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Journal of Vascular Surgery Cases and... Aug 2024Arterial thoracic outlet syndrome (aTOS) is a rare, but potentially, limb-threatening condition that is often misdiagnosed. We present the case of a 29-year-old man who...
Arterial thoracic outlet syndrome (aTOS) is a rare, but potentially, limb-threatening condition that is often misdiagnosed. We present the case of a 29-year-old man who was initially managed under the presumption of primary Raynaud's phenomenon for >1 year before the correct diagnosis of aTOS, and the delay in diagnosis was complicated by substantial distal thromboembolic occlusion. Successful staged treatment included thoracic outlet decompression, subclavian artery aneurysm repair with subclavian-to-axillary bypass, anticoagulation, and an unconventional axillary-to-ulnar artery bypass. This report highlights the diagnostic challenges of aTOS and the importance of considering it in patients with Raynaud's phenomenon and vaso-occlusive symptoms.
PubMed: 38812728
DOI: 10.1016/j.jvscit.2024.101508 -
Turkish Journal of Medical Sciences 2024The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis...
BACKGROUND/AIM
The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19.
MATERIALS AND METHODS
In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews.
RESULTS
The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively.
CONCLUSION
This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.
Topics: Humans; COVID-19; Scleroderma, Systemic; Female; Male; Middle Aged; Retrospective Studies; Adult; SARS-CoV-2; Risk Factors; Lung Diseases, Interstitial; Hospitalization; Comorbidity; Aged; Respiratory Insufficiency; Disease Progression
PubMed: 38812619
DOI: 10.55730/1300-0144.5768 -
RMD Open May 2024Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge...
OBJECTIVE
Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already disturbed in patients with very early SSc (veSSc) when fibrosis is not yet clinically detectable.
METHODS
42 patients with veSSc, defined as the presence of Raynaud's phenomenon and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, not meeting the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc, were compared with healthy controls (HCs, n=29). ECM degradation (BGM, C3M, C4M and C6M) and ECM formation biomarkers (PRO-C3, PRO-C4 and PRO-C5) were measured in serum using ELISAs. A cross-sectional analysis at baseline and a longitudinal analysis was performed.
RESULTS
Compared with HC, veSSc patients showed a strongly dysregulated turnover of type III and IV collagens (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was higher in veSSc than in HC (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower (p=0.002). In an ROC analysis, biomarkers of type III and IV collagen excellently distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001.
CONCLUSION
These findings indicate ECM remodelling as a very early phenomenon of SSc occurring in parallel with microvascular and autoimmune changes. Biomarkers of type III and IV collagens distinguished between veSSc patients and HC, indicating them as potential biomarkers for the detection of veSSc.
Topics: Humans; Scleroderma, Systemic; Biomarkers; Female; Male; Middle Aged; Adult; Extracellular Matrix; Collagen; Case-Control Studies; Cross-Sectional Studies; ROC Curve; Aged; Biglycan; Collagen Type III
PubMed: 38806188
DOI: 10.1136/rmdopen-2023-003306 -
Archivos Argentinos de Pediatria May 2024Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations...
Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations are less frequently involved. This study focused on describing the characteristics of a series of women with Raynaud's phenomenon of the nipple. Through medical record review and direct communication with patients, data from 12 women diagnosed with Raynaud's phenomenon of the nipple between 2016 and 2023 were collected and analyzed. The following variables were assessed: age, symptoms, triggering factors, treatment, and duration of symptoms. In this case series, Raynaud's phenomenon of the nipple in breastfeeding women was more common among primiparous women around 10 days after delivery; pain was severe and, in most cases, improved with local and/or drug treatment, and did not limit the duration of breastfeeding.
PubMed: 38771559
DOI: 10.5546/aap.2023-10280.eng -
The Journal of Allergy and Clinical... May 2024Transient receptor potential melastatin subfamily member 4 (TRPM4) is a broadly expressed, calcium-activated, monovalent cation channel that regulates immune cell...
BACKGROUND
Transient receptor potential melastatin subfamily member 4 (TRPM4) is a broadly expressed, calcium-activated, monovalent cation channel that regulates immune cell function in mice and cell lines. Clinically however, partial loss or gain of function mutations in TRPM4 lead to arrythmia and heart disease, with no documentation of immunological disorders.
OBJECTIVE
To characterize the functional cellular mechanisms underlying the immune dysregulation phenotype in a proband with a mutated trpm4 gene.
METHODS
We employ a combination of biochemical, cell biological, imaging, omics analyses, flow cytometry, and gene editing approaches.
RESULTS
We report the first human cases with complete loss of the TRPM4 channel leading to immune dysregulation with frequent bacterial and fungal infections. Single cell and bulk RNAseq point to altered expression of genes affecting cell migration, specifically in monocytes. Inhibition of TRPM4 in T cells and the THP1 monocyte cell line reduces migration. More importantly primary T cells and monocytes from the TRPM4 patients migrate poorly. Finally, CRISPR knockout of TRPM4 in THP1 cells greatly reduces their migration potential.
CONCLUSION
Our results demonstrate that TRPM4 plays a critical role in regulating immune cell migration, leading to increased susceptibility to infections.
PubMed: 38750824
DOI: 10.1016/j.jaci.2024.02.026 -
Mediterranean Journal of Rheumatology Mar 2024To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response.
OBJECTIVES
To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response.
METHODS
All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed.
RESULTS
Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders.
CONCLUSION
ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.
PubMed: 38736967
DOI: 10.31138/mjr.230323.cca -
EBioMedicine May 2024Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and...
BACKGROUND
Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus.
METHODS
This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5-DM outbreak.
FINDINGS
Sixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response.
INTERPRETATION
A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.
FUNDING
This work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.
PubMed: 38723554
DOI: 10.1016/j.ebiom.2024.105136 -
International Journal of General... 2024Systemic Sclerosis (SSc) is a rare connective tissue disorder characterized by autoimmunity, fibrosis, and vasculopathy that affects the skin and internal organs,...
PURPOSE
Systemic Sclerosis (SSc) is a rare connective tissue disorder characterized by autoimmunity, fibrosis, and vasculopathy that affects the skin and internal organs, including the gastrointestinal tract, particularly the esophagus. This article highlights the characteristics and clinical symptoms of esophageal involvement in patients with SSc.
PATIENTS AND METHODS
This study was conducted between November 2022 to August 2023, including 26 already diagnosed cases of SSc in the Department of Rheumatology and Rehabilitation and Kurdistan Center for Gastroenterology and Hepatology-Sulaymaniyah, Iraq. Esophageal involvement was investigated using esophageal manometry, esophagogastroduodenoscopy (EGD), and 24-hour impedance-pH monitoring.
RESULTS
Females were significantly predominant ( = 0.019) regarding the symptoms; 76.9% of the patients had heart burn, 76.9% dysphagia, 73.1% water brush, and 69.2% regurgitation. In total, 69.2% of the patients showed erosive gastrointestinal reflux disease (GERD) on EGD, 76.9% had decreased lower esophageal sphincter pressure (DLESP) and decreased distal esophageal peristaltic contractions (DDEPC) on esophageal manometry, and 84.6% had reflux on pH monitoring. Raynaud's phenomenon is the most common and typically the earliest clinical manifestation of SSc. The presence of erosive GERD was found to significantly increase the risk of developing dysphagia (B = 4.725, = 0.014, OR = 3.482) and regurgitation (B = 3.521, = 0.006, OR = 4.030).
CONCLUSION
It is crucial to take gender-specific considerations into account when diagnosing and managing esophageal complications in patients with systemic sclerosis (SSc). Additionally, employing various diagnostic assessments to detect esophageal involvement during SSc is essential. Erosive GERD has been identified as a risk factor that contributes to the development of dysphagia and regurgitation in individuals with SSc.
PubMed: 38711827
DOI: 10.2147/IJGM.S448421 -
Frontiers in Medicine 2024Lung involvement in the context of idiopathic inflammatory myopathies has significant impact on outcome; early and accurate diagnosis is important but can be difficult...
BACKGROUND
Lung involvement in the context of idiopathic inflammatory myopathies has significant impact on outcome; early and accurate diagnosis is important but can be difficult to achieve. In particular, patients without clinically evident muscle involvement pose a significant diagnostic challenge.
METHODS
A computer-assisted search was conducted to identify patients with amyopathic interstitial lung disease associated with the presence of myositis-specific autoantibodies. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features at presentation.
RESULTS
Of the 35 patients with amyopathic interstitial lung disease associated with myositis-specific autoantibodies, the median age was 65 years (range 43-78) and 20 were women (57%). Of the patients, 34% had previously visited the rheumatology department. Presenting symptoms consisted of dyspnea (94%), cough (43%), and arthritis (23%). Raynaud phenomenon, "mechanic hands," Gottron papules, and inspiratory crackles were present in 23, 31, 9, and 74% of patients, respectively. After a detailed history, none of the patients reported muscle weakness, while four (11%) exhibited increased CK levels; of these four, two had a concomitant increase in aldolase levels. Median FVC was 79% predicted (range: 49-135) and median DLco was 50% predicted (range: 17-103). HRCT pattern was suggestive of an alternative to UIP pattern in 31/33 (94%) patients; the most common imaging patterns were NSIP (49%) and NSIP/OP (39%).
CONCLUSION
In patients with NSIP and NSIP/OP pattern, the presence of amyopathic interstitial lung disease associated with myositis-specific autoantibodies should be considered even in the absence of clinical evident myositis.
PubMed: 38711778
DOI: 10.3389/fmed.2024.1392659 -
Microvascular Research May 2024Nailfold Videocapillaroscopy (NVC) is a valuable tool in the differential diagnosis of Raynaud's phenomenon (RP), present in certain Rheumatic diseases (RD). Knowing...
BACKGROUND
Nailfold Videocapillaroscopy (NVC) is a valuable tool in the differential diagnosis of Raynaud's phenomenon (RP), present in certain Rheumatic diseases (RD). Knowing that many people have cardiovascular risk factors (CVRF), the main objective was to demonstrate that CVRF and carotid plaques produce NVC alterations.
METHODS
Cross-sectional unicentric study carried out from 2020 to 2023. Four groups were formed: subjects with RD and RP, participants with RD without RP, subjects with RP without RD and finally participants without RP or RD (study group). Each subject exhibiting CVRF presented only a single risk factor. The variables collected were: sociodemographic, CVRF (diabetes, tobacco, alcohol (ALC), obesity (OBE), dyslipidemia and arterial hypertension (AH)), diseases, RP, treatments, tortuosities and NVC alterations (ramified capillaries, enlarged capillaries, giant capillaries, haemorrhages and density loss) and carotid ultrasound (CU).
RESULTS
402 subjects were included (76 % women, mean age 51 ± 16 years), 67 % had CVRF, 50 % RP and 38 % RD. Tortuosities were present in 100 % of CVRF participants. A statistically significant association was found between the presence of CVRF and all the NVC alterations: ramified capillaries (OR = 95.6), enlarged capillaries (OR = 59.2), giant capillaries (OR = 8.32), haemorrhages (OR = 17.6) and density loss (OR = 14.4). In particular, an association was found between giant capillaries with AH (p = 0,008) and OBE (p 〈0,001), and haemorrhages and density loss with ALC and OBE (p < 0,001). On the other hand, 40 subjects presented CU plaques (9.9 %), associated with enlarged capillaries (OR = 8.08), haemorrhages (OR = 4.04) and ramified capillaries (OR = 3.01). The pathological intima-media thickness was also associated with haemorrhages (OR = 3.14).
CONCLUSIONS
There is a clear association between CVRF and ultrasound atherosclerotic findings in carotid with NVC alterations. These findings are of special interest for a correct NVC interpretation and to avoid false positives in the diagnosis of primary and secondary RP.
PubMed: 38701966
DOI: 10.1016/j.mvr.2024.104693