Rheumatoid vasculitis in 2023: Changes and challenges since the biologics era.

BACKGROUND: Significant changes in the epidemiology and natural history of rheumatoid vasculitis (RV) have occurred with the introduction of biological therapies such as TNF inhibitors (TNFi) and rituximab. PURPOSE: This scoping review aims to address the key current challenges and propose updated criteria for RV. This will aid future descriptive observational studies and prospective therapeutic trials. METHODOLOGY: The MEDLINE database was searched for eligible articles from inception through December 2022. Articles were selected based on language and publication date after 1998, corresponding to the approval of the first TNFi in rheumatic diseases. RESULTS: Sixty articles were included in the review. The mean incidence of RV has decreased since the approval of biologic therapies in RA, from 9.1 (95% CI: 6.8-12.0) per million between 1988 and 2000 to 3.9 (95% CI: 2.3-6.2) between 2001 and 2010, probably due to significant improvement in RA severity and a decrease in smoking habits. Factors associated with an increased risk of RV include smoking at RA diagnosis, longer disease duration, severe RA, immunopositivity, and male gender (regardless of age). Homozygosity for the HLA-DRB104 shared epitope is linked to RV, while the presence of HLA-C3 is a significant predictor of vasculitis in patients without HLA-DRB104. Cutaneous (65-88%), neurologic (35-63%), and cardiac (33%) manifestations are common in RV, often associated with constitutional symptoms (70%). Histologic findings range from small vessel vasculitis to medium-sized necrotizing arteritis, but definite evidence of vasculitis is not required in the 1984 Scott and Bacon diagnostic criteria. Existing data on RV treatment are retrospective, and no formal published guidelines are currently available. CONCLUSION: The understanding of RV pathogenesis has improved since its initial diagnostic criteria, with a wider range of clinical manifestations identified. However, a validated and updated criteria that incorporates these advances is currently lacking, impeding the development of descriptive observational studies and prospective therapeutic trials. PRIMARY FUNDING SOURCE: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Successful peficitinib monotherapy for the new-onset skin manifestations of rheumatoid vasculitis after long-term treatment with tocilizumab for rheumatoid arthritis.

Rheumatoid vasculitis (RV) is a severe extra-articular systemic manifestation of rheumatoid arthritis (RA). Its prevalence has been decreasing for decades because of improved early diagnosis of RA and advances in RA treatment, but it remains a life-threatening disease. The standard treatment for RV has been a glucocorticoid and disease-modifying antirheumatic drugs. Biological agents, including antitumour necrosis factor inhibitors, are also recommended for refractory cases. However, there are no reports of Janus kinase (JAK) inhibitor use in RV. We experienced a case of an 85-year-old woman with a 57-year history of RA who had been treated with tocilizumab for 9 years after receiving three different biological agents over 2 years. Her RA seemed to be in remission in her joints, and her serum C-reactive protein had decreased to 0.0 mg/dL, but she developed multiple cutaneous leg ulcers associated with RV. Because of her advanced age, we changed her RA treatment from tocilizumab to the JAK inhibitor peficitinib in monotherapy, after which the ulcers improved within 6 months. This is the first report to indicate that peficitinib is a potential treatment option for RV that can be used in monotherapy without glucocorticoids or other immunosuppressants.

Acute Meningoencephalitis after COVID-19 Vaccination in an Adult Patient with Rheumatoid Vasculitis.

We herein report a 72-year-old woman with rheumatoid vasculitis who exhibited a depressed level of consciousness after receiving the first dose of the Pfizer-BioNTech mRNA BNT162b COVID-19 vaccine and was diagnosed with meningoencephalitis. Although there was no confirmatory examination, the diagnosis was based on magnetic resonance imaging (MRI) findings and etiological assessments, including microbiological and autoimmune investigations. Both intravenous steroid pulse and gammaglobulin therapies alleviated the patient's symptoms, and the MRI findings improved. Although the efficacy of COVID-19 vaccination has been widely accepted, such neurologic complications might occur in patients with rheumatoid diseases or vasculitis syndromes.

Rheumatoid vasculitis: study of 41 cases. / Vasculitis reumatoide: estudio de 41 casos.

AIM: To describe the clinical manifestations, evolution and treatment of patients with rheumatoid vasculitis. METHODS: Retrospective study (1975-2017) of all patients diagnosed with rheumatoid vasculitis in 2 Rheumatology Services. RESULTS: A total of 41 patients were included, 17 (41.5%) males and 24 (58.5%) females; mean age at diagnosis: 67 ± 9 years; duration of rheumatoid arthritis: 10 ± 8.3 years. Most patients had erosive disease, 33 (80%). Rheumatoid factor and anticitrullinated antibodies were positive in all patients. Constitutional symptoms were present in 30 (73%) patients and extra-articular manifestations in 17 (41%) patients. The clinical manifestations of rheumatoid vasculitis were mainly: cutaneous 28 (68%), and polyneuritis 26 (63%). All patients were treated with glucocorticoids. An immunosuppressant was associated in 24 (58.5%) patients. Five (12%) patients were treated with the association of glucocorticoids and a biologic treatment. The mortality after 2years of follow-up was 33%, the most common causes being infection and progression of the vasculitis. The frequency of rheumatoid vasculitis has decreased over the last decade. CONCLUSION: The clinical manifestations of rheumatoid vasculitis were similar to previous studies. The frequency of rheumatoid vasculitis seems to decrease. However, the clinical picture and severity remains invariable.

18 F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with polymyalgia rheumatica: Screening for vasculitis. / 18 F-FDG PET/TC en pacientes con polimialgia reumática: despistando vasculitis.

OBJECTIVE: Polymyalgia rheumatica (PR) can be associated with large vessel vasculitis (LVV). We evaluate the diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and its impact on the treatment of LVV associated with PR. MATERIALS AND METHODS: Retrospective study of patients diagnosed with PR. Data was collected from health records. Blood analysis included acute-phase reactants (APR), C-reactive protein (CRP) and erythrocyte sedimentation rate. An 18F-FDG PET/CT scan was performed in those patients whose symptoms persisted, in those with elevated APR, those who required higher doses of steroids or those who had atypical features of PR (low-grade fever, weight loss, among others). RESULTS: Twenty-three were eligible; 48% (n = 11) of the patients were diagnosed with LVV associated with PR. The site was heterogeneous, but mostly involved the aorta. In 80% of the patients with LVV, a disease-modifying antirheumatic drug was added to their treatment. Elevated CRP values were associated with the likelihood of presenting LVV. CONCLUSIONS: LVV is not uncommon, clinical features and elevated CRP levels should raise suspicion of LVV associated with PR. 18F-FDG PET/CT is useful in identifying LVV associated with PR.

Severe Mononeuritis Multiplex due to Rheumatoid Vasculitis in Rheumatoid Arthritis in Sustained Clinical Remission for Decades.

Rheumatoid vasculitis (RV) usually occurs in patients with refractory rheumatoid arthritis (RA). An 80-year-old woman was transferred to our hospital because of muscle weakness and paresthesia in all 4 limbs. She had been diagnosed with RA 30 years ago and achieved sustained clinical remission. At presentation, polyarthritis and drop foot were observed, and rheumatoid factor was prominently elevated. A peripheral nerve conduction test revealed mononeuritis multiplex in her limbs. We suspected that RV had developed rapidly despite RA having been stable for many years and started immunosuppression therapy with steroids combined with azathioprine. The treatment prevented worsening of muscle weakness and paresthesia.

Vasculitic Neuropathies.

Vasculitic neuropathies are disorders that result from inflammation in the peripheral nerves' vascular supply, resulting in ischemic injury. These disorders may be a result of systemic inflammation or may be confined to the peripheral nervous system. Causative etiologies include primary systemic vasculitis, vasculitis secondary to other conditions such as primary connective tissue disorders, infectious, paraneoplastic, and drug-induced conditions, and nonsystemic vasculitic neuropathy. Early recognition and treatment of these conditions is imperative to prevent substantial morbidity and mortality. The goal of this review is to provide an organization of the vasculitic neuropathies and an overview of principles of diagnosis and treatment for the clinical neurologist.

Inflammatory arthritis and crystal arthropathy: Current concepts of skin and systemic manifestations.

Systemic inflammatory disorders frequently involve the skin, and when cutaneous disease develops, such dermatologic manifestations may represent the initial sign of disease and may also provide valuable prognostic information about the underlying disorder. Familiarity with the various skin manifestations of systemic disease is therefore paramount and increases the likelihood of accurate diagnosis, which may facilitate the implementation of an appropriate treatment strategy. An improvement in quality of life and a reduction in the degree of morbidity may also be a realized benefit of accurate recognition of these skin signs. With this context in mind, this review highlights the salient clinical features and unique dermatologic manifestations of rheumatoid arthritis, adult-onset Still's disease, and the crystal arthropathy, gout.

Cutaneous vasculitis in rheumatologic disease: Current concepts of skin and systemic manifestations.

Cutaneous vasculitis may be limited to the skin, a manifestation of systemic vasculitis, or a sign of an important underlying disease state. A thorough and systematic approach is required for accurate diagnosis and evaluation of such patients to enable appropriate management of the vasculitis and any associated condition. Occasionally, cutaneous vasculitis is a manifestation or presenting sign of connective tissue disease, such as systemic lupus erythematosus, Sjögren syndrome, or another condition. Such patients are at risk for poor outcomes related to systemic manifestations of vasculitis, as well as increased severity of the underlying disease. Recognition of this important subset of patients with skin vasculitis enables appropriate workup and successful management.

Rheumatoid Vasculitis: A Diminishing Yet Devastating Menace.

PURPOSE OF REVIEW: Rheumatoid vasculitis (RV) is an unusual complication of long-standing rheumatoid arthritis, which is characterized by the development of necrotizing or leukocytoclastic vasculitis involving small or medium-sized vessels. In this review, we aim to provide an update on the epidemiology, pathogenesis, clinical presentation, and management of this challenging extra-articular manifestation. RECENT FINDINGS: RV is heterogenous in its clinical presentation depending on the organ and size of blood vessels involved. The most common organs involved are the skin and peripheral nerve. Based on recent population studies, the incidence has significantly decreased with early recognition and the advent of immunosuppressive drugs and biologics; however, the mortality rates remain high. RV remains a serious extra-articular manifestation of RA that needs to be promptly recognized and treated. No consensus is available on treatment, given the ongoing debate of whether the biologics can trigger or treat RV.

Rheumatoid vasculitis: early presentation of rheumatoid arthritis.

Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis and may affect small-to-medium-sized vessels. Here, we report a case of a 49-year-old man who presented with amaurosis fugax in the left eye, symmetric polyarthritis, Raynaud's symptoms and paraesthesia in both lower extremities. The patient subsequently experienced right foot drop, nail fold infracts and gangrene of his right second toe. He was found to have a high titre of rheumatoid factor and treatment with rituximab and high dose of corticosteroids led to significant improvement of his symptoms. This is rare case describing the early onset of rheumatoid vasculitis in a patient with rheumatoid arthritis.

Connective Tissue Disorder-Associated Vasculitis.

Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years.

New insight into the rheumatoid vasculitis.

Vasculitis in rheumatoid arthritis (rheumatoid vasculitis, RV) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic inflammation. Rheumatoid vasculitis is an unusual complication of longstanding, severe rheumatoid arthritis (RA). While RA affects the body's joints, vasculitis is a condition in which blood vessels become inflamed. Rheumatoid vasculitis occurs in approximately 2 to 5% of patients who have RA. The blood vessels most often involved are arteries that bring blood to the skin, nerves, and internal organs. Veins can also be involved. Rheumatoid vasculitis is skin condition that is a typical feature of RA, presenting as peripheral vascular lesions that are localized (purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities). The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an autoimmune process is suggested. Compared to other forms of vasculitis, there has been relativejy little research in recent years on the specific entity of RV. There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of a better treatment of the underlying RA. In the present review, we discuss the clinical features, laboratory tests, the pathogenesis of RV.

[Complications and systemic manifestations of rheumatoid arthritis]. / Complications et atteintes systémiques de la polyarthrite rhumatoïde.

Rheumatoid arthritis (RA), in addition to the traditional joint damage can affect all organs as a systemic disease. Extra-articular manifestations of RA are highly variable ranging from rheumatoid nodules (most common) to rheumatoid vasculitis presenting a significant morbidity and mortality (49% at 5 years). With the new algorithms of treatment (earlier) and the use of biologics, the incidence of severe extra-articular manifestations decreases. Regarding the treatment of rheumatoid vasculitis, rituximab looks promising. RA also increases cardiovascular risk and the risk of osteoporosis. It is therefore important to identify these risks and, if appropriate, treat them. Collaboration with the general practitioner is essential in this situation.

Vasculitis associated with rheumatoid arthritis: a case-control study.

OBJECTIVE: The aim of this study was to determine the clinical correlates and predictors of rheumatoid vasculitis (RV). METHODS: A retrospective cohort of patients with RV evaluated at a tertiary referral centre between 1 January 2000 and 1 January 2010 was identified. RV cases were compared in a 1:2 ratio to controls (RA without vasculitis) to identify risk factors for developing RV. RESULTS: Eighty-six RV cases (58% women, 88% white) were identified. Histopathological confirmation was available for 58% of patients. Cutaneous vasculitis was the most common presentation, followed by vasculitic neuropathy. The median age at presentation was 63 years and the median duration of RA was 10.8 years. One third were current smokers. The majority were seropositive and had elevated inflammatory markers. Treatment was with a range of immunomodulating agents. At 6 months, 38% of patients achieved complete remission, 52% had partial improvement and 10% noted no clinical improvement. Thirty-six per cent relapsed by 5 years and 26% died. After adjusting for age and disease duration, current smoking at RA diagnosis [odds ratio (OR) 1.98], coexistent peripheral vascular disease (OR 3.98), cerebrovascular disease (OR 6.48), severe RA (OR 2.02) (characterized by radiographic erosions, nodulosis on clinical examination or requirement of joint surgery) and the use of biologics (OR 2.80) were found to increase the odds for developing RV; the use of HCQ (OR 0.54, CI 0.31, 0.94) and low-dose aspirin (OR 0.42, CI 0.21, 0.85) was associated with decreased odds for developing RV. CONCLUSION: This largest single-centre series of patients with RV suggests that even in recent years, RV remains a serious complication of RA and is associated with significant mortality.

Will antirheumatic treatment improve cardiovascular outcomes in patients with rheumatoid arthritis?

In recent years, the scientific community has gained significant insight into the complex interaction between inflammation and the cardiovascular system in patients with rheumatoid arthritis (RA), which leads to increased cardiovascular (CV) morbidity and mortality in these patients. Our common understanding of this association is that persistent inflammation contributes to the development of premature atherosclerosis. Consequently, the question arises whether control of inflammation with antirheumatic treatment will be able to improve CV outcome. While there are a lot of data that demonstrate improvement of numerous CV surrogate markers in patients treated with virtually all antirheumatic drug classes, there is much less information about the possible translation of these beneficial effects into improved CV outcome. In summary, the published evidence suggests that tumor necrosis factor (TNF) alpha inhibitors may improve CV outcome. The same is true for methotrexate (MTX). However, it is not clear whether MTX works via suppression of inflammation or through drug specific mechanisms. For other traditional disease-modifying antirheumatic drugs and biologic therapies, there are no convincing data for improved CV outcome. Only a few drugs (glucocorticoids and NSAIDs) have been associated with increased CV risk. Treating RA aggressively, as recommended by current guidelines, is likely to have a beneficial effect on CV outcomes.

Vasculitis of the gallbladder in early rheumatoid arthritis.

Vasculitis secondary to rheumatoid arthritis (RA) usually occurs in patients with high circulating titres of rheumatoid factor and established, chronic disease. Vasculitis of the gallbladder causing acute cholecystitis is an extremely rare manifestation of rheumatoid vasculitis. To our knowledge, this is the first case in which vasculitis occurred early in the course of disease. We report the case of a localised gallbladder vasculitis in a 74-year-old, newly diagnosed male patient with RA. He presented with acute abdominal pain, a history of constitutional symptoms and a 1-week history of polyarthritis of his wrist and hands. Cholecystitis was diagnosed clinically and radiologically and he underwent a laparoscopic cholecystectomy. Histopathology of the gallbladder confirmed cholecystitis and gallstones but in addition found small vessel vasculitis and rheumatoid nodules. This case illustrates that rheumatoid vasculitis can occur early in the onset of RA. Additionally, although rare, the gallbladder can be a site of localised rheumatoid vasculitis.

Foot ulcers caused by rheumatoid vasculitis in a patient with rheumatoid arthritis undergoing etanercept treatment.

A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented with chronic ulcers on both feet while undergoing treatment with etanercept. Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor (TNF) agents are known to induce vasculitis, vasculitis can also be caused by active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF therapy must be evaluated carefully.