Search Results (69)

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), represent a spectrum of systemic disorders characterized by necrotizing inflammation of small- to medium-sized vessels. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive technique routinely employed in the assessment of microvascular involvement in systemic sclerosis and in the differential diagnosis of Raynaud’s phenomenon; its application in the context of AAV, particularly EGPA, has not been investigated yet. The present study aims to assess the presence and the possible pattern of microcirculatory abnormalities detected by NVC in EGPA patients, and to explore potential correlations between capillaroscopic findings and disease activity status. Methods: A total of 29 patients with EGPA (19 women and 10 men), aged between 51 and 73 years, and 29 age- and sex-matched healthy controls were retrospectively enrolled between October 2023 and April 2025, after providing informed consent and meeting the inclusion and exclusion criteria. NVC was conducted in both groups to assess various morphological parameters, and mean capillary density was also calculated. Results: This study observed the presence of capillaroscopic alterations in the EGPA group, including decreased capillary density (38%), neoangiogenesis (72%), rolling (100%), pericapillary stippling (66%), and inverted capillary apex (52%). Overall, when comparing healthy controls with EGPA patients, microcirculatory abnormalities were significantly more prevalent in the latter. Specifically, scores for neoangiogenesis, capillary rolling, pericapillary stippling, and inverted capillary apex showed p-values < 0.001. Conclusions: Our study demonstrates a higher prevalence of four nailfold videocapillaroscopic abnormalities in patients with EGPA compared to healthy controls. However, the identification of these capillaroscopic alterations as specific to EGPA requires further confirmation. Ongoing studies aim to explore the potential role of NVC as a diagnostic marker and to investigate its correlation with the clinical manifestations of EGPA. Full article

Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article

Background: Antiphospholipid syndrome (APS) is one of the highest risk factors for obstetric complications. This article contains a case report of a patient with obstetric APS who experienced fetal loss during their first pregnancy and experienced a successful second pregnancy upon treatment with acetylsalicylic acid (ASA), low-molecular-weight heparin (LMWH), and hydroxychloroquine (HCQ). We compare placental pathology in these two pregnancies and discuss the impact of antiphospholipid antibodies and clinical management on pregnancy outcomes. We also propose methods to monitor obstetric antiphospholipid syndrome (OAPS) patients during pregnancy. Methods: A 26-year-old woman presented with a history of stillbirth at 25 weeks of pregnancy due to placental insufficiency. Before pregnancy, she experienced symptoms suggestive of autoimmune disease (thrombocytopenia, recurrent mouth aphthous ulcers, and Raynaud’s phenomenon) but had no diagnosis. Placental dysfunction correlated with the high ratio of sFlt-1/PIGF (soluble fms-like tyrosine kinase 1 and the placental growth factors index). Laboratory tests revealed the presence of antinuclear antibodies (ANAs) and triple positivity for antiphospholipid antibodies (aPLs). Results: Following the initiation of treatment for OAPS and regular monitoring consistent with current guidelines, the patient conceived and successfully delivered a healthy child. Conclusions: Adequate therapy and close monitoring during pregnancy, including clinical observation, placental biomarkers and regular ultrasonography, may help to reduce the risks and increase chances for optimal pregnancy outcomes. Additionally, pathological examination and clinical collaboration are essential components in future pregnancy counseling and should be a part of multidisciplinary management. Full article

Systemic sclerosis (SSc) is a heterogeneous disease characterized by vascular alterations, immune dysregulation, and fibrosis. Solid evidence supports the hypothesis that endothelial dysfunction is the key player in SSc vascular injury and a critical factor concurring to the initiation of SSc pathogenesis. This narrative review reports on persistent endothelial dysfunction, resulting from oxidative stress, autoimmunity, and impaired vascular repair, in the course of SSc, and how it can trigger and sustain fibrotic remodeling of various organs. In this paper, we also analyze the impact on SSc of impaired angiogenesis and vasculogenesis, diminished endothelial progenitor cell function, and endothelial-to-mesenchymal transition, which can collectively disrupt vascular homeostasis and promote myofibroblast activation. These pathologic events underlie the hallmark clinical manifestations, i.e., Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. The review highlights how recognizing SSc as a paradigm of systemic endothelial dysfunction may reframe our understanding of its physiopathology, modify current therapeutic strategies, and unveil new therapeutic targets. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Pulmonary arterial hypertension (PAH) is a severe complication associated with connective tissue diseases (CTDs), which is characterized by a significant influence on the patient’s prognosis and mortality. The prevalence of PAH varies depending on the type of CTD. Still, it is highly prevalent in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and primary Sjögren’s syndrome (pSS). Identifying rheumatic disease-specific risk factors is crucial for early diagnosis and intervention. Risk factors for PAH development include specific sociological factors (related to race, gender, and age), clinical features (particularly severe Raynaud’s phenomenon and multiple telangiectasias), cardiological factors (pericarditis and left heart disease), biochemical factors (elevated NT-proBNP and decreased HDL-cholesterol), serological factors (presence of ANA, e.g., anti-U1-RNP or SSA, and antiphospholipid antibodies), and pulmonary factors (interstitial lung disease and decreased DLCO or DLCO/alveolar volume ratio < 70%, FVC/DLCO > 1.6). The analysis of risk factors can be the most useful during the selection of patients at high risk of PAH development. The initial diagnosis of PAH is usually based on transthoracic echocardiography (TTE) and is finally confirmed by right heart catheterization (RHC). Targeted therapies can improve outcomes and include endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase inhibitors, and tailored immunosuppressive treatments. Effective management strategies require a multidisciplinary approach involving rheumatologists, cardiologists, and pulmonologists. The risk stratification and individualized treatment strategies can enhance survival and quality of life in patients with PAH-CTD. Full article

Background and Objectives: Pediatric Sjögren’s syndrome is a rare autoimmune disease with a heterogeneous clinical expression and limited pediatric-specific diagnostic criteria. Ocular involvement often represents an early manifestation, yet it may go unrecognized in children due to poor symptom reporting and the underuse of objective diagnostic tools. This retrospective study evaluated six pediatric patients with Sjögren’s syndrome, integrating systemic and ocular findings with a focus on early immunological and clinical markers. Materials and Methods: All patients underwent ophthalmological assessments, including tear break-up time, Schirmer’s test, and slit-lamp examination. Results: Tear break-up time values consistently indicated tear film instability (mean RE 7.4 ± 2.5 s; LE 7.7 ± 2.3 s), while Schirmer’s test showed greater variability. Slit-lamp examination revealed inhomogeneous tear films in all patients and blepharitis in 66.7%, consistent with Meibomian gland dysfunction. Systemic features included arthralgia, Raynaud’s phenomenon, fatigue, and frequent seropositivity for ANA and anti-SSA/Ro antibodies. Minor salivary gland biopsy confirmed lymphoepithelial sialadenitis in all cases. Conclusions: These findings highlight the importance of combining laboratory and clinical markers with ophthalmological parameters to support an early diagnosis of Sjögren’s syndrome in pediatric patients. Integrating TBUT and slit-lamp evaluation with serological and histopathological data may enhance diagnostic accuracy and guide timely, targeted intervention to prevent long-term complications. Full article

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence and heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The disease progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, to systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, and kidneys. There have been considerable advancements in understanding the pathophysiology of the disease during the last few years and this has already resulted in the improvement of the therapeutic approaches used to control organ-specific manifestations. However, the underlying cause of the disease still remains incompletely elucidated. Methods: Here, we summarize the current knowledge on the SSc pathogenesis. Results: The pathophysiology involves an interplay of chronic inflammation, impaired vascular function, and excessive extracellular matrix deposition, leading to progressive organ damage. Endothelial dysfunction in SSc is driven by immune-mediated injury, oxidative stress, and the imbalance of vasoconstrictors and vasodilators, leading to capillary loss and chronic hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis and impair angiogenesis, further exacerbating vascular damage. Despite increased angiogenic factor levels, capillary repair mechanisms are defective, resulting in progressive ischemic damage. Dysregulated immune responses involving Th2 cytokines, B cells, and macrophages contribute to fibroblast activation and excessive collagen deposition. Transforming growth factor-beta (TGF-β) plays a central role in fibrotic progression, while fibroblasts resist apoptosis, perpetuating tissue scarring. The extracellular matrix in SSc is abnormally stiff, reinforcing fibroblast activation and creating a self-perpetuating fibrotic cycle. Conclusions: Advances in molecular and cellular understanding have facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus on precision medicine approaches, integrating biomarkers and novel therapeutics to improve patient outcomes. Full article

Background/Objectives: Rapid skin thickness progression assessed using the modified Rodnan skin score (mRSS) is associated with poor outcomes in systemic sclerosis (SSc). However, the correlation between patterns of skin thickness and the onset of internal organ involvement remains unclear. This study aimed to determine the correlation between peak skin thickness progression rate (pSTPR) and the onset of internal organ involvement, particularly interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) among Thai SSc patients. Method: A prospective cohort study with retrospective analysis was conducted on adult SSc patients who experienced the onset of their first non-Raynaud phenomenon symptoms between January 2013 and December 2020 and had at least a 2-year follow-up. Patients with an overlap syndrome were excluded from this study. The pSTPR was calculated by dividing the peak of the mRSS by the duration of disease at the peak of the mRSS. Result: A total of 509 patients were included in this study. The majority of cases were female (351; 69.0%) and comprised diffuse cutaneous SSc subsets (353 cases; 69.4%). The respective mean age and median pSTPR was 48.2 ± 11.6 years and 1.63 points/year (interquartile range 0.5–4.4). The respective median durations of disease at the onset of significant ILD (>20% extent), ILD, and mean duration of disease at the onset of PAH were 3.4 (Q1–Q3 1.4–7.7), 5.4 (Q1–Q3 2.4–9.2), and 8.0 ± 4.9 years. pSTPR was negatively correlated with disease duration at the onset of significant ILD (Rho −0.509, p < 0.001), ILD (Rho −0.480, p < 0.001), PAH (Rho −0.372, p = 0.03), and disease duration from onset to death (Rho −0.367, p = 0.03) after adjusting for age, sex, and anti-topoisomerase I. Conclusion: SSc patients with a high skin thickness progression rate reaching the maximum point of mRSS were at risk of developing early ILD, PAH, and death. The pSTPR may be used to assess individuals at risk of experiencing early onset cardiopulmonary involvement in SSc. Full article

Background/Objectives: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis or obstetric complications and the laboratory detection of antiphospholipid antibodies. Although vascular thrombosis is the main manifestation of the disease, other rarer complications have also been described. Avascular necrosis (AN) is considered a rare manifestation of APS. The aim of our case series is to study patients with APS and AN. Methods: A retrospective study was performed on 80 patients diagnosed with APS. Results: AN was observed in 3 patients out of 80 diagnosed with APS. AN of the femoral head was observed in all cases. Case (1): A 54-year-old woman presented due to multiple ischemic infarctions in the brain, as detected in magnetic resonance imaging of the brain, Raynaud’s phenomenon, and AN of the femoral head. In laboratory testing, a prolongation of activated partial thromboplastin time was recorded. A heterozygous mutation was also found in the gene MTHFR C677T, and the patients was positive for lupus anticoagulant (LA). The patient was given clopidogrel and acenocoumarol. Case (2): A 52-year-old man was diagnosed with APS, based on the clinical presentation (stroke) and positivity for LA and anti-β2GPI (anti-β2 glycoprotein I antibody). In his medical history, episodes of vertigo and an episode of AN of the femoral head 2 years ago were described. Case (3): A woman aged 43 years presented due to AN of the femoral head. Due to suspected APS, immunological testing was performed, and positivity for LA and IgM anticardiolipin antibodies was detected. She was treated with acenocoumarol. Conclusions: AN is a rare clinical manifestation of APS, which may precede the diagnosis of APS for many years. Full article

Interstitial lung disease (ILD) is a severe complication of certain connective tissue diseases (CTDs) such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), idiopathic inflammatory myopathies (IIM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and it is associated with nailfold videocapillaroscopy (NVC) changes and increased morbidity and mortality rates. Early diagnosis is crucial in order to prevent the progression of ILD, prevent respiratory failure and enhance the patient’s overall quality of life. The most common paraclinical investigations are high-resolution computed tomography (HRCT) and functional respiratory tests such as forced vital capacity (FVC) and the diffusing capacity of the lungs for carbon monoxide (DLCO). The most frequent CTD associated with both ILD and NVC changes is systemic sclerosis. The “late” scleroderma pattern was the most common abnormality identified in NVC results in SSc patients. Other autoimmune diseases were also correlated with ILD and NVC changes, especially when the Raynaud phenomenon was present. Low capillary density was associated with the presence and severity of ILD and a reduction in FVC and DLCO. NVC can also differentiate the capillaroscopic changes in some particular types of ILD, such as the usual interstitial pneumonia (UIP) pattern from the non-specific interstitial pneumonia (NSIP) pattern. Nevertheless, further extensive research is necessary in order to establish the diagnostic value of NVC in CTD-ILD in clinical practice. Full article

Background: Aminaphtone is a well-established pharmaceutical agent that has been utilized for over 40 years, primarily due to its effectiveness in treating microvascular disorders. Recent studies have explored its impact on various conditions, including chronic venous insufficiency, diabetic microangiopathy, leg ulcers, systemic sclerosis, and Raynaud’s phenomenon. These investigations have consistently demonstrated that aminaphtone enhances skin blood perfusion and mitigates endothelial damage, all while maintaining a robust safety profile over time. Case Summary: This report highlights the potential of aminaphtone in improving microcirculation in a young patient who experienced spontaneous capillary rupture in her second finger. A 38-year-old woman with undifferentiated connective tissue disease presented to the clinic for periungual videocapillaroscopy (NVC). Given the microangiopathic changes observed during the NVC, she was prescribed aminaphtone. After seven months of treatment, a follow-up NVC revealed significant improvement in the capillaroscopic findings. A comprehensive literature review on aminaphtone was conducted using electronic databases (PUBMED, Google Scholar, ResearchGate, UpToDate), along with manual searches, focusing on articles published until November 2024. Conclusion: Treatment with aminaphtone led to notable improvements in microangiopathic health. Following the introduction of this medication, the nailfold microvascular bed, which previously exhibited severe alterations, showed a remarkable transition to only mild abnormalities. Full article

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. Full article

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. Full article

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. Full article