Exploring the Labyrinth: Imaging in Systemic Vasculitis.

Systemic vasculitis is an immune-mediated group of disorders broadly classified based on the involved vessel type. It has myriad clinical presentations, adding to the challenge of timely diagnosis and management. Thus, imaging has taken center stage in the diagnosis of these disorders as there is a lack of definitive clinical diagnostic markers. Various available imaging modalities can be used for diagnosis and follow-up on these patients. The coronavirus disease 2019 (COVID-19) has added a new dimension to the already existing problem of vasculitis. The virus has shown great affinity for the vascular endothelium, leading to multisystem organ vasculitis. There has been a spike in vasculitis cases in the COVID-19 pandemic era, thus necessitating more research and studies in this field for a better understanding of the disease. In this review, we wish to summarize the various imaging spectrums of classical systemic vasculitis along with the new addition of COVID-19-related vasculitis to the already long list.

Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis.

OBJECTIVES: Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. METHODS: We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. RESULTS: We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. CONCLUSION: Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

Systemic vasculitis involving the kidney: the nephropathologist's point of view.

Kidneys are often targets of systemic vasculitis (SVs), being affected in many different forms and representing a possible sentinel of an underlying multi-organ condition. Renal biopsy still remains the gold standard for the identification, characterization and classification of these diseases, solving complex differential diagnosis thanks to the combined application of light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). Due to the progressively increasing complexity of renal vasculitis classification systems (e.g. pauci-immune vs immune complex related forms), a clinico-pathological approach is mandatory and adequate technical and interpretative expertise in nephropathology is required to ensure the best standard of care for our patients. In this complex background, the present review aims at summarising the current knowledge and challenges in the world of renal vasculitis, unveiling the potential role of the introduction of digital pathology in this setting, from the creation of hub-spoke networks to the future application of artificial intelligence (AI) tools to aid in the diagnostic and scoring/classification process.

Diagnostic delays in systemic vasculitides.

Systemic vasculitides are among the less common disorders encountered in routine rheumatology practice. The low incidence and heterogeneous presentation at onset can potentially lead to delayed diagnosis. Not recognizing these in the early phase may prove detrimental, as some vasculitis may progress to a catastrophic course with major morbidity or mortality. The causes of diagnostic delay may vary among different types of vasculitis and may also be disease-, patient-, or physician-related. Disease-related factors include the myriad presentations with diverse and non-specific symptoms, mimicking other conditions like infections. In addition, some forms have prolonged prodromal phases before evident organ damage. Limited awareness among healthcare professionals, particularly outside rheumatology, and a lack of readily available diagnostic tools contribute to missed diagnoses. Delays in seeking care due to non-specific symptoms or lack of access to specialist care can worsen outcomes. The economic burden also increases with delayed diagnosis and damage accrual when the disease remains unrecognized or untreated for prolonged periods. Although the causes of vasculitis are numerous, including secondary causes, in this review, we focus on diagnostic delays in primary vasculitides and suggest potential steps to identify and treat these diseases early. These include educating both healthcare professionals and the public about the signs and symptoms of vasculitis; expanding the rheumatology workforce and facilitating timely referrals; implementing readily available and reliable tests for early detection; and streamlining care and diagnostic pathways. Such measures have the potential to improve the overall outcomes of the disease, with prolonged remission, minimal damage accrual, and improved quality of life.

Systemic vasculitis: one year in review 2024.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Patient-reported outcomes in vasculitis.

Systemic vasculitis encompasses a group of multisystem disorders; both the diseases and the treatment strategies can have a significant impact on a patient's health-related quality of life (HRQoL). Using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) to evaluate the patient's view of their condition, treatments, and healthcare journey is essential to the patient-centered care approach. In this paper, we discuss the use of generic, disease-specific, and treatment-specific PROMs and PREMs in systemic vasculitis and future research goals.

Systemic vasculitis: one year in review 2023.

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS / Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome

A finales de 2020 se describió el síndrome VEXAS, como una enfermedad autoinflamatoria causada por variantes poscigóticas en el gen UBA1. Se presenta en varones adultos con fiebre recurrente, artralgias/artritis, condritis auricular/nasal, dermatosis neutrofílica, inflamación pulmonar, trombosis venosas y diferentes tipos de vasculitis. Los análisis muestran una respuesta de fase aguda elevada y anemia macrocítica. Es frecuente la coexistencia de mielodisplasia, y son características las vacuolas citoplasmáticas en precursores mieloides y eritroides en médula ósea. Los glucocorticoides a dosis medias-altas son eficaces, pero el resto de fármacos inmunodepresores, convencionales o biológicos, muestran una eficacia limitada o ausente. Azacitidina se ha asociado con una buena respuesta, sobre todo en pacientes con síndrome mielodisplásico acompañante. El trasplante alogénico de progenitores hematopoyéticos parece ser la única terapia curativa hasta el momento. El síndrome VEXAS ha supuesto un cambio de paradigma en el diagnóstico y tratamiento de las enfermedades autoinflamatorias y las vasculitis sistémicas. (AU)

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis. (AU)

Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome. / Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS.

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis.

Predictive Factors of Severe Behçet's disease: A Longitudinal, Prospective Cohort Followed Between 1981–2020 / Factores predictivos de la enfermedad de Behçet grave: una cohorte prospectiva longitudinal seguida entre 1981-2020

Introduction: Behçet's disease (BD) is a systemic vasculitis of unknown cause. The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity. Associations between disease severity and male sex, earlier age at onset, and the presence of erythema nodosum have been described. Objectives: To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort. Methods: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020. Severe BD was defined as a Krause total clinical severity score >4 points. Results: We included 243 patients, of whom 31% were male, with an average follow-up time of 14.6 years. Regarding organ manifestations, all patients had mucous manifestations (N=243, 100%), 133 (55%) skin, 104 (43%) joint, 71 (29%) ocular, 48 (20%) vascular, 47 (19%) neurological, 22 (9%) gastrointestinal and 1 (0.4%) cardiac involvement by BD. One hundred fifty-six (64%) patients were classified as having severe BD. Severe BD was more frequent in men (OR=2.004, p=0.024), increasing with age (OR=1.021 per year, p=0.037), in the presence of skin manifestations (OR=4.711, p<0.001), specifically erythema nodosum (OR=8.381, p<0.001), and pseudofolliculitis (OR=2.910, p<0.001). In the multivariate model, variables independently associated with severe BD were male gender (Adjusted OR=1.961, p=0.047), erythema nodosum (Adjusted OR=8.561, p<0.001) and pseudofolliculitis (Adjusted OR=2.372, p=0.007).Discussion: Male gender, erythema nodosum, and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician.(AU)

Introducción: La enfermedad de Behçet (EB) es una vasculitis sistémica de causa desconocida. El espectro de la enfermedad abarca desde manifestaciones mucocutáneas hasta otras enfermedades de órganos con morbilidad relevante. Se han descrito asociaciones entre la gravedad de la enfermedad y el sexo masculino, la edad de inicio más temprana y la presencia de eritema nudoso. Objetivos: Evaluar los factores clínicos asociados con las manifestaciones de enfermedad grave en una cohorte de un solo centro. Métodos: Estudio de cohorte longitudinal, prospectivo y unicéntrico con pacientes seguidos en una clínica ambulatoria especializada entre 1981 y 2020. La EB grave se definió como una puntuación Krause total clinical severity score≥4 puntos. Resultados: Se incluyeron 243 pacientes, de los cuales el 31% eran varones, con un tiempo de seguimiento medio de 14,6 años. En cuanto a las manifestaciones orgánicas, todos los pacientes presentaron manifestaciones mucosas (n=243, 100%), 133 (55%) piel, 104 (43%) articular, 71 (29%) ocular, 48 (20%) afectación vascular, 47 (19%) neurológica, 22 (9%) gastrointestinal y 1 (0,4%) cardiaca por EB; 156 (64%) pacientes fueron clasificados como con EB grave. La EB severa fue más frecuente en hombres (OR=2,004, p=0,024), aumentando con la edad (OR=1,021 por año, p=0,037), en presencia de manifestaciones cutáneas (OR=4,711, p<0,001), específicamente eritema nodosum (OR=8,381, p<0,001) y pseudofoliculitis (OR=2,910, p<0,001). En el modelo multivariado, las variables asociadas de forma independiente con el EB grave fueron el sexo masculino (OR ajustado=1,961, p=0,047), eritema nudoso (OR ajustado=8,561, p<0,001) y pseudofoliculitis (OR ajustado=2,372, p=0,007). Discusión: El sexo masculino, el eritema nudoso y la pseudofoliculitis se asociaron de forma independiente con formas graves de DB y, por lo tanto, deberían servir como signos de advertencia para el médico.(AU)

Systemic vasculitis: one year in review 2022.

Systemic vasculitis are rare heterogeneous disorders potentially involving any organ and system with a relevant burden of mortality and comorbidity.As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis.

Different epidemiologic profiles of systemic vasculitis between Brazil and Peru-preliminary results in two referral centers from both countries.

Little is known about the epidemiology of systemic vasculitis in South American countries. The aim of this study is to compare the prevalence of systemic vasculitides in two vasculitis referral centers from Brazil and Peru. A cross-sectional study was performed and all patients above 18 years of age, with at least 6 months of follow-up and who met classification or diagnosis criteria for the most common forms of vasculitis, were included. A total of 562 patients with systemic vasculitis were analyzed, 345 (61.4%) from Brazil and 217 (38.6%) from Peru. The frequency of Behçet's disease (37.9% vs. 1.8%; p < 0.0001), Takayasu arteritis (TAK) (25.2% vs. 6.9%; p < 0.0001), and giant cell arteritis (9.8% vs. 0.9%; p < 0.0001) was higher in the Brazilian center than the Peruvian one. On the other hand, the frequency of microscopic polyangiitis (MPA) (67.3% vs. 2.8%; p < 0.0001) and renal-limited vasculitis (2.8% vs. 0.0%; p = 0.009) was higher in the Peruvian center. No differences were found concerning other forms of vasculitis. At diagnosis, Brazilian patients with TAK, granulomatosis with polyangiitis, and MPA were younger than Peruvian patients. Epidemiologic differences in the frequency of systemic vasculitis are observed between a vasculitis referral center from Brazil and another from Peru. Key Points • Significant differences are observed regarding the epidemiologic profile of systemic vasculitis between Brazil and Peru. • MPA is the predominant form of vasculitis in Peru while BD and TAK are the most frequent forms of vasculitis in Brazil. • The age at diagnosis of TAK, MPA, and GPA was lower in Brazilian patients than in Peruvian patients.

A case report of a severe neonatal systemic vasculitis on the first day of life.

BACKGROUND: Neonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren's syndrome, BehÒ«et's disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate. CASE PRESENTATION: In the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred. He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy. The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development. CONCLUSION: This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.

Investigating the forensic pathological characteristics of systemic vasculitis: A retrospective study of 20 deaths caused by systemic vasculitis.

Systemic vasculitis (SV) is a condition characterized by vascular inflammatory disease that often involves the medium and small arteries of various organs throughout the body. SV is difficult to diagnose due to the diversity of clinical symptoms and manifestations, and only tissue biopsy is of great significance. Even so, complications or secondary lesions of SV can also lead to death. In forensic medicine, we can often observe multiple vasculitis in histological observations, which is easily overlooked as a primary cause of death in the final diagnosis. Twenty SV cases were registered in our institution from a total of 1088 completed autopsies, which represents 1.83% of the total autopsies. The ages of these 20 SV patients ranged from 16 to 73 years, and the mean age was 41.1 ± 15.9 years. SV usually involves multiple organs, such as the heart, lung, liver, kidney, gastrointestinal system and brain, simultaneously. The intensity of the lesions in the heart and kidney seemed to be more severe than the lesion intensity in other organs in most cases. The causes of death were identified as acute myocarditis (8 cases), acute heart failure (3 cases), cerebral artery rupture (3 cases), cardiovascular artery rupture (2 cases), acute interstitial pneumonia (2 cases), aortic aneurysm rupture (1 case) and acute renal failure (1 case). The typical histopathological changes (smooth muscle degeneration, fibrinoid necrosis, inflammatory cell infiltration and microthrombosis) of arteries observed in this study were of great significance for diagnosing SV. In this article, we try to analyse and summarize the lesion characteristics in cases of death caused by SV in order to provide some help for forensic workers in identifying such cases.