BACKGROUND/OBJECTIVE:Sicca symptoms, including ocular and oral dryness, are frequently reported among patients with systemic sclerosis (SSc). Yet most studies have focused on patients with associated Sjögren disease (SjD) and data on SSc patients with isolated sicca symptoms remain limited. Therefore, we aimed to (i) investigate the characteristics of SSc patients with and without sicca symptoms, after excluding individuals with associated SjD or other potential causes of dryness, and (ii) identify factors independently associated with the presence of sicca manifestations. MATERIALS AND METHODS:This single-center retrospective observational study included consecutive SSc patients attending the Department until December 2024. Demographic, clinical and serological data were extracted from medical records. Sicca symptoms were defined as the presence of either dry eye or dry mouth symptoms documented in the medical records, using a structured approach. Multivariable logistic regression analysis was performed to determine variables significantly associated with sicca symptoms. RESULTS:In total, 237 SSc patients were included, 25.7% of whom reported sicca symptoms. In univariate analysis, age, female sex, arthralgias, left ventricular diastolic dysfunction (LVDD), and ratio of residual volume to total lung capacity (RV/TLC) ≥40% were associated with sicca symptoms. In multivariate analysis, only female sex [OR: 4.808 (95% CI: 1.088-15.308)] and RV/TLC≥40% [OR: 4.413 (95% CI: 1.982-9.826)] remained independent predictors of sicca manifestations. CONCLUSION:Sicca symptoms are common in SSc, even in the absence of SjD, and are characterized by female predominance and small airway involvement. SSc patients with isolated sicca symptoms may represent a distinct clinical phenotype.

Spondyloarthritis (SpA) is a chronic inflammatory disease involving axial (ax-SpA), and peripheral joints (p-SpA). It mainly affects young individuals and symptoms begin before the age of 45 years. Late onset (LO) ax-SpA, presenting after the age of 50, is rare. It is usually underdiagnosed in favor of other disorders, which are very common in this population. A 70-year-old woman presented with fever of unknown origin (FUO), back pain, malaise, weakness and high acute phase reactants, without any other clinical or laboratory findings. After an intensive and extensive investigation, to exclude several diseases and disorders, our patient, despite being old and almost asymptomatic for SpA features was diagnosed as having LO-axSpA. The patient was treated successfully with adalimumab. We discuss the differential diagnosis of FUO in an elderly woman with constitutional symptoms and elevated inflammatory markers. This is the first case of LO-axSpA presenting with FUO, therefore, physicians must be aware of rare manifestations of ax-SpA in the elderly population. Rigorous and extensive investigation is required to reach the correct diagnosis.

In the decades of the 1980s and 1990s, before the onset of biologic therapies for rheumatoid arthritis (RA) management, there was a significant number of patients who did not achieve remission or low disease activity (LDA), due to limited therapeutic choices. At that time, only some conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), along with steroids, were used. Nowadays, despite the progress of RA management with the introduction of biologic (b) and targeted synthetic (ts) DMARDs, which showed significant clinical improvement and retardation of radiological damage, unmet needs of RA treatment still exist. On the other hand, the concept of treat-to-target (T2T) approach and tight control monitoring of disease activity, are considered now the cornerstone for achieving remission or LDA in RA patients. Several clinical trials confirmed the efficacy and safety of csDMARDs using the tight control and T2T strategies. Methotrexate is the fundamental drug for RA management and in combination with other csDMARDs, with or without steroids, it has proven to be efficacious and safe and less expensive in comparison to newer biologic therapies. Furthermore, MTX demonstrated cardioprotective effects and reduced the risk of cardiovascular events in RA patients Therefore, there is a potential for improving treatment strategies with conventional therapies in the management of early RA. Optimal and early use of csDMARDs controls disease activity similarly to biologic therapies and is less expensive.

To investigate the lipid profile and subclinical atherosclerosis in patients with undifferentiated connective tissue disease (UCTD), in comparison with rheumatoid arthritis (RA) and healthy individuals. This cross-sectional controlled study included 30 patients with UCTD, treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), 59 patients with RA receiving csDMARDs, and 31 age- and sex-matched healthy controls. All participants had no history or presence of coronary artery disease, hypertension, diabetes mellitus, dyslipidemia, thyroid disease, smoking, and none received diuretics, cholesterol-lowering drugs, or other agents affecting the lipid profile. Fasting serum lipid parameters such as total cholesterol (TC), triglycerides (TGL), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured in all patients and controls. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (cIMT) using ultrasonography. UCTD patients exhibited significantly lower TC and HDL-C levels compared with controls (204.4 ± 43.0 mg/dL vs 238 ± 41.4 mg/dL, p < 0.004 and 50.6 ± 9.5 mg/dL vs 61.3 ± 13.3 mg/dL, p < 0.002 respectively). They also presented with increased cIMT compared to healthy controls (0.8 [0.6–1.5] mm vs 0.6 [0.5–0.7] mm, p < 0.001). No differences were observed in TGL and LDL-C among UCTD and healthy controls. RA patients demonstrated higher cIMT (in unadjusted analyses) and HDL-C compared to UCTD patients (0.9 [0.8–1.0] mm vs 0.8 [0.6–1.5] mm, p < 0.001 and 56.8 ± 15.2 mg/dL vs 50.6 ± 9.5 mg/dL, p < 0.004 respectively). However, after multivariable linear regression analysis adjusting for age, sex, ESR, and disease duration, disease type was not independently associated with cIMT (β = 0.02, 95

Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease affecting mostly the small joints of the hands and feet. Extra-articular manifestations (EAMs) comprise the involvement of the skin, eyes, heart and lung. Among them, subcutaneous rheumatoid nodules (RN) are a common manifestation of systemic disease. However, disorders such as rheumatoid nodulosis, multicentric reticulohistocytosis (MRH) and others present subcutaneous nodules, similar to those seen in RA patients. A 41-year-old woman with a 10-year history of untreated RA, presented complaining of pain and tenderness in the small joints of the hands and feet. Past medical and family history were unremarkable. She presented swelling and tenderness on all metacarpophalangeal joints (MCPs) bilaterally and had multiple widespread subcutaneous RN affecting almost all the fingers of the hands, as well as, the Achille's tendons in a symmetrical manner. She had elevated levels of acute phase reactants and high titres of autoantibodies. Hand x-rays revealed severe erosive changes affecting all MCPs joints bilaterally. Thus, in this review we discuss the differential diagnosis of subcutaneous RN and their role in RA disease activity. This is an educational case of a patient with RA and extensive subcutaneous RN affecting the upper and lower extremities. To this end, physicians must be familiar and recognise early these signs which reflect RA disease activity and treat appropriately.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects the synovial membrane of the joints in a symmetrical pattern, leading to cartilage and bone damage. It affects 0.5-1% of the general population, predominantly women in their fourth to fifth decades of life. In addition to its impact on the joints, RA has numerous extra-articular manifestations involving the skin, eyes, heart and lung. Among these, pulmonary manifestations play a pivotal role in morbidity and mortality. RA can affect all anatomical compartments of the lung such as the airways, lung parenchyma, pulmonary vasculature and pleura. Among these, parenchymal disease that manifests as interstitial ling disease (ILD) is the most serious. The etiopathogenesis of RA remains elusive with multiple underlying genetic and environmental risk factors implicated. Cigarette smoking has been strongly associated with an increased risk of developing RA in genetically susceptible individuals, particularly those carrying the shared epitope of the human leucocyte antigen (HLA) DRB1* alleles. Smoking induces chronic pulmonary inflammation, promotes protein citrullination in the lungs, leads to the generation of anti-citrullinated antibodies and contributes to the development of RA. In this review we discuss the various manifestations of RA associated lung disease, methods of screening, the pathophysiology of RA in relation to the lung and recent advances in treatment.

INTRODUCTION:Spondyloarthritis (SpA) includes a group of chronic inflammatory disorders affecting the axial skeleton and/or peripheral joints. The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is pivotal in cytokine-mediated signaling, contributing to SpA pathogenesis. AREAS COVERED:Cytokine inhibitors were the first biological therapies used in SpA. However, not all patients responded to this treatment. In this setting, Janus Kinase inhibitors (JAKi) have emerged as a promising option for SpA treatment. They act on JAK family members regulating many cytokine signaling pathways involved. Clinical trials have shown significant efficacy for the whole spectrum of SpA phenotypes. However, side effects have emerged and questions arise about their safety profile. This review explores the role of JAK-STAT pathway in SpA, focusing on its involvement in cytokine signaling and immune response regulation, its efficacy, and safety of JAKi. Thus, we searched the relevant literature in PubMed and Scopus from January 2016 until January 2025. EXPERT OPINION:JAKi are useful in the treatment of SpA and are recommended by international authorities in patients suffering from SpA. Despite the promising results, ongoing research is essential to assess the benefit-risk profile of JAKi in SpA.

Heart involvement in Systemic Sclerosis (SSc) remains among the leading causes of disease-related deaths. SSc has been associated with an increased risk of pericardial effusion (PerEff). The aim of our study was to examine the prevalence and identify possible factors associated with ever and persistent SSc-PerEff. For this retrospective study, consecutive patients with a diagnosis of SSc, that visited our Outpatient Unit until June 2024, were recruited. Demographic data, disease manifestations, serological profile, and internal organ involvement were collected. Initially, participants with at least one measurement of PerEff were enrolled. For the second step individuals with at least two echocardiograms were included and were classified into three groups: single, persistent and never PerEff. In total 290 adult patients (female-to-male ratio 5.6:1) were included. Results showed that 24.5% of the patients had at least one echocardiogram ever positive for PerEff and 13.2% exhibited persistent PerEff. In the multivariate analysis, ever PerEff was associated with the presence of pulmonary hypertension [PH, Odds ratio, (OR):3.22, p < 0.01], interstitial lung disease (ILD, OR:4.18, p < 0.01), telangiectasias (OR:4.25, p < 0.01) and elevated erythrocyte sedimentation rate (ESR, OR:2.01, p < 0.05). Persistent PerEff was, also, associated with PH (OR:2.90, p < 0.05), ILD (OR:6.65, p < 0.05), telangiectasias (OR:4.84, P < 0.05) and elevated ESR (OR:2.76, p < 0.05). PerEff is a common disease-related manifestation. Both ever and persistent PerEff were associated with PH, ILD, telangiectasias and increased inflammatory markers. The present study further supports the clinical significance of PerEff in SSc patients, with important implications in disease course and management.

Silicone is a chemical compound that is composed of one silicone atom and two atoms of oxygen. It has a variety of clinical applications such as breast and joint implants, intraocular lenses and others. Silicone is associated with a variety of autoimmune/inflammatory syndromes induced adjuvant, called ASIA syndrome, among them is lupus development. A 48year-old woman who had silicone breast implantation bilaterally 4 months earlier, presented to us with abrupt, extensive erythematosus skin manifestations affecting her face, nose and lips. She presented annular lesions affecting the upper back and erythematosus lesions affecting the palms of both hands. She manifested also epidermal necrolysis involving the breasts, areolas and nipples bilaterally. Laboratory evaluation revealed low white blood cells, positive antinuclear antibodies at a titre of 1/320, fine speckled pattern and Ro(SSA) and Smith(Sm) antibodies. The patient satisfied the classification criteria for lupus and the proposed criteria for silicone induced ASIA syndrome. She was treated with prednisone 40mg/day plus hydroxychloroquine 400mg/day with excellent results. Thus, through the above case we review and discuss the relevant literature of silicone induced lupus. This is a unique described case with such extensive and severe skin manifestations induced from silicone. To this end, physicians must be aware and recognise these symptoms and signs of patients exposed to silicone and treat them promptly and appropriately.

The spondyloarthritides (SpA) are a group of chronic inflammatory diseases that affect the axial skeleton (ax-SpA), peripheral joints and entheses (p-SpA) and are expressed with several clinical phenotypes such as psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD), and uveitis. The pathogenesis of SpA involves the pivotal role of tumour necrosis factor alpha (TNFα) and the interleukins (IL) IL-17/IL-23. Their distribution and hierarchy in the affected organs and tissues is differently expressed in SpA. TNFα is expressed in all tissues and organs, while IL-17 and IL-12/IL-23 is lacking from the gut and the axial skeleton respectively. This knowledge is a dilemma for physicians when they must choose a biological therapy. Nowadays, the armamentarium of SpA treatment has been expanded comprising biological therapies such as TNFα inhibitors (TNFαi), IL-17 inhibitors (IL-17i), IL-12/IL-23 inhibitors (IL-12/IL-23i), as well as the Janus Kinase inhibitors (JAKi). Several studies have shown that IL-12/IL-23i are very effective to treat psoriasis, PsA and IBD, but are ineffective in treating ax-SpA. IL-17i are very effective in patients with ax-SpA, psoriasis and PsA, but seem ineffective in IBD. Finally, TNFαi have shown to be effective in all SpA phenotypes with an acceptable toxicity profile. On the other hand, JAKi are also effective in almost all SpA phenotypes, but caution is required for elderly patients who may develop Herpes-Zoster infection, thromboembolic events and malignancies. However, the treatment of SpA is individualised according to the clinical phenotype and after shared decision between patients and physicians.

Background: Systemic Sclerosis (SSc) is a complex connective tissue disease, with multiple organ involvement. The heart is frequently involved and all structures of the heart can be affected. Pericardial effusion (PE), although usually asymptomatic, has been associated with reduced survival in SSc cohorts [1,2]. Most studies, however, have focused on the association of PE with pulmonary hypertension (PH) in SSc, where PE is a prognostic factor for survival among SSc patients with PH [3,4]. Objectives: The aim of our study was to evaluate the frequency and to investigate possible associations of persistent/recurrent PE with clinical and serological characteristics in a cohort of Greek SSc patients. Methods: This is a retrospective study. Patients with a definite diagnosis of SSc, that were followed at our centre, were included in the study. Demographic, clinical and serological characteristics, along with information regarding echocardiograms were recorded. Results: In total 163 SSc patients had at least 2 echocardiograms and were enrolled in the analysis. Median disease duration was 9.1 (4.7 – 15.8) years. Most of the patients were female (84.7%) and 66.9% had limited SSc. Of these patients, 12.9% had persistent/recurrent PE, 18.4% had PE on one echocardiogram and 68.7% were persistently negative for PE. Persistent/recurrent PE was associated with heart rate abnormalities, PH, interstitial lung disease (ILD) and telangiectasias. Patients with persistent/recurrent PE were more often under treatment with immunosuppressants, while a trend was observed regarding the use of steroids. Moreover, patients with persistent/recurrent PE had more frequently increased erythrocyte sedimentation rate. In the multivariate analysis, however, only the associations with PH and ILD remained statistically significant. Conclusion: In this study of SSc patients we observed that the presence of persistent/recurrent PE is significantly associated with PH and ILD, irrespectively of the treatment. The results may help the clinician to better stratify the patients in need for a closer follow-up. However, larger and prospective studies are needed to verify these results. REFERENCES: [1] Simeon CP, Armadans L, Fonollosa V, Solans R, Selva A, Villar M, et al. Mortality and prognostic factors in Spanish patients with systemic sclerosis. Rheumatology (Oxford). 2003;42(1):71–5. [2] Becker M, Graf N, Sauter R, Allanore Y, Curram J, Denton CP, et al. Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis. Ann Rheum Dis. 2019;78(9):1242–8. [3] Lefèvre G, Dauchet L, Hachulla E, Montani D, Sobanski V, Lambert M, et al. Survival and Prognostic Factors in Systemic Sclerosis–Associated Pulmonary Hypertension: A Systematic Review and Meta-Analysis. Arthritis Rheum. 2013;65(9):2412–23. [4] Luo Y, Gordon JK, Xu J, Kolstad KD, Chung L, Steen VD, et al. Prognostic significance of pericardial effusion in systemic sclerosis-associated pulmonary hypertension: analysis from the PHAROS Registry. Rheumatology. 2023; Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Tumor necrosis factor alpha (TNFα) is a pivotal cytokine involved in the pathogenesis of certain inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthropathies, and inflammatory bowel diseases. In the last two decades, TNFα inhibitors (TNFi) have revolutionized the treatment and outcome of the above disorders. However, the use of TNFi has been associated with the development of many autoimmune phenomena and paradoxical skin manifestations that may present as the same type of clinical indications for which the TNFi effectively used. Thus, they may display as arthritis, uveitis, colitis, psoriasis, and several other cutaneous clinical manifestations, among them the development of morphea, a localized scleroderma skin lesion. Case Presentation: We describe a 58-year-old woman with seronegative RA, refractory to methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was discontinued and two months later, she had substantial skin improvement. Conclusion: This is the first report of morphea manifestation during TNFi biosimilar since the patient had no other trigger factors for morphea development like trauma and infections. Physicians dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions, among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow- up check are required.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the peripheral diarthrodial joints symmetrically and also presenting many extra-articular manifestations. Morbidity and mortality in RA patients are higher compared to the general population. Cardiovascular (CV) disease is one of the most common causes of death in these patients. Classical or traditional risk factors for atherosclerosis development occur more frequently in RA patients compared to those without this condition. Studies have showed that RA patients often present comorbidities such as hypertension, dyslipidemia, diabetes mellitus and obesity. However, the high incidence of CV events occurring in RA patients is not explained by the presence of traditional risk factors. Systemic inflammation, as it is expressed with the presence of proinflammatory cytokines and increased acute phase reactants, may contribute to the development of premature atherosclerosis in these patients. In this review, we explore the risk factors for CV disease, the generation of dyslipidemia, the lipid paradox and the role of systemic inflammation in the atherosclerotic process in RA. We discuss also the role of early therapeutic intervention that suppresses inflammation which may have beneficial effects on CV disease in RA patients.

Introduction:Psoriasis is an inflammatory skin disease that in some cases is accompanied by systemic manifestations. Given the varied clinical manifestations, the term psoriatic disease probably better reflects the clinical picture of these patients.Literature review:In most cases, the skin lesions precede joint involvement as well as other potentially involved organs such as the intestine and the eye. Various immune-mediated cellular pathways such as that of TNFα, IL-23, IL-17 as well as other cytokines are involved in the pathophysiology of the psoriatic disease.Future insights:A better understanding of the way they interfere with our immune system has led to remarkably better disease control and outcomes. This review aims to highlight the newest treatments for psoriatic disease, which are expected to significantly reduce unmet needs and treatment gaps.

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease that significantly impacts patients' quality of life. While treatment options have expanded over the years, including the introduction of tumor necrosis factor-alpha (TNF alpha) inhibitors (TNFi), optimizing withdrawal strategies for these agents remains a challenge.Areas coveredThis review examines the current evidence on TNFi withdrawal strategies in RA, focusing on factors influencing withdrawal decisions such as disease activity monitoring, treatment response, patient characteristics, and biomarkers. A comprehensive literature search was conducted, including randomized controlled trials, observational studies, and expert guidelines. The pathophysiology of RA, current pharmacological agents, and the treat-to-target strategy are discussed to provide a holistic understanding of RA management.Expert opinionWithdrawal strategies could be suitable for certain patients, keeping in mind that several factors influence withdrawal decisions, including treatment response, disease activity and monitoring, and patient characteristics. The decision to withdraw TNFi must balance the benefits against the potential risks of disease flare and long-term treatment-related adverse effects. Combining DMARDs and TNFi early improves outcomes, supporting tapering strategies for cost-effectiveness and flare prevention. Future directions, including precision medicine approaches, patient-centered care models, and health economics analyses, are proposed to further optimize RA management and improve patient outcomes.