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Background: Cryoglobulinemia (CG) syndrome is a heterogeneous condition characterized by the presence of cryoglobulins in serum, often leading to vasculitis with protean clinical manifestations. Understanding the presentation of cryoglobulinemia-related symptoms based on cryoprecipitate levels, GC type, and severity at diagnosis is essential for effective management. Hence, this study aimed to provide a comprehensive analysis of patients with positive cryoglobulin detection to investigate these aspects. Methods: We conducted a retrospective review of clinical charts from patients with positive cryoglobulin detection at Colmar Hospital between May 2015 and April 2019. Results: Among 166 patients with positive cryoglobulins, the median cryoprecipitate value was 37 mg/L [IQR: 25–70], with 62% of patients below the 50 mg/L threshold. High cryoprecipitate levels were associated with C-virus hepatitis (p = 0.0007), increased fatigue (p = 0.001), fever (p = 0.0013), weight loss (p = 0.028), and musculoskeletal symptoms (p = 0.002). These patients also exhibited decreases in complement fractions (p-values 0.017 to 0.006). At the end of the one-year follow-up, they required frequent renal replacement therapy (p < 0.0001) and had a higher mortality rate (p = 0.02). Based on the CG type, patients with type I GC had splenomegaly (p = 0.039) and hemopathy (p = 0.001). According to severity at initial presentation, the severe patients had more purpura (p < 0.001), Raynaud's phenomenon (p = 0.039), and leukocytoclastic vasculitis on skin biopsy (p < 0.001), along with higher cryoprecipitate levels (p = 0.011). Multivariate analysis identified purpura (OR: 10.25), hematological malignancy (OR: 7.06), Raynaud's phenomenon (OR: 6.41), and cryoprecipitate levels (OR: 1.02) as significant markers of disease severity serving for the development of a severity score for clinical practice. Conclusions: This study identifies severity markers in patients with positive cryoprecipitate and proposes a score related to severity at diagnosis. [ABSTRACT FROM AUTHOR]

Background: Microvascular alteration in scleroderma patients is well documented. Microcirculatory changes can be visualized by nailfold capillary microscopy (NFC) examination which is a safe and noninvasive technique. This study aims to identify possible association between neutrophil-to-lymphocyte ratio (NLR) and microvascular changes detected by nailfold capillaroscopic examination in scleroderma patients. Results: The study was conducted on 25 patients with systemic sclerosis. On studying the correlation of NLR with laboratory parameters, we found significant positive correlations with erythrocyte sedimentation rate "ESR" and C-reactive protein "CRP" values (p = 0.000). Regarding the clinical manifestations, higher NLR was significantly related to the presence of digital ulcer (p = 0.023) and Raynaud's phenomenon (p = 0.015). There was significantly negative relation between NLR with cyclophosphamide treatment. Regarding NFC examination's results, there was significant negative correlation of NLR with capillary number/mm (p = 0.000) and significant positive correlation of NLR with capillary width (p = 0.005), and a significant relation of NLR with the presence of capillary hemorrhage and presence of active scleroderma pattern (p = 0.010) was also reported. Conclusion: High N/L ratio as a marker of inflammation was found to reflect severity of systemic sclerosis and is associated with larger capillary diameter and lower capillary number in nailfold capillaroscopy. Active scleroderma pattern was associated with high N/L ratio. Further longitudinal studies are needed to determine the frequency of nailfold videocapillaroscopy and N/L ratio. [ABSTRACT FROM AUTHOR]

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

Raynaud's phenomenon (RP) is a vasospastic disorder that affects the small blood vessels in the extremities such as the hands, feet, fingers or toes. It is a debilitating condition that can severely impact the patient's quality of life. Botulinum toxin (BTX) has been examined as a treatment option for RP, but its effect has been inconclusive. A systematic review has been conducted to determine the current evidence of BTX as a treatment for RP secondary to scleroderma. Major clinical databases Medline, Embase (via Ovid), the Cochrane Central Library, ClinicalTrials.gov, EU Clinical Trials Register and the ISRCTN registry were systematically searched from its inception to 27 November 2023 for studies describing BTX and RP. Standard mean differences of Quick-DASH scores, visual analogue scale pain (VAS-P) score and Raynaud's condition score (RCS) are reported with BTX treatment with a random-effect model. A total of 890 entries were retrieved. Of these, 19 met the inclusion criteria, and all studies were included for analysis. There was a significant effect (p = 0.03) with Quick-DASH score and VAS-P score (p < 0.00001) but a non-significant effect (p = 0.37) with RCS. BTX is a therapeutic option in the treatment of RP secondary to scleroderma; however, the evidence published so far is not sufficient to credit it as a revolutionary first line treatment. More research is needed to establish dosing, techniques and core outcome measures for BTX in RP. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis‐associated Raynaud phenomenon (SSc‐RP) confers poor outcomes, including ulceration, gangrene, autoamputation, and hand disability. Prostaglandin analogues (PG) are a group of prostacyclin‐derived drugs with properties that may address underlying complex mechanisms of SSc‐RP. This systematic review and meta‐analysis evaluated the efficacy and tolerability of PGs in SSc‐RP. Methods: We systematically reviewed randomized control trials (RCTs) evaluating PG use in SSc‐RP. The primary outcome was the severity of RP attacks. The secondary outcomes were the frequency and duration of RP attacks, healing of digital ulcers, development of new digital ulcers, change of capillary blood flow, patient health‐reported outcome measure (PROM‐VAS), and tolerability. Results: Eleven RCTs were included, reporting a total of n = 1081 individuals with SSc. PG confers a beneficial effect on RP severity in the short‐term, weighted Mean difference (WMD) −0.63 (95% CI −0.99, −0.27, I2 0%), with no difference in tolerability compared to placebo OR 1.88 (95% CI 1.00, 3.55, I2 = 1%). PG has nonsignificant trends towards improvement in RP frequency WMD of −0.32 (95% CI −0.76, 0.13, I2 = 0%), RP duration WMD −4.78 (95% CI −14.69, 5.14, I2 = 1%), PROM‐VAS WMD −4.81 (95% CI −11.31, 1.69, I2 = 67%), and new or recurrent digital ulcers OR 0.92 (95% CI 0.48, 1.76, I2 = 34%). Conclusion: PGs are beneficial in the short term to reduce the RP severity and are tolerable. Larger, adequately powered trials are needed for higher certainty evidence across SSc‐RP outcomes. [ABSTRACT FROM AUTHOR]

It is well established that host immunity plays a critical role in defending against colorectal cancer (CRC) progression. Connective tissue disease (CTD) encompasses a group of heterogeneous, immune-mediated disorders that present with diverse and often non-specific initial symptoms. Raynaud's phenomenon is a common feature, complicating early diagnosis. As CTD progresses, it can damage the skin, muscles, and blood vessels and may extend to the lungs, heart, kidneys, and other abdominal organs. Several studies have reported that CTD can lead to intestinal vascular occlusion and related inflammation, but the occurrence of related complications after intestinal surgery has been reported rarely. In this study, an elderly female patient with rectal cancer complicated with CTD was found to have unexplained proximal anastomotic stenosis during an attempt at fistula restoration 3 months after laparoscopy-assisted transanal total mesorectal excision (TaTME) and preventive terminal ileostomy, resulting in fistula failure. This case study aims to serve as a reference for clinicians in their future practice. [ABSTRACT FROM AUTHOR]

A 16‐year‐old male with hypermobility spectrum disorder (HSD) and Raynaud's phenomenon (RP) was referred to a clinical exercise physiologist (CEP) by their pediatric rheumatologist. The patient presented with arthralgia in the left knee and shoulder. Specifically, the left knee presented discomfort during activities of daily living (ADL), and the left shoulder had a reduced range of motion resulting from pain. Finally, complaints of painful fingers were also significant due to increased RP flare‐ups during winter. A posture analysis was conducted, indicating relatively poor posture. Range of motion and manual muscle testing were suboptimal in the shoulders, but optimal in the knees and hips. The Kendal test, patella compression test, and Clarke's sign were conducted due to knee pain. Functional tests included a pelvic bridge, squat, Neer's test, and wall push‐up. Finally, the modified pediatric clinical test of sensory interaction in balance (mPCTSIB) was completed to determine the interaction between balance systems. Analysis of all the tests conducted above confirmed the diagnosis of HSD and also indicated scapula dyskinesia, supraspinatus impingement, and patellofemoral pain syndrome. Consequently, the CEP treatment focused on strengthening the foot, knee, and hip kinetic chain, as a 12‐week home program, along with hand exercises as needed to aid in the pain and stiffness experienced during RP flare‐ups. The physiotherapist treatment was more hands on in the use of myofascial release, electrotherapy, taping, and posture correction of the neck and shoulder over four in‐house visits. Finally, a 6‐month follow‐up was conducted by the CEP, in which the patient showed improvement with a pain‐free range of motion and the ability to optimally conduct ADLs. [ABSTRACT FROM AUTHOR]

This case report describes a rare occurrence of a 25‐year‐old female diagnosed with both systemic sclerosis (SSc) and ankylosing spondylitis (AS), two distinct autoimmune diseases. The patient presented with a combination of symptoms, including progressive skin tightening, lumbosacral pain, and Raynaud's phenomenon, which complicated the diagnosis. Despite the challenges posed by the coexistence of SSc and AS, a multidisciplinary treatment approach involving corticosteroids, immunosuppressants, and supportive therapies led to significant clinical improvement. Over the course of 3 weeks, the patient's Rodnan Skin Score improved from 18 to 11, and her pain and overall disease activity were markedly reduced. Although skin sclerosis showed substantial improvement, pulmonary involvement remains a concern that requires long‐term monitoring. This case highlights the complexities in diagnosing and managing overlap syndromes, emphasizing the need for personalized treatment strategies and further investigation into the underlying genetic and immunological mechanisms. [ABSTRACT FROM AUTHOR]

"Erythromelalgia, also known as erythermalgia, is a rare vascular disorder characterized by intermittent redness, heat, and pain in the feet, hands, and sometimes the face. It can be primary with no clear cause or secondary due to underlying medical conditions. Lifestyle changes, such as avoiding triggers and maintaining an active lifestyle, can help manage symptoms, along with medications to control blood vessel dilation and nerve pain. Response to treatment varies widely, and comprehensive pain rehabilitation may be necessary in severe cases." [Extracted from the article]

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

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

Objectives EULAR supports the use of nailfold videocapillaroscopy (NVC) for identifying disease patterns (DPs) associated with SSc and RP. Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, for differentiating SSc patterns from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track–inspired algorithm for identifying DPs without the constraint of interobserver variability. Methods NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed upon (by ≥2 out of 3 interobservers) were subsequently analysed using in-house–developed software. The results for each variable were grouped according to the consensually agreed-upon DPs in order to identify useful hallmarks for categorizing them. Results A total of 851 NVCs (21 957 images) whose DPs had been consensually agreed upon were software-analysed. Appropriate cut-offs set for capillary density and percentage of abnormal and giant capillaries, tortuosities and haemorrhages allowed DP categorization and the development of the CAPI-score algorithm. This consisted of four rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus between the interobservers. Conclusion The CAPI-score algorithm may become a tool that is useful in assigning DPs by overcoming the limitations of subjectivity. [ABSTRACT FROM AUTHOR]

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Objective: Accumulating evidence suggests that differentially expressed circular RNAs (circRNAs) play critical roles in immune cells of systemic lupus erythematosus (SLE) patients. Hsa_circ_0000479 has been studied in the field of cancer and infection, whereas seldom studied in autoimmune diseases. The aim of this study was to investigate the role and clinical value of neutrophil hsa_ circ_0000479 in SLE. Methods: The expression levels of hsa_circ_0000479 in both healthy individuals and SLE patients' neutrophils were detected by qPCR and compared with those in peripheral blood mononuclear cells (PBMCs). In addition, the correlation of hsa_circ_0000479 levels in neutrophils with the clinical and immunological features of SLE patients was also analysed. Results: The expression levels of hsa_circ_0000479 in the patients with SLE were significantly higher in neutrophils than that of PBMCs, and also significantly higher than that in healthy controls (HCs). Moreover, the expression levels of hsa_circ_0000479 in neutrophils were negatively associated with absolute neutrophil count and complement 3 (C3), whereas positively correlated with anti-dsDNA and anti-nucleosome antibodies in SLE. In addition, SLE patients with higher levels of hsa_circ_0000479 demonstrated more several clinical manifestations, including Raynaud's phenomenon, alopecia and leucopenia. Conclusions: Hsa_circ_0000479 is up-regulated in neutrophils of SLE patients, and is also associated with several important laboratory indicators and clinical manifestations, suggesting that hsa_circ_0000479 in neutrophils was one of probable factors involved in the pathogenesis of SLE with potential clinical value. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Acromegaly is a chronic endocrine disease characterized by excessive secretion of growth hormone, which, in turn, leads to an increase in the secretion of insulin-like growth factor 1 in the liver. The targets for these hormones are most of the cells in our body. Excess growth hormone (in the vast majority of cases caused by hormone-producing pituitary adenoma – somatotropinoma), insulin-like growth factor leads to cellular, and tissue growth of almost all organs and systems, including the osteoarticular apparatus. Diagnosis of the disease in the early stages is often difficult and is established 5–10 years after the onset of symptoms, that leads to various complications and disability of patients. Often joint pain is the first manifestation of acromegaly. Damage to the musculoskeletal system causes a significant deterioration in the quality of life even when long-term stable remission of the underlying disease is achieved. In the article a clinical case with the peculiarities of diagnosing rheumatic disease in acromegaly is presented. A patient aged 56 years was diagnosed with acromegaly based on clinical and laboratory data, and a month later she underwent transnasal adenomectomy. However, Endocrinology Research Centre drew attention to the patient's complaints of pain in large joints, and therefore she was referred for a consultation to a rheumatologist at the Nasonova Research Institute of Rheumatology. As part of the examination, an increase in the titer of the antinuclear factor (1/2560) and the level of antibodies to ribonucleoprotein was revealed, which is most typical for mixed connective tissue disease. Treatment was prescribed and dynamic monitoring is being carried out.

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

Introduction: Raynaud's phenomenon (RP) is a quite common but often unrecognised vasospastic condition of the peripheral vessels. This may happen after exposure to the cold, stress, vibrations or a wide range of medical conditions. It causes episodic colour changes of the digits, firstly there is a pallor, followed by cyanosis and/or redness, usually with pain. Raynaud's phenomenon can be primary (i.e. Raynaud's disease) or secondary (i.e. Raynaud's syndrome) to underlying disease. Aim of the study: The aim of the study was to discuss the complex and incompletely understood pathophysiology of Raynaud's phenomenon and to evaluate treatment approaches of both 'uncomplicated' - mostly primary and 'complicated' - mostly secondary Raynaud's phenomenon. State of knowledge: Raynaud's phenomenon is a common disorder with an unclear pathophysiology. Although many treatment approaches have been reported, there is still no cure or gold standard therapy. Further investigations into treatment are required. Conclusions: Future research is needed to understand the complex pathogenesis of RP and to develop optimised approaches to management. [ABSTRACT FROM AUTHOR]

Purpose: To report two cases of non-granulomatous unilateral anterior uveitis in two female patients associated with autoimmune liver diseases (ALD), emphasizing the possibility of this rare coexistence as a polyautoimmunity phenomenon. Case descriptions: Case 1: An 18-year-old female with a history of congenital renal hypoplasia and metabolic syndrome presented with anterior uveitis in OS and a history of jaundice, blood elevated hepatic enzymes, and cholangioresonance compatible with primary sclerosing cholangitis (PSC). Laboratory work-up for additional autoimmune and infective causes were within normal limits. Case 2: An 58-year-old female presented an episode of anterior uveitis in OD and a history of Sjögren syndrome diagnosed at the age of 53, primary biliary cholangitis (PBC), systemic sclerosis, Raynaud's phenomenon, bilateral sacroiliitis, and vitiligo, consistent with polyautoimmunity and multiple autoimmune syndrome. Conclusions: Uveitis rarely coexists with ALD. However, it is essential to recognize the possibility of polyautoimmunity in patients presenting with ophthalmic manifestations and a previous diagnosis of ALD, such as PSC or PBC. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a chronic multisystemic disease characterized by immunological activation, diffuse vasculopathy, and generalized fibrosis exhibiting a variety of symptoms. A recognized precursor of SSc is Raynaud's phenomenon, which is part of the very early disease of systemic sclerosis (VEDOSS) in combination with nailfold videocapillaroscopy (NVC) impairment. The pathophysiology of ocular involvement, alterations in internal organs, and body integumentary system involvement in SSc patients are complicated and poorly understood, with multiple mechanisms presumptively working together. The most prevalent ocular symptoms of SSc are abnormalities of the eyelids and conjunctiva as well as dry eye syndrome, due to fibroblasts' dysfunction and inflammation of the ocular surface. In particular, lagophthalmos, blepharophimosis limitation of eyelid motion, eyelid telangiectasia, and rigidity or tightening of the lids may affect up to two-third of the patients. In addition, reduction in central corneal thickness, iris defects and higher rates of glaucoma were reported. In the first reports based on retinography or fluorescein angiography, about 50% of SSc patients showed signs of vascular disease: peripheral artery occlusion, thinning of retinal pigment epithelium and choroidal capillaries, ischemic areas surrounded by intraretinal extravasation and microaneurysms, and peripheral capillary non-perfusion. Successively, thanks to the advent of optical coherence tomography angiography (OCTA), several studies highlighted significant impairment of either the choriocapillaris and retinal vascular plexuses, also correlating with NVC involvement and skin disease, even in VEDOSS disease. Given the sensitivity of this technique, ocular micro-vasculopathy may act as a tool for early SSc identification and discriminate between disease stages. [ABSTRACT FROM AUTHOR]

Scleroderma or systemic sclerosis (SSc)‐associated digital ischaemic complications, such as digital ulcers (SSc‐DUs), appear relatively early during the disease course and are a major burden with substantial deterioration of quality of life. Expert rheumatologist and wound specialists have defined a DU; however, international application of the definition is still disorganised. Appearance of SSc‐DUs is secondary to the onset of Raynaud's phenomenon and as a consequence, recommended first‐line of treatment mainly includes vasodilators; however, many DUs are refractory to this treatment. Despite important practical issues, such as a lack of well‐characterised SSc‐wound healing animal model, significant efforts are needed to mechanistically understand the pathogenesis of SSc‐DUs for developing clinically targetable disease modifying therapies. [ABSTRACT FROM AUTHOR]

La exposición a la gravedad artificial (GA), a través de la centrifugación humana, constituye la base del tratamiento denominado terapia gravitacional (TG), mediante el cual se produce un estímulo mecánico sobre la pared vascular induciendo la síntesis y liberación de prostaciclina. Se usa desde hace más de cuatro décadas en Uruguay en el tratamiento de enfermedades de base vascular. En la esclerosis sistémica (ES) ha demostrado gran beneficio y excelente perfil de seguridad. Sin embargo, existe un desconocimiento en la comunidad científica acerca de la TG y de sus resultados. Evaluar la eficacia de la TG en la afección cutánea y vascular, calidad de vida y capacidad funcional y su perfil de seguridad en pacientes con ES. Estudio descriptivo y retrospectivo de pacientes con ES asistidos en un centro de autoinmunidad de Montevideo, tratados con TG en los últimos 10 años. Se incluyeron 50 pacientes: 48 mujeres (96%) y 2 hombres (4%), con una edad media de 62 ± 12 años. El tiempo medio de evolución de la ES al momento de inclusión en el estudio y al iniciar la TG fue de 6,8 ± 3,2 años y de 2,8 ± 3,2 años, respectivamente. Post-TG se observó una mejoría significativa del puntaje modificado de Rodnan (mRSS) (pre-TG 19,2 ± 8,7 vs post-TG 5,4 ± 5,0, p < 0,05), que no se relacionó con el tiempo de evolución de la enfermedad al inicio de la TG, extensión cutánea o perfil inmunológico. El grado de mejoría post-TG se correlacionó con un mayor mRSS inicial (R = 0,84, p < 0,05). Se observó mejoría significativa del número de pacientes con puffy fingers (pre-TG 50% vs post-TG 20% pacientes, p < 0,05), pero no en telangiectasias, pitting scars o esclerodactilia. La gravedad del fenómeno de Raynaud disminuyó significativamente, pre-TG: grado 3-4, 43/48 (89,6%) pacientes vs post-TG: grado ≤ 2, 42/47 (89,4%) pacientes, p < 0,05, así como también el dolor vascular medido por EVA (escala 0-10) (pre-TG: 7,6 ± 2,2 vs post-TG: 1,4 ± 1,2, p < 0,05). También se registraron casos de curación de úlceras digitales. En cuanto a los resultados reportados por los pacientes, el 97% refirieron mejoría en calidad de vida y el 89,5% mejoría en capacidad para realizar actividades de la vida diaria. No se registraron efectos adversos significativos. La TG mejoró el compromiso cutáneo y vascular, la calidad de vida y la capacidad funcional en pacientes con ES con excelente perfil de seguridad. Se necesitan ensayos clínicos controlados y aleatorizados para corroborar estos resultados observacionales. The exposure to artificial gravity (AG) through human centrifugation is the basis of the treatment called gravity therapy (GT), in which the mechanical stimulation over the vessel wall, induces the synthesis and release of prostacyclin. It has been used for more than four decades in Uruguay in the treatment of different vascular-based pathologies. In patients with systemic sclerosis (SSc) it has shown good benefits and excellent safety profile over the years. However, there is a lack of knowledge in the scientific community about GT and its results. To evaluate the effectiveness of GT in cutaneous and vascular involvement, in the quality of life and functional capacity and its safety profile in patients with SSc. It is a descriptive and retrospective study of patients with SSc assisted in an autoimmunity center in Montevideo, treated with GT in the last 10 years. Fifty patients were included, 48 women (96%) and 2 men (4%) with a mean age of 62 ± 12 years. The mean time of evolution of SSc at the time of inclusion in the study at the beginning of GT was 6.8 ± 3.2 years and 2.8 ± 3.2 years respectively. After GT, a significant improvement in the modified Rodnan skin score (mRSS) was observed (pre-GT 19.2 ± 8.7 vs post-GT 5.4 ± 5.0, P <.05), which was not related to the time of disease progression at the beginning of GT nor to the skin extension or immunological profile. The degree of improvement post-GT was related to a higher initial mRSS (R = 0.84, P <.05). Also, a significant improvement was observed in the number of patients with puffy fingers (pre-GT 50% vs post-GT 20% patients, P <.05), but not in telangiectasias, pitting scars or sclerodactyly. The severity of Raynaud's phenomenon significantly decreased (pre-GT: grade 3-4, 43/48 (89.6%) patients vs post-GT: grade ≤ 2, 42/47 (89.4%) patients, P <.05) as well as the vascular pain measured with VAS (0-10 scale) (pre-GT: 7.6 ± 2.2 vs post-TG: 1.4 ± 1.2, P <.05). The healing of digital ulcers was also recorded. Regarding the results reported by patients, 97% reported improvement in the quality of life and 89.5% improvement in the ability to carry out activities of daily living. No significant adverse effects were recorded. GT improved cutaneous and vascular involvement, the quality of life and the functional capacity in patients with SSc with an excellent safety profile. Randomized, controlled clinical trials are needed to corroborate these observational results. [ABSTRACT FROM AUTHOR]

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

Background: 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. Objective: 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). Methods: 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. Results: 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. Conclusions: Normal nailfold dermoscopy with the absence of four easy‐to‐observe criteria predicts normal NVC with an excellent PPV. [ABSTRACT FROM AUTHOR]

Objective: Anti–histidyl‐transfer RNA synthetase (Jo‐1) antibodies are associated with myositis as well as different extramuscular organ complications comprising the anti‐synthetase syndrome. This study aimed to clarify the relationship between anti–Jo‐1 epitope recognition patterns and specific clinical features of this syndrome. Methods: B cell epitope mapping was performed via enzyme‐linked immunosorbent assay in 180 patients who were anti–Jo‐1 antibody‐positive using overlapping peptides/protein fragments spanning the amino‐terminal 151 amino acids of Jo‐1 as substrate antigens. Statistical associations with clinical features were assessed through rank‐sum, correlation, and cluster analyses. Results: The level of reactivity against subfragments spanning amino acids 1–151 of Jo‐1 paralleled that of full‐length Jo‐1, confirming the immunodominance of this amino‐terminal region. The corresponding frequencies of reactivity to peptides 1 (amino acids [aa] 1–21), 3 (aa 27–47), 4 (aa 40–60), 10 (aa 118–138), and 11 (aa 131–151) were 6.1%, 42.5%, 6.8%, 6.7%, and 20.3%. While anti–full‐length Jo‐1 antibodies were significantly associated with Raynaud phenomenon, anti‐fragment A2 (aa 1–60) and A3 (aa 1–90) antibodies were associated with proximal muscle weakness, Raynaud phenomenon, arthritis, and sicca syndrome. Anti‐fragment A4 (aa 1–120) and A5 (aa 1–151) antibodies were also associated with sicca syndrome. Peptide 1 (aa 1–21) antibodies were associated with Raynaud phenomenon and dysphagia. Whereas anti‐peptide 3 (aa 27–47) antibodies were also linked to Raynaud phenomenon, anti‐peptide 9 (aa 105–125) antibodies were associated with mechanic's hands. Conclusion: Autoantibodies targeting different amino‐terminal subfragments and/or peptides of Jo‐1 were associated with specific clinical features of the anti‐synthetase syndrome, demonstrating the biomarker potential of B cell epitope profiling in this disorder. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate salivary gland involvement in patients with anti-centromere antibody (ACA)-positive primary Sjögren's syndrome (pSS). We retrospectively evaluated 134 patients with pSS. Patients were divided into four groups based on the results of ACA and SSA antibodies. We compared clinical manifestations, laboratory findings, salivary gland shear wave elastography, minor salivary gland biopsy results, and EULAR Sjögren's syndrome disease activity index (ESSDAI) scores among the four groups. A total of 134 patients were classified as having pSS and divided into three groups based on serum ACA and anti-SSA antibody status: ACA + SSA + , ACA + SSA-, ACA-SSA + , and seronegative. The primary analysis focused on comparing the clinical and SWE findings between the ACA + SSA + and ACA + SSA- groups. In the double-positive group, SWE revealed fewer minor salivary glands along with higher mean (Emean) and maximum (Emax) values of Young's moduli than those in the ACA-negative group. Patients in the positive group had increased occurrence of Raynaud's phenomenon, liver involvement, and a higher incidence of malignancy (P < 0.05). ACA-positive pSS patients are a subgroup with different clinical manifestations and more pronounced involvement of the minor salivary glands. SWE findings revealed that ACA-positive patients exhibit significantly higher mean and maximum stiffness values compared to ACA-negative patients, indicating more extensive glandular fibrosis and involvement. These results underscore the utility of SWE as a valuable method for evaluating salivary gland pathology and supporting the stratification of pSS patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders characterized by progressive proximal muscle weakness and varying extra-muscular manifestations. The latest 2017 EULAR/ACR criteria classify them into subgroups. This study aims to evaluate the role of nailfold capillaroscopy (NFC) as a diagnostic and prognostic tool in IIMs by comparing capillaroscopic patterns across different IIM subtypes. Methods: We conducted an observational, cross-sectional study at the Institute of Rheumatology in Belgrade, analyzing 90 patients diagnosed with IIMs per the 2017 EULAR/ACR criteria. Patients were categorized into dermatomyositis (DM) (n = 37), polymyositis (PM) (n = 35), amyopathic dermatomyositis (ADM) (n = 13), and juvenile dermatomyositis (JDM) (n = 5). A control group of 35 patients with primary Raynaud's phenomenon was also included. NFC findings, clinical manifestations, and laboratory data were compared across the groups. Results: In DM, 81.9% exhibited a scleroderma capillaroscopic pattern, which was also present in 76.9% of ADM patients. In PM, the most common pattern was nonspecific changes (48.6%). JDM patients showed a high prevalence of scleroderma changes (n = 4 (80%)). Scleroderma patterns correlated with Gottron's papules, heliotrope rash, periungual erythema, Raynaud's phenomenon, and interstitial lung disease (ILD). No significant differences were found in laboratory parameters across capillaroscopic groups, except for a higher prevalence of anti-Jo1 antibodies in patients with nonspecific capillaroscopic changes. Conclusions: NFC is a valuable tool for differentiating IIM subtypes and correlating clinical manifestations with specific capillaroscopic patterns. The high prevalence of scleroderma changes in DM and ADM suggests their potential as a diagnostic and prognostic marker in IIMs. Further research with larger cohorts is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Acute digital ischemia is a rare manifestation of anti‐synthetase syndrome in the absence of Raynaud's phenomenon. A high index of suspicion may result in early diagnosis and better clinical outcomes. A 61‐year‐old male patient was admitted to the hospital for worsening arthralgias with morning stiffness lasting hours, as well as left sided headaches, and jaw pain while eating. He had significant weight loss and subjective fever at home. Multiple fingers and toes were noted to be ischemic. His laboratory workup was pertinent for significantly elevated inflammatory markers, and mild Creatinine kinase elevation. Chest imaging and later lung biopsy were notable for organizing pneumonia. Conventional angiogram showed evidence of significant digital disease without collaterals. Subsequent autoimmune screening tests with extended myositis‐specific and myositis‐associated panels revealed a strongly positive anti‐PL‐12 antibody and moderately positive anti‐ SSA‐52KD IgG ab. After ruling out infectious etiologies and malignancy, anti‐synthetase syndrome (ASyS) diagnosis was considered in the presence of ischemic digits, organizing pneumonia, polyarthralgia, constitutional symptoms, increased inflammatory markers and positive antibodies. The patient was treated with high dose prednisone and mycophenolate mofetil along with amlodipine and sildenafil for digital vasodilation. Acute digital ischemia may be the first manifestation of ASyS with ILD. A high index of suspicion is warranted for early diagnosis and better outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease characterized by microvascular alterations, immunopathology, and widespread fibrosis involving various organs. It is considered difficult to treat due to several reasons: complex pathogenesis, heterogeneity, late diagnosis, limited treatment options for certain organ manifestations, lack of personalized medicine. This review presents the heterogeneity, survival and organ manifestations with their risk factors of systemic sclerosis and their current treatment options, while drawing attention to difficult-to-treat forms of the disease, based on literature indexed in PubMed. Despite recent advances in the management of SSc over the last decades, the disease presents significant morbidity and mortality. Although available treatment protocols brought significant advancements in terms of survival in SSc-associated interstitial lung disease and pulmonary arterial hypertension, less success has been achieved in the treatment of Raynaud's phenomenon and digital ulcers and the results are modest in case of heart, gastrointestinal, and renal manifestations. There are patients who do not respond to treatment and deteriorate even with adequate therapy. They can be considered difficult-to treat (D2T) cases. We have created a possible score system based on the individual organ manifestations and highlighted treatment options for the D2T SSc category. [ABSTRACT FROM AUTHOR]

Objectives To comprehensively review systematic reviews of prevalence, incidence, and mortality of Raynaud's, Sjögren's and Scleroderma, and to identify any research gaps. Methods An umbrella review of English language systematic reviews was undertaken using PubMed and Embase (OVID) covering the period 2000–2023 (PROSPERO CRD42023434865). The estimate and its corresponding 95% confidence interval were reported when available from each systematic review. The quality of systematic reviews was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) tool. A narrative synthesis was undertaken. Results Seventeen systematic reviews were identified, of which 1 was for RP, 5 for Sjögren's and 11 for Scleroderma. There were some high-quality systematic reviews for Sjögren's and mortality of Scleroderma. However, there were only low-quality systematic reviews of prevalence and incidence of RP and Scleroderma. Furthermore, there were no systematic reviews for the mortality of RP. For RP, the pooled prevalence was 4850 per 100 000; pooled annual incidence was 250 per 100 000. For Sjögren's, prevalence was 60–70 per 100 000; annual incidence was 6.92 per 100 000 and the pooled standardized mortality ratio ranged from 1.38 to 1.48. For Scleroderma, pooled prevalence ranged from 17.6 to 23 per 100 000; annual incidence was 1.4 per 100 000; and the pooled standardized mortality ratio ranged from 2.72 to 3.53. Conclusion The outcomes of RP were less well described compared with Sjögren's and Scleroderma. There was a lack of high-quality systematic reviews for the prevalence and incidence of RP and Scleroderma. Therefore, further studies and systematic reviews with rigorous case definitions, assessing different ethnic groups are warranted in this area. [ABSTRACT FROM AUTHOR]

Background: Calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome is an acronym for the clinical features that are seen. Its etiology is unknown, affecting women three times more than men. CREST syndrome is often diagnosed by systemic symptoms. However, oral manifestations could be helpful in the early diagnosis of the disease. Less than 20 cases of CREST syndrome with oral symptoms were described. Objective: To report a case of a 26‐year‐old female, who was diagnosed with CREST syndrome based on findings of the oral mucosa. Case report: Clinical examination revealed sclerodactyly and nail alterations. Oral findings were associated with hypochromic and paleness mucosa. The tongue was strongly rigid and reddish areas compatible with telangiectasias were found. The mouth opening was particularly compromised. Histological findings were suggestive of systemic sclerosis in the context of CREST syndrome. Considering the available diagnosis criteria, this case was diagnosed as CREST syndrome based on oral manifestations. Conclusions: Oral manifestations of CREST syndrome could help in early clinical diagnosis, preventing a delay in the onset of an aggressive form of the disease. Accurate referrals of patients to specialists are needed for a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

A 58‐year‐old female smoker diagnosed with myelodysplastic syndrome (MDS) presented with Raynaud's phenomenon and a "scleroderma‐like" pattern on nailfold capillaroscopy. The capillaroscopic abnormalities were observed across all fingers, including those without clinical manifestations of onychomycosis. Over a two‐year follow‐up, there was no evidence of clinical or serological progression toward a connective tissue disease, particularly systemic sclerosis. This case underscores the potential contributory role of MDS and smoking in the development of microvascular dysfunction, presenting as capillaroscopic abnormalities in the absence of an underlying autoimmune disorder. [ABSTRACT FROM AUTHOR]

The editorial discusses the challenges in defining and monitoring the progression of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). The study evaluated four different definitions of SSc-ILD progression and found that they were not interchangeable, leading to confusion in clinical practice and research. The findings suggest the need for standardized definitions to guide treatment decisions and improve outcomes for patients with SSc-ILD. The study highlights the importance of further research and initiatives like the European Reference Networks to address the complexities of rare diseases such as SSc-ILD. [Extracted from the article]

The article discusses a survey conducted among primary Raynaud's patients in the community to understand their GP consultations and prescribed treatments. The survey found that about 90% of patients visited their GP for Raynaud's, with 50% being prescribed medication. The most common medication prescribed was calcium channel blockers. The study highlights the need for further research on primary RP to better understand patient needs and treatment patterns. [Extracted from the article]

Lithium Carbonate is an effective treatment for affective disorders, but has a range of side effects. This case report highlights a rare side effect of Raynaud's phenomenon following initiation of Lithium therapy in a patient with recurrent depressive disorder. He was commenced on Lithium therapy to treat severe treatment resistant depression with psychotic symptoms when alternative treatments trialled were ineffective. He had no other risk factors or known aetiological causes for development of Raynaud's phenomenon. Symptoms resolved on discontinuation of Lithium and re-emerged on recommencement. Previous case series have shown Lithium effectively treating vasospastic disorders such as cluster headache and Raynaud's phenomenon. However, a paradoxical reaction to those previously described was induced in this case. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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 realworld 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objective: Chronic interstitial lung disease (ILD) occurs rarely with systemic lupus erythematosus (SLE) as compared with other connective tissue diseases. This multicentric retrospective study of patients with SLE‐ILD from the OrphaLung and French SLE networks during 2005–2020 aimed to describe the characteristics of patients with SLE‐ILD and analyse factors associated with prognosis. Methods: We analysed data for 89 patients with SLE‐ILD (82 women, 92.1%) (median age at SLE diagnosis: 35 years [interquartile range 27–47]). All patients met the 2019 EULAR/ACR criteria for the diagnosis of SLE. Results: Forty two (47.2%) patients were positive for anti‐ribonuclear protein antibodies and 45 (50.6%) for anti SSA/Ro antibodies. A total of 58 (65.2%) patients had another connective tissue disease: Sjögren's syndrome (n = 33, 37.1%), systemic sclerosis (n = 14, 15.7%), inflammatory myopathy (n = 6, 6.7%), or rheumatoid arthritis (n = 6, 6.7%). ILD was diagnosed along with SLE in 25 (28.1%) patients and at a median of 6 (0–14) years after the SLE diagnosis. The most frequent CT pattern was suggestive of non‐specific interstitial pneumonia (n = 41, 46.0%) with or without superimposed organizing pneumonia. After a median follow‐up of 86.5 [39.5–161.2] months, 18 (20.2%) patients had died and 6 (6.7%) underwent lung transplantation. The median 5‐year and 10‐year transplantation‐free survival were 96% (92–100) and 87% (78–97). In total, 44 (49.4%) patients showed ILD progression. Cutaneous manifestations and Raynaud's phenomenon were associated with better survival. Only forced vital capacity was significantly associated with survival and ILD progression. Conclusion: ILD is a rare manifestation of SLE with good overall prognosis but with possible risk of ILD progression. Patients with SLE‐ILD frequently have another connective tissue disease. [ABSTRACT FROM AUTHOR]

Juvenile scleroderma (JS) is a group of diseases characterized by thickened skin and fibrosis. There are two main types: juvenile localized scleroderma (JLS) and juvenile systemic sclerosis (JSSc). The cause of JS is believed to be immune system dysregulation, leading to inflammation, vascular damage, and fibrosis. The management of JS is difficult, but the use of tofacitinib, a Janus kinase (JAK) inhibitor, has shown promise in treating the disease. This study presents three cases where tofacitinib effectively improved skin symptoms and reduced joint stiffness in pediatric patients with severe forms of morphea and JSSc. The authors suggest that tofacitinib could be a valuable treatment option for these patients, but further research is needed. [Extracted from the article]

Hand-arm vibration is a common occupational exposure that causes neurological impairment,myalgia, and vibrationinduced Raynaud's phenomena or vibration white fingers (VWF). The pathological mechanism is largely unknown, though several mechanisms have been proposed, involving both immunological vascular damage and defective neural responses. The aim of this study was to test whether the substances interleukin-33 (IL-33), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), endothelin-1 (ET-1), C-C motif chemokine ligand 20 (CCL20), calcitonin, and thromboxane (TXA2) changed before and after occupational hand-arm vibration exposure. 38 full-time shift workers exposed to hand-arm vibration were recruited. All the participants underwent medical examinations regarding symptoms of Raynaud's phenomena. In 29 of the participants, the concentration of IL-33, MDC, IL-10, ET- 1, CCL20, calcitonin, and TXA2 was measured before and after a workday. There was a significant increase in ET-1 and calcitonin concentration and a decrease in the CCL20 concentration after the work shift in all participants. In the group suffering from VWF, but not in the non-VWF group, MDC was statistically significantly lower before the work shift (p = .023). The VWF group also showed a significant increase in MDC after the work shift. Exposure to occupational hand-arm vibration is associated with changes in ET-1, calcitonin, and MDC concentration in subjects suffering from vibration white fingers, suggesting a role of these biomarkers in the pathophysiology of this condition. [ABSTRACT FROM AUTHOR]

Objective Patients with secondary RP show a wide range of symptoms depending on the condition of vascular structures. If the symptoms are localized to specific fingers and angiography reveals a discrete segment of occlusion of a proper digital artery, we perform proper digital artery reconstruction with an interposition vein graft. The objective of this study was to evaluate the results of the surgery in patients with chronic hand ischaemia. Methods A retrospective chart review was performed on patients who underwent proper digital artery reconstruction. Each digit that underwent grafting was analysed separately. The results of surgical intervention and recurrence based on patient symptoms were evaluated. Cox proportional hazards regression models were used to identify independent risk factors associated with recurrence, and the Kaplan–Meier method was used to predict the 5-year recurrence-free rate. Results A total of 79 digits from 57 patients were included in this study. The majority of patients demonstrated resolution of ischaemic pain and ulceration (97.5% and 95.3%, respectively). Recurrence occurred in 16 (20.3%) patients during the follow-up period. In two cases (2.5%) surgery had no effect. In the multivariate Cox regression analysis, smoking and concomitant periarterial sympathectomy were significant factors associated with recurrence. In the Kaplan–Meier analysis, the 5-year recurrence-free rate in the total study population was 69.3%. Conclusions Digital artery reconstruction using an interposition vein graft is an effective procedure for improving ischaemic pain and ulceration in patients with RP. Smoking and concomitant periarterial sympathectomy were significantly associated with recurrence. [ABSTRACT FROM AUTHOR]

Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results In total 1054 patients were included (DM, n  = 405; ASyS, n  = 649). In the ASyS cohort, 31% (n  = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P  < 0.001), whereas higher frequency of any of four DM-type rashes—heliotrope rash (n  = 248, 61% vs n  = 90, 44%), violaceous rash (n  = 166, 41% vs n  = 57, 9%), V-sign (n  = 124, 31% vs n  = 28, 4%), and shawl sign (n  = 133, 33% vs n  = 18, 3%)—differentiated DM from ASyS-DMskin (all P  < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n  = 67, 17%) compared with ASyS (n  = 21, 3%) and ASyS-DMskin (n  = 7, 3%) cohorts (both P  < 0.001). Conclusion DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management. [ABSTRACT FROM AUTHOR]

The 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. The 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. A 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. The 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. A 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. [ABSTRACT FROM AUTHOR]

Background: Despite emotional stress being recognised as a key trigger for Raynaud's phenomenon episodes, research in the area is still in its infancy. Aims: This study investigated the role of psychological factors relating to symptom severity and quality of life, and differences between Raynaud's types (primary and secondary) to further inform the development of intervention in this field. Method: A cross-sectional design was used. Two hundred and ten adults with Raynaud's completed an online questionnaire measuring stress, anxiety, depression, anxiety sensitivity, beliefs about emotions, symptom severity and quality of life. Results: Primary and secondary Raynaud's groups differed in anxiety (p <.004), symptom severity (p <.001) and quality of life (p <.001). Stepwise multiple regressions indicated anxiety and Raynaud's type explained 23% variance in hand symptom severity (p <.001); anxiety, Raynaud's type and anxiety sensitivity explained 29% variance in symptom severity (global impact, p <.001); depression, Raynaud's type and anxiety sensitivity explained 32% variance in quality of life (p <.001). Conclusions: Results highlight the importance of psychological factors in Raynaud's phenomenon, indicating possible targets for treatment. Interventions such as cognitive behavioural therapy, which target both physical and psychological wellbeing, bear some promise as an adjuvant therapy for this group. [ABSTRACT FROM AUTHOR]

Introduction: A rupture of the skin accompanied by erosion of the subcutaneous tissue beneath is called an ulcer. The adjacent muscle and bone may be further compromised by this breach. A full-thickness skin defect that has not significantly re-epithelialized for longer than four weeks is referred to be a chronic ulcer. Wounds with "full thickness depth" and a "slow healing tendency" are referred to as ulcerations. In general, the delayed healing tendency cannot be fully explained by depth and size alone. But brought on by a pathologic reality at the root that must be eliminated in order to promote recovery. Aims: To research the treatment of lower leg ulcers and their clinic pathological characteristics. Materials and methods: The present study was a Prospective observational study. This study was conducted from January 2023 to December 2023 at the Department of General Surgery, Private Medical Medical College & Hospital. Out of 80 patients, 65 patients were included in this study. Result: In our study, 8 patients presented with varicose veins the cause of ulcers is of venous etiology. The value of z is 1.002. The value of p is < .001. The result is significant at p < .05. In our study 5 patients had Raynaud's phenomena and the cause of ulcers are of arterial etiology. The value of z is 0.899. The value of p is < .001. The result is significant at p < .05. In our study out of 21 patients with loss of sensation the causes of ulcers are diabetic followed by arterial and venous etiology. The value of z is 1.074. The value of p is < .001. Conclusion: We draw the conclusion that, in addition to adding to the expanding body of information on lower leg ulcers, our clinic pathological investigation emphasizes the significance of a thorough, multidisciplinary approach to diagnosis and treatment. Through the implementation of evidence-based treatment options and an attention to the intricate interaction of variables that lead to ulcer formation, our goal is to enhance patient quality of life while mitigating the prevalence of chronic wounds in our communities. [ABSTRACT FROM AUTHOR]

Background In patients with systemic sclerosis, a chronic autoimmune illness, the immune system becomes dysregulated, blood vessels are damaged, and organs and skin become fibrotic. Biomarkers are essential in clinical practice because they allow for accurate diagnosis, the prediction of disease development, and the assessment of the effectiveness of treatment. The aim of the study is to determine the variety aspects of clinical and epidemiological factors of Iraqis' systemic sclerosis. Methods A cohort of 39 individuals diagnosed with Systemic Sclerosis (SSc) were involved in the current cross-sectional investigation. The research was carried out from December 15, 2022, to May 30, 2023, utilizing a specifically crafted questionnaire. Results Overall, 100% of the people who took part had thicker skin. Following this were Raynaud's phenomenon (97.5%), abnormal nail fold capillaries (94.9%), telangiectasia (85.8%), oral puckering, dysphagia, and puffy fingers (79.5%), and finally shortness of breath and sclerodactyly (77%). Additionally, 73.8% of participants had ILD, and 19.0% had pulmonary hypertension. ANA positivity was seen in 90% of the patients. There is a strong association between the presence of anti-Sc1-70 antibodies and DcSSc. In the limited form, only one case (2.56%) tested positive, while 23 cases (58.97%) tested positive. This association was shown to be statistically significant with a p-value < 0.001. Patients with limited cutaneous systemic sclerosis (LcSSc) were much more likely than those with diffuse cutaneous systemic sclerosis (DcSSc) to have anti-centromere antibodies (ACA), with rates of 17.95% for LcSSc and 10.25% for DcSSc (p = 0.037). Conclusion SSc has a higher frequency among the female population. Typically, the first clinical manifestation is Raynaud's phenomenon, but other symptoms may manifest at any stage of the disease's unpredictable course. [ABSTRACT FROM AUTHOR]