Search Results (373)

Background/Objectives: Behçet’s disease (BD) is a systemic vasculitis frequently affecting women of childbearing age. However, the relationship between systemic manifestations and pregnancy loss remains unclear. This study evaluated the association between pregnancy loss history and systemic clinical characteristics in women with BD. Methods: This retrospective cohort study included 114 women with BD followed in a rheumatology outpatient clinic between January 2021 and December 2025. In total, 196 pregnancies were recorded. Women without a pregnancy history were excluded. Pregnancy loss was defined as any spontaneous loss, including biochemical pregnancy, miscarriage, or fetal death, excluding elective terminations. Disease activity was assessed using the Krause score, and univariable logistic regression was performed. Results: Among 97 women with a pregnancy history, 25 (25.8%) had at least one pregnancy loss. Compared with women without pregnancy loss, those with pregnancy loss had longer disease duration and higher Krause scores. Gastrointestinal involvement (OR 6.31, 95% CI 1.87–23.28, p = 0.0035) and ocular involvement (OR 3.93, 95% CI 1.44–10.89, p = 0.0076) were significantly associated with pregnancy loss history. Higher Krause scores were also associated with greater odds of pregnancy loss history. Conclusions: In women with BD, pregnancy loss history was associated with systemic organ involvement and higher disease activity, particularly gastrointestinal and ocular involvement. These findings should be interpreted cautiously in light of the retrospective design and univariable analyses, and they suggest that pregnancy loss history may be associated with greater systemic disease burden. Full article

Background and clinical significance: Scurvy, resulting from vitamin C deficiency, is rare in the 21st century, particularly in high-income settings. Its nonspecific presentation and ability to mimic a wide range of conditions make diagnosis incredibly challenging. Pseudovasculitic petechial lesions of the lower limbs may be misdiagnosed as systemic vasculitis, often leading to extensive investigations and delayed treatment. Case presentation: We report the case of a 45-year-old woman who presented with progressive lower limb pain, swelling, and vasculitis-like petechial rash with ecchymoses. Extensive investigations for autoimmune, infectious, malignant, and vascular causes, including skin biopsy, were unremarkable. A detailed dietary history revealed markedly restrictive intake. Characteristic dermatological findings, including perifollicular haemorrhage, ecchymoses and hair shaft abnormalities, raised suspicion for scurvy. Profoundly reduced serum ascorbic acid levels confirmed vitamin C deficiency. Conclusions: This case highlights the importance of thorough dietary assessment, recognition of characteristic cutaneous features, and identification of risk factors such as restrictive eating patterns or chronic gastrointestinal symptoms. It underscores the need for a high index of clinical suspicion for scurvy, even in contemporary high-income settings. Early diagnosis and vitamin C supplementation can result in rapid clinical improvement and prevent avoidable morbidity. Full article

This pharmacovigilance study drew upon the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database to compare the reporting patterns of ocular and systemic adverse events (AEs) for the 2 mg (standard-dose [SD]) and 8 mg (high-dose [HD]) formulations of aflibercept given for any ocular indication. Disproportionality analysis, including reporting odds ratios (ROR), was used to compare each dose individually to the background reporting rate for the AE. Statistical significance of the RORs was evaluated using Bonferroni correction, alongside signal detection based on Evans criteria, and Bayesian information components. The Breslow–Day test was used to conduct a head-to-head comparison of RORs between each dose. We identified 953 SD and 314 HD AE reports within the 750-day period after the approval of HD by the U.S. Food and Drug Administration (FDA; 8/18/2023). Compared to SD, HD had a higher ROR for endophthalmitis (HD: ROR 767.56 [95% CI, 466.11–1263.95]; SD: ROR 331.64 [95% CI, 216.71–507.51]), eye inflammation (HD: ROR 118.45 [95% CI, 55.85–251.20]; SD: 43.98 [95% CI, 21.87–88.44]), retinal vasculitis (HD: ROR 769.87 [95% CI, 337.13–1758.04]; SD: ROR 124.80 [95% CI, 39.67–392.63]), and systemic vasculitis (HD: ROR 28.40 [95% CI, 14.63–55.14]; SD: ROR 4.05 [1.52–10.82]). These results, based on FAERS, indicate associations rather than causal relationships. Further studies are needed to quantify the absolute risks and elucidate the mechanisms underlying differences in safety signals, if any. Full article

Background and Clinical Significance: Left atrial myxoma is the most common benign primary cardiac tumor and is associated with embolic and hemodynamic complications. Complete surgical excision is the treatment of choice, while postoperative cardiovascular rehabilitation is essential for functional recovery. Case Presentation: We report the case of a 75-year-old woman with arterial hypertension, dyslipidemia, and chronic venous insufficiency (Clinical–Etiological–Anatomical–Pathophysiological (CEAP) class 2), and chronic hepatitis B virus (HBV) infection who underwent surgical excision of a left atrial myxoma and was subsequently admitted three weeks postoperatively for phase II cardiovascular rehabilitation. The postoperative course was complicated by transient atrial fibrillation, peripheral edema, pleural effusion, and progressive purpuric lesions of the lower limbs. Laboratory and immunological evaluation revealed positive cryoglobulins, markedly elevated rheumatoid factor (1058 UI/mL) and IgM levels (715 mg/dL), reduced complement levels (C3, C4), normocytic normochromic anemia, microscopic hematuria, and elevated ALT (156 U/L), AST (142 U/L), total bilirubin (1.4 mg/dL), and INR (1.6), suggestive of hepatic inflammatory activity. HBV status was scheduled for evaluation through Gastroenterology referral (HBV DNA viral load, serological markers: HBsAg, HBeAg, anti-HBe), as our Cardiology Rehabilitation Clinic lacks the possibility of evaluation. After systematic exclusion of alternative etiologies, secondary cryoglobulinemic vasculitis in the context of chronic HBV infection with biochemical evidence of hepatic activity was considered the most plausible diagnosis. Conclusions: This case highlights the complexity of managing elderly patients after cardiac tumor surgery, particularly in the presence of systemic comorbidities. Early recognition of extracardiac complications and an individualized, multidisciplinary strategy are essential to optimize outcomes. Full article

Background: Kawasaki disease (KD) is a systemic vasculitis of unknown origin, though recent evidence implicates viral pathogens in its pathogenesis. Given the central role of T cell receptors (TCRs) in antigen recognition and immune response, this study investigated the association between KD and viral infection through comparative analysis of TCR repertoires. Methods: TCR repertoires from KD patients, healthy children, and individuals with viral infections were comparatively analyzed. TCR diversity and V(D)J usage were assessed using Shannon’s entropy, the Mann–Whitney U test, and Fisher’s exact test. Positional motif enrichment analysis within CDR3 regions was performed based on paratope hotspot classification. Results: Relatively reduced TCR clonal abundance and diversity were observed in KD patients compared to healthy controls. While substantial overlap in VJ gene segment usage was detected between KD and cytomegalovirus (CMV) infection, limited overlap in clonal TCRαβ chains was found between KD and viral infection groups. A predominant TCR combination, TRAV14DV4-J13-TRBV20-1-J2-5, enriched with characteristic amino acid motifs (EET, YNE, LAG, GQG, and AYE), was frequently identified in KD. Conclusions: These observations suggest potential differences in TCR repertoire features between KD patients and both healthy and virus-infected groups. However, the relationship between KD pathogenesis and the viruses examined requires further investigation with larger cohorts. Full article

Objective: To evaluate the diagnostic yield and clinical impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with unexplained inflammation, fever, or suspected malignancy, and to assess its role across different rheumatologic subgroups. Methods: We retrospectively analyzed 280 patients who underwent PET/CT between 2010 and 2020 in a tertiary rheumatology center. Demographic, clinical, and laboratory data including erythrocyte sedimentation rate, C-reactive protein, and PET/CT indications were collected. PET/CT findings were categorized as inflammatory, neoplastic, or normal based on visual assessment and SUVmax. Final diagnoses were confirmed using clinical, histopathological, or follow-up data. Statistical analysis compared PET/CT results, inflammatory markers, and diagnostic outcomes among disease subgroups. Results: Of 280 patients (mean age 58 ± 15 years, 63.9% female), 72% had an established rheumatologic diagnosis prior to PET/CT. A new diagnosis, confirmed by predefined clinical, histopathological, or follow-up criteria, was established in 29.6% of patients, predominantly among those undergoing diagnostic evaluation for unexplained inflammation, including 40 rheumatologic and 43 non-rheumatologic conditions (22 malignancies). PET/CT led to therapeutic modification in 27.1% of all cases, based on multidisciplinary clinical decision-making. PET/CT demonstrated the highest diagnostic contribution in vasculitis, IgG4-related disease, and sarcoidosis. Median SUVmax was higher in malignancies than in inflammatory diseases [8.0 vs. 4.6, p < 0.05]. Lymphadenopathy was more frequent in non-rheumatologic and malignant conditions (p = 0.002). PET/CT findings showed variable but clinically relevant concordance with other imaging modalities. Conclusions: PET/CT provides supportive diagnostic and management insights in complex or atypical rheumatologic presentations. It demonstrated high yield in systemic inflammatory disorders and providing supportive information for malignancy exclusion in connective tissue diseases when interpreted alongside clinical and laboratory follow-up. Integration of PET/CT with clinical and laboratory data enhances diagnostic accuracy and supports patient-centered management in rheumatology. Full article

Background: Raynaud’s phenomenon of the tongue is a rare manifestation that may be associated with systemic diseases. The clinical manifestations, etiologies and management of this condition are poorly described. Methods: We report 10 cases of lingual Raynaud’s phenomenon (LRP) and 26 cases from a structured literature review. Results: In 38.8% of cases, the LRP occurred in the context of a previously diagnosed systemic sclerosis; 16.6% followed radiotherapy for head and neck cancer; and 27.8% of patients presented with an idiopathic-like form. The manifestations classically included a syncopal phase (91.7%) associated with hypoesthesia (88.9%) and possible dysarthria (52.8%). Atypical presentations with a primary cyanotic phase were also observed, particularly in the context of vasculitis, notably cryoglobulinemic vasculitis (four patients). Active smoking was a significant triggering factor in idiopathic forms (60%). Across all patients—both primary and secondary forms—the most common triggering factor was cold exposure (75%). Vasodilator use showed good efficacy and should be considered for all highly symptomatic patients. Conclusions: In summary, LRP is more frequently associated with systemic sclerosis, manifesting as blanching of the tongue associated with hypoesthesia and dysarthria in more than half of cases. Vasodilators may reduce symptoms. Larger studies are needed to confirm these findings. Full article

Urticaria is a mast cell-mediated disorder commonly encountered in women of reproductive age, making its interaction with pregnancy clinically relevant. Gestation induces profound hormonal and immunologic adaptations—including shifts between Th1/Th17 and Th2/Treg responses and sustained exposure to sex steroids and placental hormones—that can modulate mast cell reactivity. As a result, chronic urticaria (CU) shows heterogeneous behavior during pregnancy: approximately half of patients improve, one third worsen, and the remainder remain stable. Pregnancy also presents several urticaria-like dermatoses, notably polymorphic eruption of pregnancy (PEP/PUPPP), atopic eruption of pregnancy (AEP) and pemphigoid gestationis (PG), as well as rare hormone-induced hypersensitivity reactions. Additionally, systemic disorders such as intrahepatic cholestasis of pregnancy (ICP), chronic kidney disease–associated pruritus and urticarial vasculitis may mimic urticaria but differ markedly in prognosis, maternal–fetal risk and management. Given this complexity, accurate diagnosis requires integration of temporal pattern, lesion morphology and duration, distribution, systemic features and targeted investigations, as outlined in the diagnostic algorithm proposed. Most pregnancy-specific eruptions are benign, whereas PG, ICP and urticarial vasculitis warrant prompt recognition due to potential fetal implications. Management of CU in pregnancy generally follows standard guidelines, with second-generation H1-antihistamines as first-line therapy and omalizumab reserved for severe refractory cases. Full article

Purpose: Kawasaki disease (KD) is an acute systemic vasculitis that can result in coronary artery lesions (CALs). This study aims to explore the expression levels of serum Ninjurin-1 (NINJ1) and high-mobility group box 1 (HMGB1) in the acute phase of KD and evaluate their clinical significance. Methods: A total of 180 children were enrolled, comprising 113 KD patients, 35 healthy controls (HCs), and 32 febrile controls whose clinical data were collected. Serum levels of NINJ1, HMGB1, Lactate Dehydrogenase (LDH), and routine inflammatory markers were compared across groups. Serum levels of NINJ1 and HMGB1 were measured via ELISA. Correlations were analyzed using Spearman tests. The diagnostic and predictive performance of biomarkers was assessed using Receiver Operating Characteristic (ROC) curve analyses. Results: Serum levels of NINJ1 and HMGB1 were significantly elevated in the KD group compared with both the HC and FC groups (all p < 0.001). NINJ1 levels were positively correlated with the z-scores of coronary arteries and were significantly higher in the CAL subgroup than in the non-CAL subgroup (p = 0.004). A strong positive correlation was observed between serum NINJ1 and HMGB1 levels in the KD group (p < 0.001). Conclusions: Elevated serum NINJ1 levels during the acute phase of KD were associated with the presence of CALs, while HMGB1 shows promise in differentiating KD from other febrile illnesses. These findings collectively suggest that the NINJ1-HMGB1 axis may offer novel insights into the mechanisms underlying KD vasculitis, supporting further investigation into its potential clinical relevance. Full article

Peripheral ulcerative keratitis (PUK) is a sight-threatening corneal disorder characterized by progressive peripheral stromal thinning and ulceration. It often reflects an underlying systemic autoimmune or vasculitic disease and may herald severe morbidity or even mortality. This review offers a comprehensive synthesis of current knowledge on the pathophysiology, clinical presentation, diagnostic approach, and management strategies for PUK, with a special focus on idiopathic forms such as Mooren’s ulcer. We explore the immunological mechanisms driving peripheral corneal destruction, including the roles of complement activation, matrix metalloproteinases, and systemic immune dysregulation. A detailed classification of etiologies, including systemic autoimmune diseases, infectious causes, and iatrogenic forms, is presented, along with recommendations for diagnosis, laboratory workup, and differential diagnosis. Management strategies are reviewed in a stepladder approach, from local anti-collagenase and immunomodulatory therapy to systemic immunosuppressants and biologics, and, when necessary, surgical intervention. Full article

Background: Pancreatic involvement in Kawasaki disease (KD) is rare. Case presentation: A 13-year-old adolescent presented with severe epigastric pain, elevated pancreatic enzyme levels, and conjunctival injection, but he lacked a fever and the other classic features of KD. The patient was initially diagnosed with acute pancreatitis and treated conservatively. As his abdominal pain improved, mucocutaneous findings emerged, leading to a diagnosis of complete KD. A literature review was conducted to summarize reported cases of KD-associated pancreatitis. This review highlights the older age of affected patients, the variability in the timing of pancreatitis onset, and a tendency toward delayed diagnosis. Conclusions: Pancreatic involvement, including pancreatitis, can occur before typical mucocutaneous features and should be considered in older children and adolescents presenting with unexplained abdominal pain and pancreatic enzyme elevation. Increased awareness of this atypical presentation may help reduce diagnostic delay and support timely management. Full article

Background: Superficial venous thrombosis (SVT) is an inflammatory and thrombotic disorder affecting superficial veins. While varicose veins (VVs) are the primary risk factor, SVT occurring in non-varicose veins (NVVs) is a critical clinical finding, often acting as a sentinel marker for severe systemic pathologies. Aims: This review aims at examining incidence, mechanisms, underlying causes, and clinical outcomes of SVT within the NVV population. Materials and Methods: We conducted a comprehensive narrative review of the existing medical literature. Results: SVT in NVVs is frequently associated with systemic conditions, including inherited or acquired thrombophilia, visceral or hematologic malignancies (notably Trousseau’s syndrome), vasculitis (e.g., Behçet’s syndrome), and connective tissue disorders. Specific manifestations like migratory SVT or Mondor’s disease provide crucial diagnostic clues. Notably, NVV-SVT carries a significantly higher risk of recurrence and venous thromboembolic events compared to VV-associated cases. Conclusions: A thorough diagnostic work-up is essential for patients with NVV-SVT to ensure early detection of underlying systemic diseases. Although current management does not differentiate between VV and NVV cases, the increased thromboembolic risk in the latter suggests a need for tailored therapeutic approaches. Further prospective studies are required to evaluate differentiated anticoagulant strategies regarding dosage and duration for this high-risk population. Full article

Factor XII is a molecule of unclear physiological function that has attracted increasing research interest across multiple medical disciplines. In recent years, a substantial body of evidence has emerged regarding the contribution of factor XII to the pathogenesis of inflammatory and prothrombotic conditions. FXII has been shown to play a protective role in FXII-driven coagulation during host defence against infections and to protect against multi-organ failure in animal models of sepsis. In acute respiratory distress syndrome (ARDS), FXII activity contributes to the release of pro-inflammatory mediators and is associated with severe clinical outcomes; it also induces fibroblast migration in idiopathic pulmonary fibrosis. FXII deficiency has been associated with reduced neutrophil adhesion and migration in sterile skin wounds and immune complex-induced vasculitis. In neurological conditions, FXII deficiency significantly reduced the number and severity of multiple sclerosis relapses and decreased the volume of post-traumatic brain oedema. In heart failure pathogenesis, FXII deficiency and pharmacological inhibition of FXII activity blocked activation of the renin–angiotensin–aldosterone system (RAAS) in dilated cardiomyopathy, increased median survival, and delayed heart failure onset in murine models. Importantly, FXII inhibition prevented arterial thrombosis without affecting haemostasis. This review summarises the latest findings on the contribution of FXII to inflammatory and prothrombotic states across multiple medical fields, including cardiology. Pharmacological inhibition of FXII has generated considerable interest as a potential future therapeutic strategy; however, to date, human studies remain limited. Full article

Background: Cardiovascular implications in systemic lupus erythematosus (SLE) are common and varied, including impacts on the pericardium, myocardium, valves, coronary arteries, and conduction system; all of these could be potential substrates or triggers of cardiac arrhythmias by interfering with disease severity and specific medication. Therefore, this narrative review aimed to assess the cardiac involvement in SLE underlying, mainly, cardiac arrhythmias. Methods: We analyzed studies, published between 2015 and 2025 on PubMed, which explore cardiovascular involvement with a focus on arrhythmias in SLE from the perspectives of epidemiology, underlying mechanisms, diagnostic techniques, and the impact of standard and biologic therapies. Results: The cardiac manifestation of LES (lupus pericarditis, lupus myocarditis, Libman–Sacks endocarditis, coronary artery disease, coronary vasculitis or myocardial fibrosis) represents a substrate for arrhythmia risk. These substrates, in association with other arrhythmias mechanisms considered as triggers or conduction abnormalities, determined arrhythmogenic conditions in these patients. In addition to structural heart disease, arrhythmias in SLE are caused by ongoing inflammation, immune system irregularities, microvascular problems, autonomic imbalance, oxidative stress, and side effects from treatments. Despite this complex background, arrhythmias are often overlooked and not routinely investigated in SLE care. Data that show how disease-modifying drugs may affect arrhythmias are limited and inconsistent, highlighting significant gaps in knowledge. Cardiac arrhythmias are a significant but, as yet, insufficiently underrecognized aspect of SLE, with serious implications for prognosis. Conclusions: Systemic lupus erythematosus causes cardiovascular involvement that is associated with arrhythmias through various and complexes mechanisms, mainly related to direct cardiovascular structural damage, systemic inflammation or specific therapies. Data on arrhythmias secondary to cardiovascular damage in patients with SLE in the literature are limited. Therefore, early detection of electrical issues, regular cardiovascular evaluation in high-risk patients, and careful management of treatment effects are vital. A coordinated, multidisciplinary cardio-rheumatology approach is essential to improving arrhythmia detection, tailoring treatments, and ultimately decreasing cardiovascular complications and deaths in SLE patients. Full article

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis that often affects the respiratory tract and kidneys, while ocular involvement is less common and may delay diagnosis. Bilateral dacryoadenitis as an initial manifestation is particularly uncommon and can obscure early recognition. Case Presentation: A 24-year-old woman presented with recurrent epistaxis, headaches, and progressive bilateral eyelid swelling. MRI showed enlarged lacrimal glands consistent with granulomatous dacryoadenitis. Over the following weeks, she developed systemic symptoms and rapidly progressive renal impairment. Serology revealed positive c-ANCA and anti-PR3 antibodies, and HRCT demonstrated pulmonary nodules and ground-glass opacities. Renal biopsy confirmed necrotizing pauci-immune crescentic glomerulonephritis. Despite treatment with glucocorticoids, cyclophosphamide, and rituximab, renal recovery was incomplete, necessitating hemodialysis. Conclusions: This case illustrates bilateral dacryoadenitis as an early sign of GPA and emphasizes the need for prompt ANCA testing and renal evaluation. Early recognition is crucial to prevent irreversible kidney damage. Full article