Central Nervous System Vasculitis: Primary Angiitis of the Central Nervous System and Central Nervous System Manifestations of Systemic Vasculitis.

Central nervous system vasculitis (CNSV) is a group of disorders leading to inflammatory vasculopathy within the brain, spinal cord, and leptomeninges. CNSV is divided into primary angiitis of the central nervous system (PACNS) and secondary CNSV based on the underlying etiology. PACNS is a rare inflammatory disorder with poorly understood pathophysiology and heterogeneous and highly variable clinical features. The diagnosis depends on a combination of clinical and laboratory variables, multimodal imaging, and histopathological examination as well as exclusion of mimics. Several systemic vasculitides, infectious etiologies and connective tissue disorders have been shown to cause secondary CNSV and require prompt recognition.

Multicentre case-control study evaluating the safety of anti-SARS-CoV-2 vaccines in a cohort of patients with systemic vasculitis.

OBJECTIVES: Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV. METHODS: Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination. RESULTS: 107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well. CONCLUSIONS: These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.

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.

Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study.

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn's disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

Rare case of bilateral wrist and foot drop from SLE-related vasculitic polyneuropathy.

Systemic lupus erythematosus (SLE) is a heterogeneous, chronic, inflammatory, autoimmune disease characterised by multiorgan involvement and the production of multiple autoantibodies. Neurological manifestations in SLE patients are frequently reported-the prevalence is 37%-90%. We present a unique case where the patient presented with bilateral wrist and foot drop for 4 days, which later led to the diagnosis of SLE-related vasculitic polyneuropathy. During the course of treatment, the patient received prednisone, rituximab and hydroxychloroquine. At 6-month follow-up, patient had reported significant improvement in her weakness with increased mobility in upper and lower extremities. Prompt diagnosis and treatment are necessary in these cases to prevent disease progression and morbidity.

Factors Affecting the Health of Retinal Vessels in Human Immunodeficiency Virus Patients Beginning Anti-Retroviral Therapy.

HIV patients responding to antiretroviral therapy (ART) have a high burden of cytomegalovirus (CMV) and display accelerated cardiovascular change assessed systemically. We assessed the effects of HIV, ART and CMV on retinal artery calibers (RAC), as a non-invasive measure of vasculopathy in HIV patients beginning ART. We analysed 79 HIV patients beginning ART in Jakarta, Indonesia, with a median (range) age of 31 (19-48) years. RAC was assessed using Image J software from fundus photos of both eyes, before ART (V0) and after 3-12 months (V3-V12). CMV DNA and antibodies were assessed. Systemic vascular pathology was assessed by carotid intima media thickness (cIMT). Multivariable models assessed which variables best predicted RAC values at V12. HIV patients had narrower retinal arteries and higher levels of CMV antibodies than healthy controls. RAC decreased over 12 months of ART (p < .0001). Right RAC correlated with CMV IE-1 antibody, while the left RAC at V3 correlated with cIMT. Multivariable models linked RAC at V12 with detectable HIV RNA at V12 and declared use of alcoholic drinks, while a smoking habit was protective. Decreases in RAC in HIV patients responding to ART suggest progressive microvascular change distinct from changes assessed in large vessels. Correlations with CMV IE-1 antibodies suggest the decline in RAC may be accelerated by frequent reactivations of CMV. This may be a feature of severe HIV disease before ART, confirmed by associations with high baseline HIV RNA in multivariable models. Links with alcohol consumption and smoking testify to a complex pattern of modifiable risk factors.

Asymptomatic rheumatoid meningitis revealed by magnetic resonance imaging, followed by systemic rheumatic vasculitis: A case report and a review of the literature.

We report the case of a 66-year-old man with seropositive rheumatoid arthritis who developed neurologically asymptomatic rheumatoid meningitis (RM) revealed by MRI. RM worsened and chest CT showed pericardial effusion, pleural effusion, and bilateral consolidation, and his serum C3 level was decreased. We diagnosed systemic rheumatic vasculitis based on these findings. After a review of more than 20 previously reported cases of RM, this is the first case of RM without central nerve system symptoms.

Current State of Precision Medicine in Primary Systemic Vasculitides.

Precision medicine (PM) is an emerging data-driven health care approach that integrates phenotypic, genomic, epigenetic, and environmental factors unique to an individual. The goal of PM is to facilitate diagnosis, predict effective therapy, and avoid adverse reactions specific for each patient. The forefront of PM is in oncology; nonetheless, it is developing in other fields of medicine, including rheumatology. Recent studies on elucidating the genetic architecture of polygenic and monogenic rheumatological diseases have made PM possible by enabling physicians to customize medical treatment through the incorporation of clinical features and genetic data. For complex inflammatory disorders, the prevailing paradigm is that disease susceptibility is due to additive effects of common reduced-penetrance gene variants and environmental factors. Efforts have been made to calculate cumulative genetic risk score (GRS) and to relate specific susceptibility alleles for use of target therapies. The discovery of rare patients with single-gene high-penetrance mutations informed our understanding of pathways driving systemic inflammation. Here, we review the advances in practicing PM in patients with primary systemic vasculitides (PSVs). We summarize recent genetic studies and discuss current knowledge on the contribution of epigenetic factors and extracellular vesicles (EVs) in disease progression and treatment response. Implementation of PM in PSVs is a developing field that will require analysis of a large cohort of patients to validate data from genomics, transcriptomics, metabolomics, proteomics, and epigenomics studies for accurate disease profiling. This multi-omics approach to study disease pathogeneses should ultimately provide a powerful tool for stratification of patients to receive tailored optimal therapies and for monitoring their disease activity.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Update on the epidemiology, risk factors, and outcomes of systemic vasculitides.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and giant cell arteritis (GCA) are the most common primary systemic vasculitides of the adult population, while polymyalgia rheumatica (PMR) is a clinical syndrome often associated with GCA. Incidence and prevalence rates of AAV have been increasing in the last decades, whereas those of GCA and PMR have remained stable. The mutual interplay between environmental and genetic risk factors leading to the development of these diseases has been further analyzed in the last years. The role of infectious agents has repeatedly been studied with regard to Staphylococcus aureus, associated with relapse in granulomatosis with polyangiitis, and Herpes zoster, potentially contributing to GCA development. Remission of disease and prevention of disease-related complications are the most important outcomes for all systemic vasculitides. Although these goals are achieved in the majority of patients receiving modern therapies, the prevention of treatment-related complications, especially glucocorticoid side effects, is still an unmet need that is common to AAV, GCA, and PMR.

One year in review 2018: systemic vasculitis.

Systemic vasculitis are heterogeneous, complex and disabling disorders. Following the previous annual reviews of this series, this paper gives a brief overview on current knowledge about recent literature on small- and large-vessel systemic vasculitis, with a specific focus on pathogenetic and clinical aspects, novel possible disease-related biomarkers and current and future therapies that are in the pipeline.

Acute gastric dilatation in a patient with lupus nephritis: An uncommon presentation of lupus mesenteric vasculitis.

Abdominal symptoms are common in patients with lupus nephritis and are often attributed to drugs or uremia per se. Lupus mesenteric vasculitis (LMV) or lupus enteritis is a rare entity reported in patients with active systemic lupus erythematosus. It usually occurs in patients with a long-standing history of lupus with high disease activity. Usually, small bowel is predominantly affected. The stomach and rectum are spared in view of significant collateral circulation. Here, we describe an 18-year-old boy who presented with nephrotic syndrome without any extrarenal features of lupus. On subsequent evaluation, he was found to have active lupus nephritis. He developed acute gastric dilatation secondary to extensive LMV. Imaging showed an extensive involvement of gastrointestinal tract from the stomach to the sigmoid colon, sparing the rectum. To the best of our knowledge, this is the first report of LMV presenting as acute gastric dilatation.

Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and L-arginine metabolism in mice.

Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO2- were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO2- levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO2- levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

Efficacy of Cryofiltration for Treatment of Mixed Cryoglobulinemia: A Report of Four Cases.

Cryoglobulinemia can induce systemic vasculitis affecting various organs such as skin, peripheral nerves, and kidney. The disease can induce chronic organ failure and even be life-threatening. Cryofiltration has been applied for the treatment of cryoglobulinemic vasculitis. We have experienced four cases with mixed cryoglobulinemia showing severe and progressive clinical manifestations, including skin purpura, nephrotic syndrome, acute kidney injury, and peripheral neuropathy. Cryofiltration in conjunction with conventional pharmacological therapies appeared to be safe and effective. After the treatments, plasma cryoglobulins were markedly reduced and the disease was well controlled. Although its efficacy has not yet been well established, this report can be another evidence showing efficacy of cryofiltration for treatment of mixed cryoglobulinemia.

[Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment]. / Krioglobulinemicheskii vaskulit, assotsiirovannyi s virusom gepatita S: 20-letnii opyt lecheniia.

AIM: To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). SUBJECTS AND METHODS: Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients' survival was studied; multivariate logistic regression analysis was carried out. RESULTS: 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). CONCLUSION: HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

Update on systemic vasculitides.

Management of systemic vasculitis has been revolutionised over the last decade with the introduction of targeted biological agents. With an increase in both the prevalence and the recognition of vasculitis as well as the high cost of these agents, it is important to ensure their most optimal utilisation. The goals of vasculitis therapy include the induction and maintenance of remissions, preventing relapses, reducing the toxicity of therapy with the aim of reducing morbidity and mortality as well as improving the quality of life of those afflicted. This review focuses on the recent advances in the diagnosis, surveillance and treatment of these conditions.