Treatment Of Systemic Vasculitis Research Articles

Signal Regulatory Protein α Expression in Systemic Vasculitis.

Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis. Immunohistochemical staining for SIRPα was performed on temporal artery (TA), kidney, and lung biopsy samples from patients with giant cell arteritis (GCA), patients with microscopic polyangiitis (MPA), patients with granulomatosis with polyangiitis (GPA), and patients without vasculitis. A score of SIRPα+ expression was calculated, derived from the percentages of monocytes, macrophages, and dendritic cells and neutrophils with different staining intensities in affected tissues. A total of 46 samples from patients with different vasculitides (GCA, MPA, and GPA) were included in the study. Tissue samples included TA samples from 15 patients with GCA; kidney samples from 11 and 9 patients with GPA and MPA, respectively; and lung samples from 11 patients with GPA. Most tissue samples from patients with active vasculitis (15 of 15 TA samples, 17 of 20 kidney samples, and 9 of 11 lung samples) showed SIRPα staining. SIRPα staining intensity was less in kidney samples compared to TA and lung samples. This study demonstrates high-level expression of SIRPα in macrophages and monocytes in affected tissue in systemic vasculitis. These findings provide a foundation for further studies exploring the role of the SIRPα-CD47 pathway in the pathogenesis of systemic vasculitis and the potential for the blockade of SIRPα and/or the depletion of SIRPα+ cells as treatment of systemic vasculitis.

Symposium 10: Spotting EGPA from Asthma Populations and How Co-Care Works Between Rheumatology and Respiratory Physicians: A Case Sharing

Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis characterized by asthma, eosinophilia, and vasculitic organ involvement. This rare disease poses diagnostic challenges within the domain of severe asthma. Recognizing EGPA within the asthmatic cohort is therefore crucial for appropriate management and improved patient outcomes. Moreover, effective collaboration between rheumatologists and respiratory physicians is vital for the comprehensive care of EGPA patients. This scientific lecture aims to discuss the identification of EGPA in individuals with asthma and highlight the importance of co-care between rheumatology and respiratory medicine. This lecture will begin by providing an overview of EGPA, its clinical manifestations, and the challenges associated with differentiating it from severe asthma. The crucial identification of distinctive clinical features, such as refractory asthma, peripheral eosinophilia, and systemic symptoms, which serve as beacons for the presence of EGPA, will be discussed. Diagnostic tools encompassing imaging, laboratory tests, and biopsy techniques are explored, focusing on their utility in distinguishing EGPA from asthma. Concomitantly, the lecture will then shift its focus to the collaborative efforts required from rheumatologists and respiratory physicians in managing EGPA patients. The complementary roles of both specialties in achieving optimal patient outcomes will be discussed. Rheumatologists play a crucial role in the diagnosis and treatment of systemic vasculitis, including EGPA, while respiratory physicians provide expertise in managing asthma and respiratory complications. The case will highlight the importance of open communication, shared decision-making, and coordinated treatment plans to ensure comprehensive care for EGPA patients, addressing both their rheumatologic and respiratory needs. Real-life case will be shared to illustrate successful co-management models between rheumatology and respiratory medicine. These examples will underscore the benefits of a multidisciplinary approach, including improved disease management, reduced treatment-related complications, and enhanced patient satisfaction. In conclusion, identifying EGPA within the asthma population is crucial for appropriate management, and effective collaboration between rheumatology and respiratory physicians is essential for comprehensive care. This scientific lecture aims to provide insights into spotting EGPA among asthma patients and emphasize the significance of co-care between these specialties, ultimately improving patient outcomes and quality of life.

Regulatory T cells and systemic vasculitis.

Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent advances in the role of Treg and interleukin (IL)-10 in the pathogenesis and treatment of systemic vasculitis, including giant cell arteritis (GCA), Takayasu arteritis, Behçet's disease, antineutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV), and cryoglobulinemia associated vasculitis. Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Decreased peripheral blood frequencies of Treg are described in all vasculitis when compared to healthy donors. Altered Treg functions are reported in GCA, Takayasu arteritis, AAV, and Behçet's disease with different mechanisms proposed. Treatment with biologics, and sometimes other immunosuppressants, may restore Treg frequencies and/or immune activity with significant differences in active disease or disease in remission in several systemic vasculitis. IL-10 is elevated in GCA, AAV, cryoglobulinemia associated vasculitis. In Behçet's disease, IL-10 is decreased in peripheral blood and elevated in saliva. In Takayasu arteritis, IL-10 levels were essentially elevated in patients' vessel wall. Several new therapeutic approaches targeting Treg and Il-10 (low dose IL-2, CAR Treg…) are developed to treat patients with systemic vasculitis. Treg and IL-10 play a central role in the regulation of inflammation in vasculitis and new targeting approaches are emerging.

AB0627 Evaluation of internal consistency, feasibility, and reliability of the Italian version of ANCA-associated vasculitis patient-reported outcome (AAV-PRO_ita) questionnaire: preliminary results from a multicenter study on a large cohort of Italian patients

BackgroundThe ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire is a 29-item disease-specific PRO measure for AAV[1]. The Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) was translated in collaboration with Oxford and Bristol University (UK) and was preliminarily tested on a single-center Italian cohort[2].ObjectivesThe main objective of this multicentric study was to assess the internal consistency, feasibility, and reliability of the AAV-PRO_ita in a large cohort of Italian AAV patients. The secondary objective was to investigate the clinical characteristics of AAV patients associated with AAV-PRO_ita domains.MethodsThe AAV-PRO_ita is describes the following disease domains: (1) organ-specific and systemic symptoms and signs (SSS); (2) physical function (PF); (3) social and emotional impact (SEI). In this study, Italian-speaking AAV patients were recruited from Italian Centres (N=13) with a large experience in the diagnosis and treatment of systemic vasculitis, belonging to the Vasculitis Study Group of the Italian Society of Rheumatology. Inclusion criteria were: a confirmed diagnosis of GPA, MPA, or EGPA; ANCA positivity in at least once occasion or biopsy-proven AAV; and age ≥18 years old. Participants completed the AAV-PRO_ita at three different time-points: baseline, after 5-7 days, and at month 3.Results229 AAV-patients (56.3% women) with a median age of 61 (IQR 51-72) were recruited and completed the questionnaires. The subtype of AAV was mainly GPA (131, 57.2%), followed by EGPA (58, 25.3%), and MPA (40, 17.5%). Median BVASv3 at baseline was 0 (IQR 0-3), whereas the median BVASv3 at the onset of disease was 14 (IQR 9-20). Participants had a median duration of disease of 67 (IQR 24-126) months. Patients who experienced at least one relapse, one hospitalization, and one severe infection were 40.2%, 53.3%, and 24%, respectively. 83% of the patients were on immunosuppressant therapy and 71.6% were still receiving glucocorticoids (GC).AAV-PRO_ita questionnaire had good internal consistency (Cronbach’s Alpha range 0.81-0.93) and good test-retest reliability (ICCs range 0.93-0.96). Item response rates were high overall (maximum 0.87% missing data), supporting the feasibility of the questionnaire.Concerning the domains of the questionnaire, female AAV patients scored higher (i.e. worse) in all three domains, especially in the SEI domain (p-value<0.001). Older participants (≥65 years) scored higher in the PF domain (p-value<0.05) in all three times of self-completions of the questionnaire. The ongoing treatment also influenced the results. In fact, patients on GC showed higher scores in the PF domain (p-value=0.003) and SEI domain (p-value=0.021). The VDI value seemed to be related to AAV-PRO_ita scores more than disease duration or disease activity, especially in the SSS domain (ρ>0.3, p-value<0.001). Conversely, subtype of AAV did not influence the item scores.ConclusionThe AAV-PRO_ita questionnaire is a new 29-item, disease-specific PRO measure for use in AAV in the Italian language. It is a self-administered Italian questionnaire with good internal consistency, feasibility, and reliability. AAV-PRO_ita proved to be a useful tool to explore the AAV patient’s perception of quality of life, and it could become an important way of measuring the unmet needs of AAV patients.

Diagnostic and Therapeutic Challenges of Vasculitis.

Systemic vasculitis can be a challenge to differentiate from other forms of vasculopathy. Because treatment for systemic vasculitis is disparate from that for other forms of vasculopathy, clinicians should strive for high diagnostic certainty. This review article aims to highlight the clinical, radiographic, and histologic clues to distinguish systemic vasculitis from mimics. Vasculitis should be considered in patients with preexisting conditions including autoimmune connective tissue diseases, multisystem manifestations, unexplained ischemic events, unusual radiographic findings, or signs of systemic inflammation. A multidisciplinary approach can be used among rheumatologists, vascular cardiologists, radiologists, and vascular interventionalists to raise diagnostic certainty in cases with large- and/or medium-vessel involvement. Recognition of cardiac manifestations, including myocarditis seen in forms of small-vessel vasculitis (eg, eosinophilic granulomatosis with polyangiitis) or coronary arteritis seen in forms of medium-vessel vasculitis (eg, polyarteritis nodosa and Kawasaki disease) is important owing to the associated mortality. Clinical phenotype, radiographic features, laboratory tests, and histology can help to differentiate vasculitis from noninflammatory vasculopathies and define the etiology of the vasculitis to help guide appropriate treatment. Various modalities of imaging can give clues to aid in diagnosis of vasculitis and can be considered in the context of physician preference and patient comorbidity. While conventional angiography can give important details regarding luminal anatomy and pressure gradients in medium- and large-vessel vasculitis, noninvasive imaging modalities such as computed tomographic angiography, magnetic resonance angiography, color Doppler ultrasound, and positron emission tomography/computed tomography are commonly used for both diagnosis and follow-up. Treatment for systemic vasculitis should be coordinated with an experienced rheumatologist.

Updates in cutaneous manifestations of systemic vasculitis.

The main purpose of this review is to present newly reported cutaneous manifestations of systemic vasculitis, updates in investigations to verify systemic involvement in cases with cutaneous vasculitis and new therapeutic guidelines. The spectrum of COVID-19-related vasculitis is also covered. Only a few reports highlighted new cutaneous presentations or associations with some systemic vasculitic entities. For example, the association of inflammatory disorders with Takayasu arteritis, the importance of considering Kawasaki disease in febrile children with erythema nodosum, the development of necrotic ulcers on fingers and toes in Behçet's disease and the possible presence of polyarteritis nodosa-like pathological features in vulvar ulcers of Behçet's disease. New attempts to classify cutaneous manifestations of giant cell arteritis (GCA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the diagnostic investigations for cutaneous vasculitis cases to verify systemic involvement are discussed. Treatment of systemic vasculitis with cutaneous vasculitis should be tailored according to disease status. A plethora of reports in the past 2 years focused on the broad spectrum of COVID-19 vasculitic manifestations. Although newly reported cutaneous manifestations of systemic vasculitis are relatively uncommon, the plethora of reports in the past 2 years on COVID-19 vasculitis necessitates the expansion of the classification of vasculitis associated with probable cause to include severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) vasculitis.

Actual possibilities and perspectives of biological drugs in treatment of systemic vasculitides. III. Biological drugs in giant cell arteritis

A review of the literary data about the hitherto exiting investigations on biological drugs (BDs) as an alternative of the corticosteroids (CSs) – the current basal therapy of giant cell arteritis (GCA) is presented. The TNF-alpha-inhibitors are already definitely discarded on the account of their inefficiency and inadequate tolerability. The favorable initial results of BDs against IL-1, CTLA4-iGg1 and especially IL-12/23 should receive a reliable assessment after completion of the additional large-scale investigations. Indisputably only the data on efficacy of tocilizumab (anti-IL-6) for induction and maintenance of GCA remission and its marked CS-saving effect are convincing. Reasonably, TCM received a permission for use as adjunctive therapy in the management of GCA.

Difficulties in the differential diagnosis of granulomatosis with polyangiitis and scarring pemphigoid

The article presents a clinical case of a rare pathology. The patient for several years visited various specialists. In connection with a similar clinical picture, multi-organ damage, differential diagnosis was performed between systemic vasculitis (granulomatosis with polyangiitis) and scarring pemphigoid.The mucous membrane of the mouth and nose is involved in the pathological process with granulomatosis with polyangiitis in the form of ulcerative defects, which subsequently lead to deformation of the nose. The danger with this systemic vasculitis is renal damage with the development of nephritis, renal failure. With scarring pemphigoid, eye damage is typical. In granulomatosis with polyangiitis, damage to the organ of vision is also sometimes possible, but mainly in the form of an orbit pseudotumor. Despite the fact that treatment for both forms of pathology involves the use of glucocorticoids and cytostatics, with a scarring pemphigoid, the main care is provided by dermatologists and ophthalmologists, while the diagnosis and treatment of systemic vasculitis is the task of rheumatologists. One of the criteria for a scarring pemphigoid is loss of vision. However, in this case, it was possible to establish a diagnosis, obtain the first positive results of therapy before the patient shows signs of disability. So, there is a hope for the possibility of preserving vision and a favorable outcome. The rarity of the disease and its poor knowledge, difficulties in diagnosis and the absence of certain standards of therapy, this diagnosis requires more attention from the specialists.

P186 Efficacy and safety of rituximab in the treatment of systemic vasculitis: experience at a single centre

Abstract Background Rituximab is a monoclonal chimeric antibody targeting the mature B cell molecule CD20, expressed on the cell surface. It is licenced and widely used in the treatment of autoimmune diseases, including the ANCA associated vasculitides and rheumatoid arthritis. The efficacy and safety of rituximab in rare diseases requires ongoing appraisal. Methods We interrogated the records of 62 consecutive patients treated with rituximab for small vessel systemic vasculitis at our unit over the last 3 years, using a contemporaneously maintained central database, as well as individual electronic patient records. Results The patient demographic data, and main results are presented in Table 1. 31 (50%) of the patients treated with rituximab were female, and the indication for treatment in most cases was ANCA associated vasculitis (77.4%). After a mean follow up period of 2.04 years, the mean reduction in BVAS was 1.64 (3.83). 5 severe adverse events were recorded, defined as death or hospitalisation potentially related to treatment with rituximab. 3 patients died of respiratory sepsis, 1 experienced a wound infection, and 1 experienced an ischaemic colon. Four patients were noted to have low immunoglobulins. Conclusion Rituximab is an effective treatment for many patients with systemic, small vessel vasculitis. Understanding the safety profile of this drug in the context of our cohort is challenging, given the significant morbidity associated with the underlying disease, as well as the age profile and concomitant immunosuppressive medications. Continued surveillance regarding efficacy and safety of rituximab in the small vessel systemic vasculitides remains invaluable. Disclosures C. Orr None. A. Verdiyeva None. N. Ahmad None. H. Ariff None. R. Luqmani None.

New Information for the Diagnosis and Treatment of Systemic Vasculitis

New Information for the Diagnosis and Treatment of Systemic Vasculitis

The modern therapy of systemic vasculitides: perspectives and challenges.

Systemic vasculitis is a heterogeneous group of inflammatory diseases, which are classified according to the diameter of the affected vessels. The treatment of systemic vasculitis is no longer empirical, because of increasing number of randomized clinical trials in this field. In recent years, there was a trend to limit the cumulative dose of glucocorticosteroids and immunosuppressive drugs, partially through biological drugs usage. However, biologic therapy is not always superior to combination of glucocorticosteroids and cytotoxic drugs. The efficacy of different biologic drugs varies in patients with different forms of systemic vasculitis, which creates the ground for personalized therapy of these diseases. Another serious problem is the absence of strict criteria to immunosuppressive therapy intensification, especially in vasculitis, affecting large vessels, due to the lack of reliable laboratory markers of disease activity. The article reviews modern approaches to the treatment of some types of systemic vasculitis, including ANCA-associated vasculitides, giant cell arteritis, Takayasu`s arteritis and cryoglobulinemic vasculitis.

Хвороба Кавасакі: особливості клінічної симптоматики та лікування

In this article the literature data on diagnosis verification and treatment of systemic vasculitis — Kawasaki disease (KD) in infants are analyzed. Features of clinical symptoms, diagnostics, treatment and follow&up of the 3&year child with the lack of a complete set of «classical» criteria of KD are given.

EXPERIENCE WITH EFFECTIVE COMBINED ANTI-B-CELL THERAPY WITH RITUXIMAB AND BELIMUMAB FOR REFRACTORY GRANULOMATOSIS WITH POLYANGIITIS (WEGENER'S) WITH SEVERE LUNG DAMAGE

Systemic vasculitis (SV) associated with antineutrophil cytoplasmic antibodies (ANCA) is characterized by severe multiple organ lesions with a poor prognosis. The successful introduction of standard therapy with cyclophosphamide (CP) and innovative anti-B-cell therapy with rituximab (RTM) for the treatment of ANCA SV gives no grounds to stop further searching for effective and safe therapy since about 10–15% of patients with ANCA SV are refractory to standard therapy with CP; after the latter, approximately 40% of patients develop recurrences, and granulomatous inflammation in the respiratory organs in granulomatosis with polyangiitis (GPA) can be resistant to RTM treatment, especially following its single cycle. There is increasing evidence that the efficiency of anti-B-cell therapy can be enhanced by adding belimumab (BLM). The paper describes a clinical case of effective sequential combined anti-B-cell therapy with BLM and RTM for remission induction in a female patient who has GPA with severe granulomatous lung injury refractory to previous therapy with CP (a total dose of 6.2 g) and a single cycle of therapy with RTM (a total dose of 2.6 g). BLM was used 12 months after RTM administration because there were no positive changes in lung injury. At 12 months after initiations of treatment with BLM (800 mg twice at a weekly interval, then 800 mg monthly), there was a substantial reduction in the lung parenchymal foci, as evidenced by multislice spiral computed tomography (MSCT); and the treatment was continued for another 6 months, thereafter discontinued due to the occurrence of ulcerative stomatitis. After its relief, RTM was again given at reduced dose cycles of 500 mg every 6 months; lung MSCT showed further improvement and remission achieved. BLM may be effective in treating the GPA patients who are refractory to CP and have an insufficient response to RMT treatment. Combined anti-B-cell therapy aimed at depleting SD20+ B-cells and at blocking BAFF may be a promising area for the treatment of patients with ANCA SV.

State of the art in the treatment of systemic vasculitides.

Anti-neutrophil cytoplasm antibodies (ANCA) are associated with small vessel vasculitides (AASV) affecting the lungs and kidneys. Structured clinical assessment using the Birmingham Vasculitis Activity Score and Vasculitis Damage Index should form the basis of a treatment plan and be used to document progress, including relapse. Severe disease with organ or life threatening manifestations needs cyclophosphamide or rituximab, plus high dose glucocorticoids, followed by lower dose steroid plus azathioprine, or methotrexate. Additional plasmapheresis is effective for very severe disease, reducing dialysis dependence from 60 to 40% in the first year, but with no effect on mortality or long-term renal function, probably due to established renal damage. In milder forms of ANCA-associated vasculitis, methotrexate, leflunomide, or mycophenolate mofetil are effective. Mortality depends on initial severity: 25% in patients with renal failure or severe lung hemorrhage; 6% for generalized non-life threatening AASV but rising to 30–40% at 5 years. Mortality from GPA is four times higher than the background population. Early deaths are due to active vasculitis and infection. Subsequent deaths are more often due to cardiovascular events, infection, and cancer. We need to improve the long-term outcome, by controlling disease activity but also preventing damage and drug toxicity. By contrast, in large vessel vasculitis where mortality is much less but morbidity potentially greater, such as giant cell arteritis (GCA) and Takayasu arteritis, therapeutic options are limited. High dose glucocorticoid results in significant toxicity in over 80%. Advances in understanding the biology of the vasculitides are improving therapies. Novel, mechanism based therapies such as rituximab in AASV, mepolizumab in eosinophilic granulomatosis with polyangiitis, and tocilizumab in GCA, but the lack of reliable biomarkers remains a challenge to progress in these chronic relapsing diseases.

AB0760 Role of oral cyclophosphamide in the treatment of giant cell arteritis

BackgroundGlucocorticoids (GC)-related adverse events greatly contribute to the outcome in giant cell arteritis (GCA). There is limited evidence of the efficacy of some DMARDs as steroid-sparing agents in GCA. CYC...

ARTERIAL HYPERTENSION IN SYSTEMIC VASCULITIS: CLINICAL FEATURES AND PRINCIPLES OF PATHOGENETIC THERAPY. PART II. POSSIBILITIES OF OPTIMIZING OF ANTIHYPERTENSIVE TREATMENT

The article deals with the problem of arterial hypertension in systemic vasculitis. Data on the principles of antihypertensive treatment of systemic vasculitis are presented. The possibilities of pharmacotherapy and surgical treatment of these diseases are discussed separately.

Anti-Tumor Necrosis Factor Blocking Agents in the Treatment of Systemic Vasculitis

Anti-Tumor Necrosis Factor Blocking Agents in the Treatment of Systemic Vasculitis

Evidencias sobre la eficacia de los tratamientos biológicos en las vasculitis sistémicas

In recent decades, there has been a breakthrough in the treatment of systemic vasculitis, although substantial morbidity and mortality are still associated with these diseases, often related to immunosuppressive therapy. The success of biologic therapy in rheumatoid arthritis and other autoimmune diseases has led to research into these agents in systemic vasculitis. Anti-tumor necrosis factor (TNF) agents have proven useful in the treatment of Takayasu arteritis refractory to conventional treatment but there is no evidence of their effectiveness in other types of vasculitis. Anti-CD20 therapy (rituximab) has proven effective in ANCA vasculitis refractory to cyclophosphamide. Two recently published clinical trials have shown that rituximab is not inferior to cyclophosphamide as induction therapy of remission in ANCA Vasculitis, so in the future, could be considered a first line treatment in these patients.

European League Against Rheumatism/European Vasculitis Study Group recommendations for the management of vasculitis

To discuss the European League Against Rheumatism recommendations in the management of primary systemic vasculitis. Important developments in the classification and treatment of systemic vasculitis have led the European League Against Rheumatism to publish recommendations in the diagnosis, treatment and monitoring of the small, medium and large-vessel vasculitides. These recommendations resulted from a combination of evidence from systematic analysis of selected studies and the experience of experts in vasculitis when data were not available. The purpose of formulating clinical recommendations is to improve quality of care and guide the clinician inexperienced with vasculitis. Nevertheless, patients with vasculitis should be managed by a vasculitis expert whenever possible. As our understanding of this rare and complex group of diseases advances, novel therapeutic options are being developed.

Targeted Biologic Approaches to the Treatment of Systemic Vasculitis

The introduction of biological agents in the treatment of systemic vasculitis offers the promise of targeted therapy with greater efficacy and fewer side effects than conventional treatments. In this paper, we review the rationale for biological strategies in vasculitis and discuss the results of clinical studies to date. The biotherapies discussed include immune-cell-depleting agents, both B- and T-cell targeted; costimulatory blockade; and cytokine blockade. Although most of these agents remain unproven until ongoing randomized clinical trials are complete, their introduction heralds a new era of vasculitis treatment and has provided novel insights into disease pathogenesis.