) and secondary RP (SRP) to connective tissue disease. MethodsWe report cross-sectional results from the Patient Survey of experiences of Raynaud's Phenomenon (PASRAP), which aimed to explore the broad-ranging impact of RP. The survey was widely distributed online including via social medial. Participation was voluntary and responses were anonymous. Results1229 respondents completed PASRAP with self-reported RP: PRP 218 (17.7 %) and SRP 1011 (82.3 %) of which 903 (92.9 %) Systemic Sclerosis. The mean (SD) age was significantly lower in respondents with PRP (41.7 [11.8] vs 54.2 [12.4] years, P<0.0001). During attacks, more subjects with SRP reported cyanotic colour changes (92.2 % vs 86.5 %, P=0.0089). Patients with PRP experienced more pain (72.1 % vs 55.9 %, P<0.0001), numbness (80.3 % vs 69.4 %, P=0.0016), stinging/throbbing (93.4 % vs 80.8 %, P<0.0001), and tingling (84.0 % vs 77.5 %, P=0.0345). Only half of respondents’ symptoms were adequately controlled by their current medication(s), more commonly in SRP (55.2 % vs 45.2 %, P=0.0084). There were important differences in the triggers, number, and seasonal variation of RP attacks. ConclusionThere are clinically relevant differences between PRP and SRP concerning the multifaceted lived patient experience of RP. Neurosensory symptoms are more common in PRP. Patients with SRP are older and present with more colour changes, overrepresented by cyanosis, and with less complete resolution of symptoms between attacks. These data provide novel insights for future RP clinical trial design.

An inexpensive and effective device to manage nasal Raynaud's and rosacea overlap symptoms.

Raynaud’s phenomenon (RP) commonly leads to reduced circulation to digits, ears or nose. Nasal RP is a difficult condition to manage with medical treatments. This correspondence explored 2 cases of nasal RP being managed by a novel nasal warming device.