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.

Patterns of immunosuppressive drug use during pregnancy in women with systemic vasculitis: A nationwide population-based cohort study.

OBJECTIVE: Systemic vasculitis (SV) rarely affects women of childbearing age and only small series have been reported to date in pregnant patients. The discovery of an unplanned pregnancy can be an urgent cause for modifying treatments. This study aimed to describe immunosuppressive drugs use before, during and after pregnancy in women with SV. METHODS: We conducted a cohort study using the French nationwide claims database. We included all women with SV being pregnant between 2013 and 2018. Exposure of interest was defined as exposure to oral systemic or injectable immunosuppressive drug identified using out-hospital reimbursement data and in-hospital reimbursement for expensive drugs. RESULTS: Of 3,246,454 pregnancies, 649 pregnancies were observed in 606 women with SV. Immunosuppressant and glucocorticoids use decreased before pregnancy and then increased after pregnancy (48.4%, 40.7%, 50.4%, respectively before, during, after). Prevalence of glucocorticoids use was broadly stable during pregnancy from 27.9% to 27.6% and 23.7% in the 1st, 2nd and 3rd trimesters, respectively, with a daily dose of about 5 mg. The number of patients treated with non-recommended immunosuppressant during pregnancy gradually decreased before pregnancy and then increased after delivery, whereas proportion of systemic vasculitis flare, estimated from the glucocorticoids daily dose, did not increase significantly during pregnancy. CONCLUSION: Immunosuppressants and glucocorticoids use decreased before pregnancy and remained stable throughout, suggesting a vasculitis control during this period. Our findings support the importance of pre-conceptional consultations to review medications, and switch not-recommended and teratogenic medications to drugs considered being safe during pregnancy.

The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.

One year in review 2021: systemic vasculitis.

Large- and small-vessel vasculitis are complex potentially life-threatening systemic autoimmune diseases that have recently been subjected to considerable immunologic and clinical research. Following the other reviews of this series, here we aim to summarise some of the most significant studies that have been recently published on the pathogenesis, clinical features and novel treatments of systemic vasculitis.

A single center survey study of systemic vasculitis and COVID-19 during the first months of pandemic

Introduction: COVID-19 pandemic created concerns among patients receiving immunosuppressive therapy. Frequency of COVID-19 and impact of lockdown on treatment compliance in patients with vasculitis are largely unknown. Patients and method: Patients with ANCA-associated and large vessel vasculitis that have been followed-up in our clinic were contacted by phone and a questionnaire containing home isolation status, treatment adherence and history of COVID -19 between March 1st and June 30th, 2020 was applied. Results: The survey was applied to 103 patients (F/M: 59/44, mean age: 53.2±12.5). Thirty-three (32%) patients didn?t attend at least one appointment; 98(95.1%) noted that they spent 3 months in home isolation. Five patients (4.8%) received immunosuppressives irregularly and 3(2.9%) developed symptoms due to undertreatment. Four (3.9%) patients admitted to hospital with a suspicion of COVID-19, but none of them had positive PCR or suggestive findings by imaging. COVID-19 diagnosed in a patient with granulomatosis with polyangiitis during hospitalization for disease flare and she died despite treatment. Discussion: Frequency of COVID-19 was low in patients with vasculitis in our single center cohort. Although outpatient appointments were postponed in one-third of our patients, high compliance with treatment and isolation rules ensured patients with vasculitis overcome this period with minimal morbidity and mortality.

Risk Factors for Severe Outcomes in Patients With Systemic Vasculitis and COVID-19: A Binational, Registry-Based Cohort Study.

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID-19. We undertook this study to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. RESULTS: The cohort included 65 patients with systemic vasculitis who developed COVID-19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1-14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9-38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision-making relating to the risk of severe COVID-19 in this vulnerable patient group.

Combination rituximab and intravenous immunoglobulin for treatment of refractory vasculitic neuropathy: a case series.

OBJECTIVE: Limited evidence exists to guide treatment of refractory vasculitic neuropathy. While rituximab (RTX) and IVIG have both been proposed as individual treatment options for these patients, combination therapy has never been reported. METHODS: Written informed consent was obtained from three patients with refractory vasculitic neuropathy who were treated with combination RTX and IVIG. Their electronic medical records were reviewed and clinical and functional outcomes were reported. RESULTS: Two male patients with non-systemic vasculitic neuropathy and one male patient with granulomatosis with polyangiitis were treated with combination RTX and IVIG therapy. All three patients demonstrated clinical improvement with at least partial functional recovery and a reduction in corticosteroid dose. This combination was generally well tolerated. CONCLUSIONS: Combination RTX and IVIG therapy may be a safe and effective treatment option for patients with refractory vasculitic neuropathy. Further studies are needed to better characterize the risks and benefits of this combination.

Eficácia e segurança de Rituximabe comparado a outras drogas no tratamento de vasculites sistêmicas: revisão rápida de evidências / Efficacy and safety of Rituximab compared to other drugs in the treatment of systemic vasculitides: rapid response review of evidence

Objetivo: descrever as evidências disponíveis na literatura científica sobre eficácia e segurança do rituximabe comparado a diferentes tratamentos. Materiais e métodos: é uma revisão rápida de evidências científicas para tomada de decisão informada por evidências em políticas e práticas de saúde. Conclusão: o Rituximabe tem eficácia e segurança similares à da Ciclofosfamida, para terapia de indução de remissão e para manutenção da remissão e, para pacientes com doença recidivante, o Rituximabe é mais eficaz que a Ciclofosfamida para manter a remissão. Para terapia de manutenção, Rituximabe é mais eficaz que Azatioprina, com perfil de segurança similar. Diferentes regimes de dosagem do Rituximabe tem eficácia e segurança similar para terapia de manutenção. O Infliximabe parece ser superior ao Rituximabe nos desfechos de eficácia (indução e manutenção da remissão).

Objective: to describe the evidence available in the scientific literature on the efficacy and safety of rituximab compared to different treatments. Materials and Methods: is a rapid review of scientific evidence for evidence-informed decision making in health policy and practice. Conclusion: Rituximab has similar efficacy and safety to Cyclophosphamide, for remission induction therapy and for maintenance of remission, and for patients with relapsing disease, Rituximab is more effective than Cyclophosphamide in maintaining remission. For maintenance therapy, Rituximab is more effective than Azathioprine, with a similar safety profile. Different dosing regimens of Rituximab have similar efficacy and safety for maintenance therapy. Infliximab appears to be superior to Rituximab in efficacy outcomes (induction and maintenance of remission).

Síndrome de Behçet ou úlcera de Lipschütz: desafio diagnóstico / Behçet's syndrome or Lipschütz ulcer: diagnostic challenge

A ocorrência de úlceras genitais em adolescentes e mulheres jovens tem impacto emocional para as pacientes e seus familiares, pela frequente associação com uma possível etiologia de transmissão sexual. Porém, úlcera de Lipschütz e síndrome de Behçet não têm etiologia infecciosa e devem ser lembradas como possíveis diagnósticos diferenciais. O diagnóstico dessas duas patologias é clínico e pode ser desafiador. Dessa forma, foi realizada uma revisão na literatura com o objetivo de comparar as duas entidades. A úlcera de Lipschütz é causada por uma vasculite local e caracteriza-se pelo surgimento súbito de úlceras na vulva ou vagina inferior. Já a doença de Behçet é causada por vasculite sistêmica, com episódios de remissão e exacerbação, que pode envolver quase todos os sistemas orgânicos. Em ambos os casos, é essencial o referenciamento para reumatologia. O tratamento objetiva suprimir exacerbações, controlar a dor e prevenir infecção secundária.(AU)

The occurrence of genital ulcers in adolescents and young women have an emotional impact for the patient and their families, due to the frequent association of its etiology with a sexually transmitted disease. However, Lipschütz ulcer and Behçet's syndrome do not have an infectious etiology and should be remembered as a possible differential diagnoses. As the diagnosis of these two pathologies is clinical and can be challenging, a review of literature was carried out. The objective of this review of literature was to compare both diseases. Lipschütz ulcer is caused by local vasculitis and is characterized by the sudden appearance of ulcers in the vulva or lower vagina. Behçet's syndrome is caused by systemic vasculitis, with episodes of remission and exacerbation, which can affect almost all organ systems. In both cases, referral to rheumatology is essential. Treatment aims to suppress exacerbations, control pain and prevent secondary infection.(AU)

Systemic vasculitis successfully treated with decitabine in a high-risk myelodysplastic syndrome patient: a case report and literature review.

Aim: Epidemiological studies have reported the association between myelodysplastic syndrome (MDS) and autoimmune diseases (AIDs). Immune dysregulation appears as the common driving force between MDS and AIDs pathogenesis. Low-dose hypomethylating agents might suppress tumor growth and regulate immune balance via its epi-immunomodulatory role. Materials & methods: A high-risk MDS patient presented with systemic vasculitis and was successfully treated with ultra-low-dose decitabine (7 mg/m2/d for 5 days). Results: He achieved complete remission of both MDS and AIDs after two cycles of decitabine treatment, and his overall survival duration was 45 months. Conclusion: Future studies should assess the application of ultra-low-dose decitabine among some high-risk MDS patients, especially among those with comorbid AIDs or in cases warranting the prevention of decitabine-mediated myelosuppression.

Management of Primary Small-Vessel Vasculitis.

Small-vessel vasculitides (SVV) are a group of disorders that occur due to primarily systemic inflammation or as sequelae of an infection, malignancy, or other rheumatic disease. Arising in any organ including the skin, the clinical features of SVV encompass a variety of manifestations. A comprehensive diagnostic assessment should be performed as management protocols widely differ. Although rare, physicians should be familiar with the common types of SVV to ensure prompt management and prevention of severe, life-threatening end-organ damage. Given the variable manifestations and associated etiologies of SVV, the following review aims to discuss the pathogenesis of more prevalent SVVs, highlight distinguishing features to aid in patient evaluation and diagnosis, and examine evidence-based management options for treatment and care.

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.

B artonella endocarditis masquerading as systemic vasculitis with rapidly progressive glomerulonephritis (aka 'Löhlein nephritis').

Bartonella species are fastidious, Gram-negative aerobic rods and a well-recognised pathogen responsible for culture-negative endocarditis. The histopathological appearance of glomerulonephritis (GN) caused by Bartonella endocarditis may include a pauci-immune GN similar to that usually seen in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Herein, we present an unusual case report of Bartonella endocarditis masquerading as ANCA-positive vasculitis, with crescentic GN. A 66-year-old woman, who had undergone aortic valve replacement 2 years prior to admission, presented with confusion and loss of vision in her right nasal field. Following an extensive diagnostic evaluation, the main findings were right central retinal artery occlusion, ground-glass appearance on chest CT and ANCA-positive, anti PR-3 negative, rapidly progressive GN. The patient was scheduled to start treatment with rituximab for presumed ANCA-positive GN, when a positive serological test for Bartonella henselae was received. In view of this result, a diagnosis of endocarditis was made, based on fulfilment of five Duke minor criteria, namely fever, predisposition, arterial emboli, immunological phenomena and serological evidence of active infection with an organism consistent with infective endocarditis. Immunosuppressive treatment was withheld and antibiotic treatment initiated. This case report emphasises the need for maintaining a high index of suspicion regarding the diagnosis of Bartonella infection, which might mimic ANCA-associated GN.

Early large vessel systemic vasculitis in adults.

Giant cell arteritis (GCA) is the most common vasculitis in individuals older than 50 years in Western countries. In addition to the typical pattern of cranial ischemic manifestations, large vessel vasculitis (LVV) involvement has emerged as a common feature of GCA. Patients with predominant LVV manifestations differ from those with the cranial pattern. They are usually affected at a younger age and often have nonspecific manifestations such as constitutional syndrome, fever of unknown origin, or refractory/atypical polymyalgia rheumatica (PMR). In these patients, cranial manifestations are often absent. Furthermore, patients with isolated PMR should be followed up because of the potential risk of severe vascular complications in the setting of an underlying GCA. Whereas temporal artery biopsy and/or color duplex ultrasound of the temporal arteries is useful for the diagnosis of cranial GCA, Doppler sonography of the subclavian and axillary arteries, fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography, magnetic resonance, and computed tomography-angiography are very useful to identify the presence of LVV, and they may play a potential role in the follow-up of these patients.

Advances in Therapies and Imaging for Systemic Vasculitis.

Vasculitis is a systemic disease characterized by immune-mediated injury of blood vessels. Current treatments for vasculitis, such as glucocorticoids and alkylating agents, are associated with significant side effects. Furthermore, the management of both small and large vessel vasculitis is challenging because of a lack of robust markers of disease activity. Recent research has advanced our understanding of the pathogenesis of both small and large vessel vasculitis, and this has led to the development of novel biologic therapies capable of targeting key cytokine and cellular effectors of the inflammatory cascade. In parallel, a diverse range of imaging modalities with the potential to monitor vessel inflammation are emerging. Continued expansion of combined structural and molecular imaging using positron emission tomography with computed tomography or magnetic resonance imaging may soon provide reliable longitudinal tracking of vascular inflammation. In addition, the emergence of radiotracers able to assess macrophage activation and immune checkpoint activity represents an exciting new frontier in imaging vascular inflammation. In the near future, these advances will allow more precise imaging of disease activity enabling clinicians to offer more targeted and individualized patient management.

Feasibility and Construct Validation of the Patient Reported Outcomes Measurement Information System in Systemic Vasculitis.

OBJECTIVE: The Patient Reported Outcome Measurement Information System (PROMIS) is a collection of item banks of self-reported health. This study assessed the feasibility and construct validity of using PROMIS instruments in vasculitis. METHODS: Data from a multicenter longitudinal cohort of subjects with systemic vasculitis were used. Instruments from 10 PROMIS item banks were selected with direct involvement of patients. Subjects completed PROMIS instruments using computer adaptive testing (CAT). The Medical Outcomes Study Short Form-36 (SF-36) was also administered. Cross-sectional construct validity was assessed by calculating correlations of PROMIS scores with SF-36 measures and physician and patient global scores for disease activity. Longitudinal construct validity was assessed by correlations of between-visit differences in PROMIS scores with differences in other measures. RESULTS: During the study period, 973 subjects came for 2306 study visits and the PROMIS collection was completed at 2276 (99%) of visits. The median time needed to complete each PROMIS instrument ranged from 40 to 55 s. PROMIS instruments correlated cross-sectionally with individual scales of the SF-36, most strongly with subscales of the SF-36 addressing the same domain as the PROMIS instrument. For example, PROMIS fatigue correlated with both the physical component score (PCS; r = -0.65) and with the mental component score (MCS; r = -0.54). PROMIS physical function correlated strongly with PCS (r = 0.81) but weakly with MCS (r = 0.29). Weaker correlations were observed longitudinally between change in PROMIS scores with change in PCS and MCS. CONCLUSION: Collection of data using CAT PROMIS instruments is feasible among patients with vasculitis and has some cross-sectional and longitudinal construct validity.

Pulmonary nodules in a patient with Giant Cell Arteritis.

Giant Cell Arteritis (GCA) is a common systemic vasculitis that involves medium and large arteries, most frequently extracranial branches of the carotid artery. Prompt diagnosis and treatment is essential to prevent devastating complications, such as blindness, stroke and aortic aneurysm or dissection. Typical symptoms include headache, temporal artery tenderness and jaw claudication. On rare occasions patients present with complaints related to pulmonary involvement. These include interstitial infiltration, pulmonary nodules, pleural effusion and pulmonary haemorrhage. The authors report the case of a 74-year-old man who presented with symptoms compatible with GCA confirmed by temporal biopsy, and pulmonary nodules. These lesions were biopsied and histological exam confirmed features compatible with systemic vasculitis. The lesions resolved after two months of steroid treatment. This case shows that we should be aware of atypical GCA manifestations.

Takayasu arteritis: A distinct syndrome of large vessel vasculitis: A view point by late Professor Paul Bacon.

Takayasu arteritis (TA), despite being classified as a large vessel vasculitis, has distinct genetic, pathological and clinical features as compared to giant cell arteritis. It is a rare disease seen more commonly in Asian countries. The challenge lies in assessing the degree of inflammation in a narrowed vessel and immunosuppressive therapy improves inflammatory features but is unable to open up an occluded vessel. It may have a positive effect on retarding further occlusion. Like antineutrophil cytoplasmic antibody-associated vasculitis, TA needs a collaborative effort to do randomized controlled therapy to provide benefit to patients.