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Acta Dermato-venereologica Jun 2024
Topics: Humans; Female; Aged; CREST Syndrome; Facial Dermatoses; Biopsy; Skin
PubMed: 38850086
DOI: 10.2340/actadv.v104.40419 -
Chest Jun 2024The 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery...
BACKGROUND
The 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery pressure (mPAP) > 20 mmHg at right heart catheterization (RHC). Previously, patients with a mPAP between 21 and 24 mmHg were classified in a "grey zone" of unclear clinical significance.
RESEARCH QUESTION
What is the diagnostic performance of the main parameters used for PH screening in detecting systemic sclerosis (SSc) patients with mPAP 21-24 mmHg at RHC?
STUDY DESIGN AND METHODS
SSc patients from the European Scleroderma Trials and Research (EUSTAR) database with available tricuspid annular plane systolic excursion (TAPSE), systolic PAP (sPAP) and mPAP data were included. Patients with mPAP 21-24 mmHg and patients with mPAP ≤ 20 mmHg were considered for the analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated.
RESULTS
TAPSE/sPAP was lower in the group of SSc patients with mPAP 21-24 mmHg than in non-PH group [0.58 (0.46-0.72) mm/mmHg vs 0.69 (0.57-0.81) mm/mmHg, p < 0.01]. No difference was found in other parameters between the two groups. Diffusing capacity of the lungs for carbon monoxide (DL) < 80% of the predicted value had the highest sensitivity (88.9%) and NPV (80%), but the lowest specificity (18.2%) and PPV (30.8%) in detecting SSc patients with mPAP 21-24 mmHg. TAPSE/sPAP < 0.55 mm/mmHg had the highest specificity (78.9%), PPV (50%) and accuracy (68.1%); its NPV was of 75.4%, while its sensibility 45.1%.
INTERPRETATION
DL < 80% of the predicted value is the parameter with the highest sensitivity and NPV in detecting SSc patients with mPAP 21-24 mmHg. TAPSE/sPAP < 0.55 mm/mmHg has the highest specificity, PPV and accuracy and, therefore, can be a useful additional parameter to decrease the number of unnecessary RHC.
PubMed: 38849072
DOI: 10.1016/j.chest.2024.05.010 -
Clinical and Experimental Medicine Jun 2024Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR)...
Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, β-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. 79 Caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% BsmI, 77% FokI) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study.Trial registration. DRKS00032768, date: 05.10.2023, retrospectively registered.
Topics: Humans; Receptors, Calcitriol; Scleroderma, Systemic; Female; Bone Density; Male; Middle Aged; Aged; Adult; Prevalence; Osteoporosis; Absorptiometry, Photon; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Bone Diseases, Metabolic; Genotype
PubMed: 38847864
DOI: 10.1007/s10238-024-01385-1 -
Cureus May 2024Juvenile systemic sclerosis (JSSc) is a rare autoimmune disorder that primarily affects children and adolescents. It is thought to be caused by a confluence of...
Juvenile systemic sclerosis (JSSc) is a rare autoimmune disorder that primarily affects children and adolescents. It is thought to be caused by a confluence of immunological, environmental, and genetic variables. The disease is characterized by excessive collagen production. It can result in symptoms such as shortness of breath, chest pain, difficulty swallowing, high blood pressure, and kidney problems. Although calcinosis cutis is common in systemic sclerosis, it is very rare in JSSc. We report the case of a 14-year-old female who presented with complaints of breathlessness for four days and multiple lesions in the sacral region for two months. She underwent surgical excision for calcinosis cutis in dependent regions. Early diagnosis and treatment of the condition are of immense importance in preventing mortality.
PubMed: 38841009
DOI: 10.7759/cureus.59729 -
Nature Medicine Jun 2024Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein,... (Randomized Controlled Trial)
Randomized Controlled Trial
Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren's syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, -6.3 ± 0.6; PBO, -4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, -1.8 ± 0.2; PBO, -0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 .
Topics: Humans; Sjogren's Syndrome; CD40 Ligand; Double-Blind Method; Female; Middle Aged; Male; Adult; Aged; Treatment Outcome
PubMed: 38839899
DOI: 10.1038/s41591-024-03009-3 -
F1000Research 2024Pulmonary involvement is a major cause of internal organ complication and the leading cause of death in patients with systemic sclerosis (SSc). This study aimed to...
BACKGROUND
Pulmonary involvement is a major cause of internal organ complication and the leading cause of death in patients with systemic sclerosis (SSc). This study aimed to demonstrate the characteristics of pulmonary function (PF) in Thai patients with SSc and the association between PF and body mass index (BMI) and anti-topoisomerase (anti-Scl70).
METHODS
All patients diagnosed with SSc in our tertiary care teaching hospital database between 2016 and 2021 were reviewed and analyzed.
RESULTS
Of 211 SSc patients, 128 patients who underwent the PF test were enrolled; 102 (79.7%) were female. The mean age was 54 years. The median BMI for all patients was 21.7 kg/m . Regarding anti-Scl70, 10.9% of patients were positive, 7.8% were negative, and the status was unreported for 81.3%. The mean (SD) forced expiratory volume in one second (FEV1) forced vital capacity (FVC) ratio was 0.8 (0.1). The mean (SD) % predicted values of FEV1, FVC, and diffusing capacity of the lungs for carbon monoxide (DLCO) were 76.3 (16.3), 69.1 (15.8), and 75.5 (22.8), respectively. A restrictive spirometry pattern (RSP) was found in 78.8% of the patients. DLCO had a moderate positive linear correlation with FVC (r=0.50, p <0.001) and a moderate negative linear correlation with BMI (r=-0.36, p <0.001). However, there was no correlation between FVC and BMI. There was no statistical difference in demographic data or the presence of anti-Scl70 among patients with or without RSP.
CONCLUSIONS
RSP is common among Thai patients with SSc. However, the power of using demographic data and the presence of anti-Scl70 to determine the probability of pulmonary involvement remains limited.
Topics: Humans; Female; Scleroderma, Systemic; Male; Middle Aged; Retrospective Studies; Thailand; Lung; Respiratory Function Tests; Body Mass Index; Adult; Vital Capacity; Aged; Forced Expiratory Volume; Southeast Asian People
PubMed: 38835937
DOI: 10.12688/f1000research.146498.2 -
Cureus May 2024Scleroderma is an autoimmune disease that affects connective tissue. Keratoconus (KC) is a rare ocular condition that may appear alongside scleroderma. Contact lenses...
Scleroderma is an autoimmune disease that affects connective tissue. Keratoconus (KC) is a rare ocular condition that may appear alongside scleroderma. Contact lenses are an essential visual aid for KC patients, especially in advanced cases. However, scleroderma patients may face difficulties using them due to finger-related disabilities. Corneal collagen cross-linking (CXL) is a crucial treatment used to prevent corneal thinning and visual deterioration in progressive KC. However, the potential trigger of corneal melt and delayed healing following CXL in KC patients with scleroderma is a matter of concern. We present a case of a patient with KC and scleroderma who underwent CXL without any complications.
PubMed: 38826919
DOI: 10.7759/cureus.59431 -
BioRxiv : the Preprint Server For... May 2024The cardinal feature of systemic sclerosis (SSc) is skin thickening and tightening. Targetable mechanisms for skin features remain elusive. Drugs successful in treating...
BACKGROUND
The cardinal feature of systemic sclerosis (SSc) is skin thickening and tightening. Targetable mechanisms for skin features remain elusive. Drugs successful in treating internal organ manifestations have failed efficacy in skin. Dermal white adipose tissue (DWAT) is amongst the understudied contributors to skin manifestations. This study proposes the role of sine oculis homeobox homolog 1 (), a gene previously unrecognized as a contributor to dermal lipoatrophy characteristic of early skin fibrosis in SSc.
METHODS
Skin gene expression of was analyzed in the GENISOS and PRESS SSc cohorts. Correlation analysis was performed with Spearman rank analysis. Novel mouse models were developed using the Cre-loxp system to knock out in all cells and mature adipocytes. Subcutaneous bleomycin was used to model early DWAT atrophy and dermal fibrosis characteristic of SSc.
FINDINGS
was upregulated in SSc skin, the expression of which correlates with adipose-associated genes and molecular pathways. Genetic deletion of in all cells in mice challenged with bleomycin abrogated end-stage fibrotic gene expression and dermal adipocyte shrinkage. Adipocyte specific deletion was able to attenuate the early increase in skin thickness, a hallmark of experimental skin fibrosis. Further studies revealed a link between elevated SIX1 and increased expression of SERPINE1 and its protein PAI-1 which are known pro-fibrotic mediators.
INTERPRETATION
This work identifies as an early marker of skin fibrosis in SSc. We also demonstrate a causative role of in skin fibrosis by promoting adipocyte loss and show that deletion of in adipocytes has the potential of impacting early disease progression.
PubMed: 38826482
DOI: 10.1101/2024.05.22.595271 -
The Journal of Rheumatology Jun 2024Concerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We...
OBJECTIVE
Concerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We conducted a systematic review to evaluate the effects of radiotherapy on SSc outcomes and radiotherapy-related toxicity.
METHODS
MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched for SSc and radiotherapy. Inclusion criteria were SSc diagnosis, subsequent cancer development, and radiotherapy exposure. Outcomes were SSc manifestations (cutaneous thickening, pulmonary fibrosis, and SSc flare) and radiotherapy toxicity (acute and late) using Common Terminology Criteria for Adverse Events for grading. Grade 1 and 2 toxicities were categorized as nonsevere and grade 3 to 5 toxicities as severe.
RESULTS
Of 121 patients with SSc undergoing radiotherapy (mean age 56.4 years, 83.3% female, median radiotherapy dose 50 Gy), most did not show worsened SSc skin thickening (74.5%) or pulmonary complications (74%) post radiotherapy. In retrospective studies, the average rates of acute adverse effects were 57.3% for nonsevere and 25.8% for severe, whereas the rates of late adverse effects were 32.4% for nonsevere and 24% for severe.
CONCLUSION
Although most patients with SSc do not exhibit significant worsening of SSc manifestations post radiotherapy, there is a variable risk of acute and late toxicity. These findings suggest that although radiotherapy may be a viable option for patients with cancer with SSc, it requires caution.
PubMed: 38825361
DOI: 10.3899/jrheum.2023-1235 -
Iranian Journal of Allergy, Asthma, and... Apr 2024Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays...
Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc.
Topics: Adult; Female; Humans; Male; Middle Aged; Actins; Cells, Cultured; Dexamethasone; Fibroblasts; Fibrosis; Gene Expression Regulation; Interferon Regulatory Factor-1; Interferon-gamma; Interleukin-6; Myofibroblasts; Scleroderma, Systemic
PubMed: 38822514
DOI: 10.18502/ijaai.v23i2.15325