Systemic Sclerosis Research Articles

Quantitative Assessment of Systemic Sclerosis–Related Interstitial Lung Disease via 3D‐Imaging

ABSTRACTBackground and ObjectiveInterstitial lung disease (ILD) is a leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). The disease course of SSc‐related ILD (SSc‐ILD) is heterogeneous, and several risk‐based models have been developed. This study aimed to quantitatively measure volume loss and disease extent and subsequently evaluate their associations with the development of end‐stage lung disease (ESLD).MethodsLung volume (LV) and disease extent were retrospectively and quantitatively evaluated in two cohorts (exploratory: n = 70; validation: n = 42) using high‐resolution computed tomography at the time of SSc‐ILD diagnosis, compared to controls (n = 70). LV was quantitatively measured using three‐dimensional imaging (3D‐image) and standardised by predicted forced vital capacity (standardised LV). The ratio of the normally attenuated LV (range, −950 to −750 Hounsfield units) to the whole‐LV (NL%) was also measured using 3D‐image. The associations of these variables with ESLD were evaluated.ResultsVolume loss and normal lung area loss were noted in patients with SSc‐ILD compared with controls, especially in the lower lobes. Meanwhile, extended ILD lesions without volume reduction were observed in the upper lobes. Both decreased standardised LV and NL% were associated with ESLD development, and age and NL% were significant risk factors for ESLD independent of pulmonary function test parameters and standardised LV. A composite model consisting of age and NL% successfully stratified patients with SSc‐ILD based on the risk of ESLD.Conclusion3D‐image may be a useful technique for assessing disease severity and predicting the risk for ESLD in patients with SSc‐ILD. image

Validity and psychometric characteristics of the Duruöz Hand Index (DHI) with systemic sclerosis

Objective: The Duruöz Hand Index (DHI) is a self-report questionnaire originally developed to assess hand function in rheumatoid arthritis patients and validated for various rheumatic conditions. The aim of the study is to evaluate the validity and psychometric features of the DHI in patients with systemic sclerosis (SSc). Methods: SSc patients diagnosed using EULAR/ACR 2013 criteria were included in study. Hand functionality was assessed using the DHI, Hand Functional Index (HFI) and visual analog scales (VAS) for disability and handicap. Overall disability and quality of life were measured using the Health Assessment Questionnaire (HAQ) and Short Form-36 (SF-36). Reliability (Cronbach’s alpha and ICC) and validity (face, content, convergent and divergent) were also analyzed and correlations with other measures assessed for construct validity of the DHI were examined. Results: Seventy-three patients were included in the study, 78.1% were female. The baseline mean DHI score was 31.2 (SD: 20.2). Completion and calculation of the questionnaire were easy and took 5 min and 30 s, respectively. The Cronbach’s alpha coefficient for internal consistency was 0.973 and the ICC for test-retest reliability was 0.993 (95%CI 0.981–0.997), suggesting that the DHI has high internal consistency and a high degree of reliability. Cognitive debriefing showed that the DHI is clear, understandable, relevant, and covers many domains of daily life, indicating good face and content validity. The DHI demonstrated good to moderate correlations with functional measures indicating convergent validity and moderate to non-significant correlations with non-functional parameters that supported divergent validity. Cronbach’s alpha was 0.973, indicating excellent internal consistency. Conclusion: In SSc patients, specific tools for assessing hand function are lacking. The DHI is a practical, reliable and valid measurement tool for both clinical assessment and research in this disease affecting skin, tendons, subcutaneous tissue and arthritis.

Belumosudil in diffuse cutaneous systemic sclerosis: a randomised, double-blind, open-label extension, placebo-controlled, Phase 2 study.

To determine the efficacy, safety, and pharmacodynamics of belumosudil in patients with diffuse cutaneous systemic sclerosis (dcSSc) treated with background immunosuppressive therapies. Eligible patients were randomised 1:1:1 to receive belumosudil 200 mg once daily (QD) or twice daily (BID), or placebo for 28 weeks (double-blind period). After unblinding, the patients who received belumosudil continued the same dose, whereas the patients who received placebo were re-randomised for one of the belumosudil doses for 24 weeks (open-label extension). Thirty-five and 31 patients were treated in the double-blind and open-label periods, respectively. The study was terminated prematurely, and target enrolment was not met. The primary end point, of CRISS score ≥0.60 at week 24, did not exhibit an efficacy signal in the belumosudil vs placebo groups (odds ratio: 1.06 [0.19-5.82; p= 0.9472] for the QD, and 0.39 [0.07-2.35; p= 0.3078] for the BID group). Belumosudil was well tolerated and exhibited similar safety profiles in both double-blind and open-label periods. Tissue-based RNA-sequencing analysis revealed FOXP3 upregulation and STAT3, IL23A, and TGF-β downregulation in patients with CRISS score ≥0.60, which supported the mechanism of action of belumosudil. In blood and tissue samples, trends of decreased fibrosis biomarker levels were seen in belumosudil-treated group vs placebo. Efficacy signal for belumosudil could not be detected. Signalling pathway modulation analysis supported the mechanism of action of belumosudil. A trend for decreased fibrosis-related biomarkers was observed in the belumosudil-treated group. ClinicalTrials.gov, https://clinicaltrials.gov, NCT03919799.

Sex differences in the risk of incident systemic sclerosis: a nationwide population-based study with subgroup analyses

Although higher prevalence of systemic sclerosis (SSc) in women than in men is well-known, it is unclear to what degree women are at higher risk of developing incident SSc. This study aims to assess the risk of incident SSc comparing women vs. men, and to identify subsets of individuals in whom the risk difference according to sex is more prominent. An analysis of a Korean nationwide cohort of 9,894,996 individuals was conducted. All individuals were followed up from 2009 to 2019. Cox proportional hazard models were used to assess the risk of incident SSc comparing women vs. men. Subgroup analysis was conducted by stratifying individuals according to multiple covariates. The absolute risk of SSc in men (i.e., background risk) was 0.004% (95% CI 0.003–0.004), and the absolute risk of SSc in women was 0.025% (95% CI 0.023–0.027). The absolute risk difference between women and men was 0.021% (95% CI 0.019–0.024). Women had a significantly higher risk of incident SSc than men (adjusted hazard ratio [aHR], 5.275; 95% confidence interval, 4.346–6.403). The effect size was more pronounced in middle-aged individuals (aHR 5.020 [< 40 years] vs. 5.868 [40–64 years] vs. 2.734 [≥ 65 years]; p-interaction < 0.001); those without abdominal obesity (aHR 5.863 vs. 3.658; p-interaction = 0.005); those who did not exercise regularly (aHR 5.701 vs. 3.932; p-interaction = 0.030); and those without hypertension (aHR 5.996 vs. 4.053; p-interaction = 0.010) or dyslipidemia (aHR 5.857 vs. 3.330; p-interaction = 0.001). Women had a 5-fold higher risk of incident SSc than men. The higher risk was more prominent in middle-aged individuals, those without abdominal obesity, those who do not exercise regularly, and do not have hypertension or dyslipidemia.

Lysine Demethylase 1 Has Demethylase-Dependent and Non-Canonical Functions in Myofibroblast Activation in Systemic Sclerosis

Lysine Demethylase 1 Has Demethylase-Dependent and Non-Canonical Functions in Myofibroblast Activation in Systemic Sclerosis

Long-term Prognostic Value of Left and Right Ventricular Systolic Function on Cardiovascular Magnetic Resonance Imaging in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disorder associated with a high risk of cardiovascular diseases. We aimed to determine the long-term prognostic value of left and right ventricular (LV and RV) systolic dysfunction in SSc patients with clinically suspected cardiac disease. We conducted a retrospective cohort study of consecutive adults with SSc who had cardiovascular magnetic resonance imaging (CMR) for suspected cardiac disease. We assessed two CMR measures of LV and RV function, ejection fraction (EF) and feature tracking-derived global longitudinal strain (GLS), and investigated their associations with the long-term incidence of a composite endpoint of death or major adverse cardiac events (MACE). In 151 patients (median age 58 years, 81% women) who had CMR at a median of 3.6 years after diagnosis, the median LVEF was 58.0%, and the median LVGLS was -15.7%. The median RVEF was 57.0%, and the median RVGLS was -16.2%. Over a median follow-up of 4.7 years, 69 patients experienced the composite endpoint of death or MACE. LVGLS was independently associated with the composite endpoint (hazard ratio [HR] 1.08 per 1% worsening; 95% confidence interval [CI] 1.01-1.15; p = 0.018), while LVEF was not. Similarly, RVGLS was independently associated with the composite endpoint (HR 1.08 per 1% worsening; 95% CI 1.01-1.15; p = 0.017), while RVEF was not. In patients with SSc and clinically suspected cardiac disease, worse LVGLS and RVGLS on CMR were independently associated with death or MACE, while LVEF and RVEF were not.

Hand function impairment in Systemic sclerosis: Outcomes, Mechanisms and Experience (HANDSOME) – a longitudinal observational multicentre study protocol

IntroductionThe majority of all patients with systemic sclerosis (SSc) experience hand function impairment. The exact cause for this impairment is yet unknown. As impaired hand function hugely impacts daily functioning...

Using a smartphone app to monitor Raynaud's attacks and quantify skin colour changes-towards objective outcome measures for Raynaud's.

Our overall aim was to develop a smartphone app to collect photographic images of Raynaud's phenomenon (RP) attacks alongside patient reported outcome measures (PROMs). Specific objectives included assessing the feasibility of patients documenting RP attacks using mobile phones, developing image analysis methods to document colour change, and comparing photographic parameters to 'non-imaging' app and paper diary parameters. Study 1: 36 patients with systemic sclerosis (SSc)-related RP photographed RP attacks over 15 days as well as completing an RP paper diary. Study 2: 40 patients with either SSc-related or primary RP used a smartphone app to collect, over 15 days, photographic images and data including frequency and severity of attacks. In both studies, mean colour change during each attack (indicating severity) was quantified by the Bhattacharyya distance. Study 1: 24/36(67%) patients completed the study of whom 22 photographed at least one RP attack (median number of attacks 12.5, range 1-53). 18/24(75%) patients preferred phone to paper diary documentation. 'Photographic' and 'paper diary' frequency (but not severity) of attacks correlated strongly: correlation co-efficient 0.71, 95% confidence intervals 0.41-0.87; p= 0.002. Study 2: 36/40(90%) completed the study, providing 1747 usable images from 456 RP attacks. ANOVA analysis demonstrated that RP colour change was significantly different with different values of RP attack severity (p< 0.001). Collecting photographs of RP attacks and PROMS via a smartphone app was feasible and preferred by patients to data collection via paper diary, providing proof-of-concept for validation studies of app-based outcome measures for RP.

A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis.

Interstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARSWHEP because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells. Structural analysis of HARSWHEP confirmed a well-organized helix-turn-helix motif. This motif bound specifically and selectively to neuropilin-2 (NRP2), a receptor expressed by myeloid cells in active sites of inflammation, to inhibit expression of proinflammatory receptors and cytokines and to down-regulate inflammatory pathways in primary human macrophages. In animal models of lung injury and ILD, including bleomycin treatment, silicosis, sarcoidosis, chronic hypersensitivity pneumonitis, systemic sclerosis, and rheumatoid arthritis-ILD, HARSWHEP reduced lung inflammation, immune cell infiltration, and fibrosis. In patients with sarcoidosis, efzofitimod treatment resulted in down-regulation of gene expression for inflammatory pathways in peripheral immune cells and stabilization of inflammatory biomarkers in serum after steroid tapering. We demonstrate the immunomodulatory activity of HARSWHEP and present preclinical data supporting ongoing clinical development of the biologic efzofitimod based on HARSWHEP in ILD.

Characteristics and management of systemic sclerosis-related osteomyelitis: a retrospective cohort study

Digital ulcers in patients with systemic sclerosis (SSc) can be complicated by SSc-related osteomyelitis (SRO). The microbiological data and optimal management of SRO remain unclear. This single-center retrospective study involved patients with SSc aged 18 or older from April 2005 to March 2022. Diagnosis of SRO was based on clinical presentation and MRI findings. The accuracy of the superficial swab culture results was estimated using the bone culture as a reference. Temporal changes in local signs for up to a year were collected, and their association with (1) duration of antimicrobial therapy (> 6 weeks) or (2) surgical interventions was assessed using univariable analyses. Among the 2,126 patients, 46 (2.2%) were diagnosed with SRO. In seven patients whose swab and bone cultures were both available, two (28.6%) had swab cultures identifying all the organisms detected in bone cultures. Resolution of local inflammatory signs consistently preceded wound closure. Three months after therapy initiation, prolonged antimicrobial therapy was not significantly associated with the resolution of local inflammatory signs (16/19 [84.2%] vs. 12/14 [85.7%]; P = 1.00), and surgical intervention was not significantly associated with wound dehiscence (6/9 [66.7%] vs. 20/24 [83.3%]; P = 0.36). Superficial swab cultures may not reliably reflect the true causative organism of SRO. Prolonging antimicrobial therapy beyond six weeks may be of little benefit for patients with SRO when local inflammatory signs improve. Surgical intervention may be a safe and effective option for selected patients with SRO.

Identification of biomarkers and immune infiltration associated with sexes in systemic sclerosis: a bioinformatics and machine learning.

This study aimed to identify key candidate genes associated with the sexes of patients with systemic sclerosis (SSc). Skin gene expression datasets from patients with SSc and healthy controls (GSE181549 and GSE130955) were retrieved from the GEO database. GSE181549 served as the testing set, while the GSE130955 was used for validation. Differentially expressed genes (DEGs) between SSc and normal skin samples were identified using Limma, stratified by sex in the GSE181549. Bioinformatics analyses were performed to evaluate the DEGs, and machine learning techniques were applied to identify sex-specific. In male samples from the testing set, 80 DEGs were upregulated and 20 were downregulated, while in female samples, 94 DEGs were upregulated and 12 were downregulated. Functional enrichment analysis indicated that these DEGs are potentially implicated in sex-specific SSc pathogenesis. Machine learning identified 10 marker genes in males samples and 12 in females. Immune infiltration analysis revealed a significant increase in M0 and M1 macrophages and a decrease in M2 macrophages and resting dendritic cells in male SSc samples. In female SSc samples, memory B cells, plasma cells and M1 macrophages were significantly elevated, whereas resting CD4 memory T cells were notably reduced. Patients with SSc exhibit distinct sex-specific differences in DEGs, marker genes, and immune infiltration profiles.

Target organ connective tissue: the variability of systemic fibrosis

The group of systemic fibrosing connective tissue diseases is remarkably diverse, comprising awide spectrum of distinct entities. Central to their pathogenesis is the fibroblast, which, when activated by exogenous or endogenous triggers, can pathologically overproduce components of the extracellular matrix or exhibit uncontrolled proliferation. Systemic sclerosis, recognized as the prototype of systemic fibrosing diseases, belongs to the connective tissue diseases. Despite considerable advancements in the understanding of its pathogenesis, diagnosis, and treatment over recent years, systemic sclerosis remains one of the most fatal conditions among inflammatory rheumatic diseases. Its hallmark features include vasculopathy, systemic fibrosis, and autoimmunity, with common organ involvement affecting the skin, lungs, heart, gastrointestinal tract, kidneys, and musculoskeletal system. Therapeutic strategies focus on improving perfusion, controlling inflammation, and implementing antifibrotic measures. Key differential diagnoses include eosinophilic fasciitis, mixed connective tissue disease, and other overlap syndromes, which often require immunomodulatory treatment. Innovative developments in the field suggest apotential paradigm shift in the treatment of inflammatory rheumatic diseases, with cell-based therapies like CD19-depleting chimeric antigen receptor (CAR) Tcell therapy showing promising early outcomes. Other systemic fibrosing diseases include scleromyxedema and scleroedema adultorum Buschke, both of which belong to the mucinoses and contribute further to the complexity of this disease group.

Connective tissue disease-associated interstitial lung disease: an approach to treatment amidst an expanding evidence base.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) comprises a heterogenous group of conditions characterised by immune-mediated fibro-inflammatory pulmonary injury. Although the disease course is variable, CTD-ILD can progress to respiratory failure and thus has a profound impact on morbidity and mortality. Systemic sclerosis (SSc), rheumatoid arthritis, idiopathic inflammatory myositis, Sjogren disease systemic lupus erythematosus and mixed connective tissue disease can all manifest or present with ILD. Histological injury in CTD-ILD is diverse and pharmacological management, when indicated, is typically centred around corticosteroids and various immunosuppressive or anti-fibrotic agents. Until recently, treatment decisions have been extrapolated from the evidence base available for SSc-related ILD. Many recent trials and prospective studies have evaluated treatment options in a range of CTD-ILD, thus guiding therapeutic intervention. Amidst an expanding evidence base, this comprehensive review describes new management strategies in CTD-ILD with a focus on evidence from clinical trials. Supportive care and minimising treatment-associated adverse effects remains paramount in this population with complex respiratory pathology and frequent co-morbidities.

The relationship between connective tissue disease and autoantibody positivity in pneumoconiosis cases.

This correlation has been studied since the 1930s, and it is believed that exposure to silica can lead to various autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. The exact mechanisms behind this link remain unclear. This study aimed to evaluate the prevalence of connective tissue diseases (CTD) and positive autoantibodies in pneumoconiosis patients and the association between radiological categorization and autoantibodies. The study included 317 subjects. Pneumoconiosis cases' clinical, radiographic classification, and laboratory results were compared to autoantibody-positive and autoantibody-negative cases, and CTD cases were examined. The prevalence of the CTD in pneumoconiosis was 6%. Sjögren syndrome (n = 5) was the most common disease associated with pneumoconiosis. Autoantibodies were found in 83 (26.2%) pneumoconiosis cases. Antinuclear antibody positivity was highest (n = 75; 23.65%). More than 1 autoantibody was positive in 23 cases (7.25%), while rheumatoid factor was positive in 9 cases (2.84%). It has been shown that autoantibody positivity is 2.79 times higher in cases with category 3 and above pneumoconiosis. The prevalence of CTD and autoantibody positivity associated with pneumoconiosis is higher than in the general population. The presence of autoantibody positivity is associated with advanced pneumoconiosis disease.

Systemic sclerosis complicated by azathioprine-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder: A case report.

Lymphoproliferative disorders are rare complications in patients with autoimmune diseases who are receiving immunosuppressive therapy. This case report describes a 74-year-old man with diffuse cutaneous systemic sclerosis, anti-RNA polymerase III antibodies, and interstitial pneumonia. The patient's condition initially improved with prednisolone and intravenous cyclophosphamide, followed by maintenance therapy with azathioprine, nintedanib, and macitentan for pulmonary hypertension. Thirty months after initiating AZA, the patient developed nodules and ulcers in the left lower jaw and philtrum. Skin biopsy confirmed diffuse large B-cell lymphoma. Discontinuation of azathioprine led to the resolution of the ulcers, and no other lesions were found. This case highlights the risk of iatrogenic immunodeficiency-associated lymphoproliferative disorders in patients with systemic sclerosis, particularly in those with anti-RNA polymerase III antibodies, who are known to have an increased risk of malignancy. Although methotrexate-associated lymphoproliferative disorders are well documented in patients with rheumatoid arthritis, this is the first reported case of azathioprine-associated lymphoproliferative disorder in systemic sclerosis. These findings emphasise the importance of close monitoring of malignancies, including lymphoproliferative disorders, in patients with systemic sclerosis undergoing immunosuppressive therapy.

Isolated Adrenocorticotropic Hormone Deficiency Mimicking Systemic Sclerosis: A Diagnostic Challenge in Patients With Rheumatoid Symptoms

Isolated Adrenocorticotropic Hormone Deficiency Mimicking Systemic Sclerosis: A Diagnostic Challenge in Patients With Rheumatoid Symptoms

The Salt & Pepper Enigma: A Cutaneous Cipher to Seronegative Systemic Sclerosis with Myopathy.

The Salt & Pepper Enigma: A Cutaneous Cipher to Seronegative Systemic Sclerosis with Myopathy.

Respiratory tract lining fluid copper content contributes to pulmonary oxidative stress in patients with systemic sclerosis

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs, mostly affecting young and middle-aged women. Significant questions remain as to its pathogenesis, especially the triggers for the associated interstitial lung disease (SSc-ILD). We examined the extent to which SSc and SSc-ILD were related to oxidative stress and altered metal homeostasis at the air-lung interface. Methods In this case-control study, we recruited 20 SSc patients, of which 11 had SSc-ILD. Eighteen healthy individuals were recruited as age-matched healthy controls, for a total of 38 study participants. Low molecular weight antioxidants (ascorbate, urate and glutathione), metal transport and chelation proteins (transferrin and ferritin) and metals (Fe and Cu) concentrations, including a measure of the catalytically active metal pool, were determined in respiratory tract lining fluid (RTLF) collected by bronchoalveolar lavage from the SSc group and compared with healthy controls. Results In the SSc group, 14 individuals were of female sex (70%) and the median age was 57 years (range 35–75). We observed evidence of oxidative stress in the RTLFs of SSc patients, characterised by increased concentrations of glutathione disulphide (GSSG, P&lt;0.01), dehydroascorbate (DHA, P&lt;0.05) and urate (P&lt;0.01). This was associated with elevated RTLF Fe (P=0.07) and Cu (P&lt;0.001), and evidence of a catalytic metal pool, demonstrated by an enhanced rate of ascorbate oxidation in the recovered lavage fluid (p&lt;0.01). Cu concentrations were significantly associated with the ascorbate depletion rate (r=0.76, P&lt;0.001), and GSSG (r=0.38, P&lt;0.05) and protein carbonyl (r=0.44, P&lt;0.01) concentrations. Whilst these markers were all increased in SSc patients, we found no evidence for an association with SSc-ILD. Conclusions These data confirm the presence of oxidative stress in the airways of SSc patients and, for the first time, suggest that an underlying defect in metal homeostasis at the air-lung interface may play a role in disease progression.

A new therapeutic pathway in autoimmune diseases: chimeric antigen receptor T cells (CAR-T) targeting specific cell subtypes or antigen-specific B lymphocytes—a brief review

In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells expressing target antigens. The objective here was to discuss the prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) to deplete pathogenic autoantibodies by eliminating B lymphocytes and plasma cells. B cells play a crucial role in the pathogenesis of AID through the production of autoantibodies, cytokine dysregulation, antigen presentation, and regulatory dysfunction. In AID with numerous autoreactive clones against various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, and systemic sclerosis, CAR-T targeting CD19/CD20 and B-cell maturation antigen (BCMA) have shown success in preclinical and clinical studies, representing an innovative option for refractory patients when standard treatments fail. The suppression of B lymphocytes reactive against specific antigens using cytolytic T cells carrying a chimeric autoantibody receptor (CAAR-T) offers a promising approach for managing various AIDs, especially those with characterized pathogenic autoantibodies, such as pemphigus vulgaris, myasthenia gravis, and anti-NMDAR autoimmune encephalitis. CAAR-T allows the elimination of autoreactive B lymphocytes without compromising the general functionality of the immune system, minimizing common side effects in general immunosuppressive therapies, including immunobiologicals and CAR-T. In vitro, preclinical, and clinical (phase 1) studies have demonstrated the efficacy and specificity of CAR-T and CAAR-T in several AIDs; however, extensive clinical trials (phase 3) are required to assess their safety and clinical applicability. These advances promise to enhance precision medicine in the management of AIDs, offering personalized treatments for individual patients.

Precision Medicine in Rheumatology: The Role of Biomarkers in Diagnosis and Treatment Optimization

Rheumatic diseases encompass a wide range of autoimmune and inflammatory disorders, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and systemic sclerosis (SSc). These conditions often result in chronic pain, disability, and reduced quality of life, with unpredictable disease courses that may lead to joint destruction, organ damage, or systemic complications. Biomarkers, defined as measurable indicators of biological processes or conditions, have the potential to transform clinical practice by improving disease diagnosis, monitoring, prognosis, and treatment decisions. While significant strides have been made in identifying and validating biomarkers in rheumatic diseases, challenges remain in their standardization, clinical utility, and integration into routine practice. This review provides an overview of the current state of biomarkers in rheumatic diseases, their roles in clinical settings, and the emerging advancements in the field.