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TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet's disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD., (© 2024. The Author(s).)

Head-to-head (H2H) studies enable the direct comparison of several alternative therapeutic approaches and thus provide the evidence-based foundation for the relative position of one treatment as compared to others for a specific indication. These trials constitute an important addition to placebo-controlled clinical trials. Among the controlled clinical trials not performed by the pharmaceutical industry, there are a relevant number of H2H trials for connective tissue diseases (CTDs) and vasculitides, particularly for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This article encompasses a review of the H2H trials for CTDs and vasculitides and discusses their relevance for current treatment algorithms. For SLE the H2H trials were predominantly performed for the treatment of lupus nephritis, demonstrating the impact of low-dose cyclophosphamide and mycophenolate as well as azathioprine for maintenance therapy. In recent H2H trials rituximab could be established as induction and maintenance therapy for AAV, which has now been incorporated into current treatment guidelines. Further comparative trials will be necessary in order to select the most effective and safest treatment for every patient, in the sense of personalized medicine., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: Extra-osseous (EO) manifestations are poorly characterized in chronic recurrent multifocal osteomyelitis (CRMO). This study aimed to further define the frequency, characteristics and treatment of EO events in CRMO and whether different phenotypes can be distinguished and benefit from special management., Methods: This multicentre retrospective study included CRMO patients followed in several paediatric rheumatology departments in France between 2015 and 2022. EO manifestations were defined as skin lesions, gastrointestinal manifestations, arthritis, enthesitis, sacroiliitis, uveitis, vasculitis and fever. At the last visit, the physician defined CRMO as active in the presence of clinical manifestations including both osseous and EO symptoms., Results: We included 133 patients; 87 (65.4%) were girls and the median age at first symptoms was 9.0 years (interquartile range 7.0-10.0). EO manifestations were described in 90 (67.7%) patients, with a predominance of skin lesions [n = 51/90 (56.7%)], followed by sacroiliitis [n = 38/90 (42.2%)], enthesitis [n = 21/90 (23.3%)], arthritis [n = 14/90 (15.6%)] and gastrointestinal manifestations [n = 6/90 (6.7%)]. The use of non-steroidal anti-inflammatory drugs and bisphosphonates did not differ by the presence or not of EO manifestations. Biologics were taken more frequently by patients with than without EO manifestations (P < 0.001); TNF inhibitors were used in 33 (36.7%) EO-positive patients. Under this treatment, 18 (54.5%) patients achieved complete remission of osseous and EO manifestations. At the last visit, more EO+ than EO- patients were on treatment (P = 0.009), with active disease in 58 (64.4%) patients., Conclusion: The analysis of EO manifestations in CRMO delineates two groups of patients in terms of severity and treatments used. Our study opens up new pathophysiological leads that may underlie the wide range of CRMO phenotypes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A 67-year-old man had taken the janus kinase (JAK) inhibitor, tofacitinib, for ulcerative colitis. He was referred to our department for a refractory ulcer on his lower leg. We suspected vasculitis and performed skin biopsy. Histopathological examination showed multinucleated giant cells in the epidermis and fibrinoid degeneration of small vessels in the upper dermis. Varicella zoster virus (VZV) DNA was detected by polymerase chain reaction and we diagnosed the patient with atypical vasculitis-like herpes zoster. The patient was treated with oral valacyclovir, but the rash persisted and took 2 months to heal. Immunostaining using anti-VZV antibody was positive mainly in epidermal keratinocytes, but was also observed to be positive in cells in the dermis. We further performed RNA in situ hybridization using a VZV ORF9 mRNA probe and clearly showed that the distribution of VZV mRNA extended into the dermis, including the dermal vessel walls and the eccrine sweat glands as well as the epidermis. The internal administration of JAK inhibitors may induce regional widespread VZV infection including vessels and involved in the formation of prolonged vasculitis-like manifestation. RNA in situ hybridization can be a potent tool for detecting the spread of VZV infection in the skin., (© 2024 Japanese Dermatological Association.)

Background: The activation of innate immunity may be involved in the development of Candida albicans-induced murine vasculitis, which resembles Kawasaki disease (KD) vasculitis. This study aimed to histologically clarify the time course of the development of vasculitis in this model in detail and to estimate the potential role of spleen tyrosine kinase (Syk) inhibitors in KD vasculitis., Methods and Results: DBA/2 male mice were intraperitoneally injected with a vasculitis-inducing substance and treated with a Syk inhibitor (R788 or GS-9973). Systemic vasculitis, especially in the aortic annulus area, was histologically evaluated. Regarding lesions in the aortic annulus area, some mice in the untreated control group already showed initiation of vasculitis 1 day after the final injection of a vasculitis-inducing substance. The vasculitis expanded over time. Inflammation occurred more frequently at the aortic root than at the coronary artery. The distribution of inflammatory cells was limited to the intima, intima plus adventitia, or all layers. In the Syk inhibitor-treated groups, only one mouse had vasculitis at all observation periods. The severity and area of the vasculitis were reduced by both Syk inhibitors., Conclusion: Candida albicans-induced murine vasculitis may occur within 1 day after the injection of a vasculitis-inducing substance. Additionally, Syk inhibitors suppress murine vasculitis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Mailuoning oral liquid (MLN O), one traditional Chinese patent medicine, has a good therapeutic effect on thromboangiitis obliterans (TAO) in clinical practice. However, the underlying mechanism remains unclear., Aim of the Study: This study aimed to explore the effects and potential mechanisms of MLN O against TAO based on network pharmacology and experimental verification., Materials and Methods: Network pharmacology was used to identify the intersectional targets and signaling pathways of MLN O and TAO. In vivo, the TAO model was established by injecting sodium laurate and dihydrotestosterone (DHT) into the femoral arteries of Wistar rats. Rats were given the indicated drugs by intragastric administration (i.g.), intravenous injection (i.v.), or subcutaneous injection (s.c.) per day for 21 days since a week before surgery. In vitro, HUVECs, RAW264.7, and THP-1 cells were stimulated by LPS and DHT to simulate the pathological changes of TAO. The anti-inflammatory, anticoagulant, and immunomodulatory effects of MLN O were evaluated by histological observation, blood biochemical indexes detection, H&E staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, western blotting and immunofluorescence assays. Furthermore, the vascular ring test was applied to explore the vasodilatory activity of MLN O., Results: MLN O significantly improved the pathological signs in TAO rats through its excellent anti-inflammatory, anticoagulant, immunomodulatory, and vasodilatory effects. Specifically, MLN O alleviated the gangrene and reduced the thrombosis in TAO rats, meanwhile, suppressed the expressions of inflammatory factors and clotting factors, which is related to the inactivations of cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways. However, the superphysiological dose of DHT deteriorated the pathological development of TAO in vitro and in vivo. Moreover, the results of network pharmacology are consistent with the experimental verification., Conclusion: Collectively, this study indicates for the first time that MLN O could alleviate TAO by inhibiting cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways, which sheds light on a novel clinical therapeutic strategy for TAO., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy., Methods: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up., Results: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up., Conclusion: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objectives: This case series reports clinical features and outcome of four patients with non-systemic vasculitic neuropathy (NSVN) treated with the anti-CD20 agent rituximab., Methods: Clinical, electrophysiological and biopsy data were retrospectively obtained and evaluated. Only patients with pathological definite or probable NSVN were included. Extensive clinical and laboratory work-up excluded systemic vasculitis. Follow-up data for at least 12 months and up to five years is provided. Outcome of the patients was assessed using the MRC-Sum Score, Prineas Score and Neurological Symptom Score., Results: Two of four patients treated with rituximab achieved disease remission and one patient remained stable under anti-CD20 therapy after a required treatment switch due to toxic side effects of cyclophosphamide. One patient deteriorated under rituximab induction. Rituximab was well tolerated in all patients., Discussion: Anti-CD20 therapy might be an alternative in NSVN patients requiring further treatment escalation or treatment switch due to side effects of corticosteroids or cyclophosphamide., (© 2024. The Author(s).)

In rare instances, patients with SLE may exhibit atypical clinical manifestations, such as Hypocomplementemic Urticarial Vasculitis, which can pose diagnostic challenges. Here, we present a case report of a 28-year-old female with a history of SLE with lupus nephritis clase IV who developed HUV-like symptoms, ultimately leading to a diagnosis of C1q Vasculitis. This case underscores the importance of considering C1q Vasculitis in SLE patients presenting with HUV-like features and highlights Rituximab as a promising therapeutic option for managing this rare condition., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

IgA nephropathy (IgAN) is a fairly common association with alcoholic liver disease. However, IgA vasculitis (IgAV) is quite an uncommon association with alcoholic liver cirrhosis and only a handful of cases have been reported in literature. Secondary IgAN usually presents in a docile manner, progressing slowly in about 5-25 years. It is usually responsive to steroid therapy, very rarely progressing to End-Stage Renal Disease. Here, we present a man in his late 50s, a known hypertensive and alcohol related liver-cirrhotic, who presented to our hospital with rash and rapidly progressive renal failure (RPRF). He was diagnosed with IgA nephritis with IgA vasculitis (IgAVN). His diagnosis was confirmed with skin and renal biopsy. He was started on renal replacement therapy for his renal failure and began oral steroid therapy. After administration of steroid therapy for 6 months, the patient recovered and was dialysis independent with stable renal parameters., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Background: Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk., Methods: In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR., Results: We studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms., Conclusions: Both treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT., Trial Registration: ClinicalTrials.gov ID NCT02374021., (© 2024. The Author(s).)

A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment of HCV and its sequelae are used to be predominantly based on Interferon (IFN). However, this was associated with significant adverse events as a result of its immunostimulant capabilities. Since their introduction, the directly acting antiviral drugs (DAAs), have become the standard of care to treat of HCV and its complications including mixed cryoglobulinemic vasculitis (MCV). In spite of achieving sustained viral response (SVR), there appeared many reports describing unwelcome complications such as hepatocellular and hematological malignancies as well as relapses. Prolonged inflammation induced by a multitude of factors, can lead to DNA damage and affects BAFF and APRIL, which serve as markers of B-cell proliferation. We compared, head-to-head, three antiviral protocols for HCV-MCV treatment As regards the treatment response and relapse, levels of BAFF and APRIL among pegylated interferon α-based and free regimens (Sofosbuvir + Ribavirin; SOF-RIBA, Sofosbuvir + Daclatasvir; SOF-DACLA). Regarding clinical response HCV-MCV and SVR; no significant differences could be identified among the 3 different treatment protocols, and this was also independent form using IFN. We found no significant differences between IFN-based and free regimens DNA damage, markers of DNA repair, or levels of BAFF and APRIL. However, individualized drug-to-drug comparisons showed many differences. Those who were treated with IFN-based protocol showed decreased levels of DNA damage, while the other two IFN-free groups showed increased DNA damage, being the worst in SOF-DACLA group. There were increased levels of BAFF through follow-up periods in the 3 protocols being the best in SOF-DACLA group (decreased at 24 weeks). In SOF-RIBA, CGs relapsed significantly during the follow-up period. None of our patients who were treated with IFN-based protocol had significant clinico-laboratory relapse. Those who received IFN-free DAAs showed a statistically significant relapse of constitutional manifestations. Our findings suggest that IFN-based protocols are effective in treating HCV-MCV similar to IFN-free protocols. They showed lower levels of DNA damage and repair. We believe that our findings may offer an explanation for the process of lymphoproliferation, occurrence of malignancies, and relapses by shedding light on such possible mechanisms., (© 2024. The Author(s).)

A woman in her late 30s presented with sudden diminution of vision, redness and pain in the right eye (OD) of 10 days' duration. Best corrected visual acuity (BCVA) was 20/160 in OD and 20/20 in the left eye (OS). Anterior segment of OD showed keratic precipitates, flare 3+, cells 2+ and a festooned pupil. Vitreous haze and cells were seen in OD. Frosted branch angiitis (FBA) was seen in all quadrants in OD and old Toxoplasma scar was seen in both eyes. Serum toxoplasma immunoglobulin G (IgG) was positive and IgM negative, and PCR of an aqueous humour sample was negative for Toxoplasma She was diagnosed with toxoplasa retinochoroiditis in OD and treated with intravitreal clindamycin injections, oral anti- Toxoplasma antibiotics and steroids. Three months later, her BCVA in OD was 20/40 with resolving inflammation. She presented 2 months later with a new focus of retinochoroiditis without FBA and an old Toxoplasma scar., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

A 29-year-old Caucasian woman presented with a 3-month history of bilateral lower limb swelling with painful erythematous nodules on shins without ulceration. She had been taking minocycline for acne vulgaris for 3 years. Biochemical investigations showed deranged liver function test with positive ANA and mixed antinuclear factor (ANF) pattern. A skin biopsy was in keeping with a diagnosis of nodular vasculitis. Her skin lesions and liver function test improved within 3 months of stopping the minocycline treatment. This case report raises the awareness that minocycline could be a potential cause of nodular vasculitis, patients on minocycline should be closely monitored and minocycline should ideally not be prescribed for more than 12 weeks, given the possible adverse effects., (© 2023 Australasian College of Dermatologists.)

Membranous nephropathy has been associated with demyelinating polyneuropathies and antiglomerular membrane disease; however, an association with vasculitic neuropathy has not been described. This case describes a patient with biopsy-proven idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis, who presented with lower limb microvascular ischaemia, peripheral neuropathy and active urinary sediment. Her extensive non-invasive screening for immunological disease and radiological investigations for occult malignancy were unremarkable. The patient received intravenous methylprednisolone and intravenous rituximab induction therapy resulting in complete remission of both the idiopathic membranous nephropathy and small vessel vasculitis at 7 months post treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cryoglobulins are immunoglobulins that precipitate in cold conditions. Type I cryoglobulinemic vasculitis is associated with hematological malignancies. We herein report a case of steroid-resistant type 1 cryoglobulinemic vasculitis associated with monoclonal gammopathy of undetermined significance (MGUS) in a 47-year-old woman. By immunofixation of cryoglobulin, we found that the main component of cryoglobulin was the M protein due to MGUS, so treatment of MGUS was needed. Bortezomib+dexamethasone therapy resulted in a rapid decrease in cryoglobulin and improvement in the symptoms of cryoglobulinemic vasculitis. In refractory type I cryoglobulinemic vasculitis, treatment of the underlying gammaglobulinopathy should be considered.

Background/objectives: To describe frequency and type of ocular manifestations in patients with cryoglobulinemic vasculitis (CV), as well as management approaches and outcomes., Subjects/methods: This was a retrospective, observational, cohort study of patients who were diagnosed with CV at a single center and regularly underwent a comprehensive ocular assessment., Results: Ophthalmologic manifestations were recorded in 16 patients (28%). The diagnoses included dry eye disease and primary Sjögren syndrome in 5 and 2 patients, respectively; peripheral ulcerative keratitis and anterior scleritis in 1 patient each; hyperviscosity syndrome and hypertensive retinopathy in 2 patients each; and Purtscher- like retinopathy in 3 patients. Twelve patients (75%) were anti-HCV/HCV RNA-positive, 11 of whom achieved a sustained virologic response (SVR) following treatment with interferon-α2b plus ribavirin or direct-acting antivirals. All patients were treated with ocular lubricants. Systemic therapeutic measures, including glucocorticoids, immunosuppressive and biologic agents, induced the disappearance or ≥50% reduction of cryoglobulins and major signs of vasculitis in 11 patients (68.7%). In the remaining 5 patients (31.3%), cryoglobulins and CV manifestations remained unchanged or decreased by <50%. The corresponding ophthalmologic assessment showed a variable degree of improvement in the ocular symptoms in all but 2 patients (87.5%). The best corrected visual acuity following treatment improved in 26 eyes, was unchanged in 3 eyes, and worsened in 3 eyes., Conclusions: Eye involvement is not a rare event in CV patients. A timely diagnosis and the correct employment of the available therapeutic measures may result in a favorable outcome of the ocular and extra-ocular manifestations., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment., Methods: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan., Results: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFβ receptors. Measurement of the inflammatory cytokines IL-1β, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan., Conclusions: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

Purpose of Review: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV., Recent Findings: The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome., Summary: Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Kawasaki disease (KD) is an acute self-limiting vasculitis, and it is the most common cause of acquired heart disease in children under 5 years old. One of the improvement goals in pediatric quality control work for the year 2023, as announced by the National Health Commission, is to reduce the incidence of cardiac events and KD-related mortality in children with KD. In order to standardize the diagnosis, treatment, and long-term management practices of KD in China, and effectively prevent and reduce the incidence of coronary artery lesions and long-term adverse effects, the guideline working group followed the principles and methods outlined by the World Health Organization and referenced existing evidence and experiences to develop the "Evidence-based guidelines for the diagnosis and treatment of Kawasaki disease in children in China (2023)". The guidelines address the clinical questions regarding the classification and definition of KD, diagnosis of different types of KD, treatment during the acute phase of KD, application of echocardiography in identifying complications of KD, and management of KD combined with macrophage activation syndrome. Based on the best evidence and expert consensus, 20 recommendations were formulated, aiming to provide guidance and decision-making basis for healthcare professionals in the diagnosis and treatment of KD in children.

Immunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4-12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition. Key Points • Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations. • The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis., (© 2023. The Author(s).)

Objectives: To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups., Methods: A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup ( n =30), the >12 years MMF subgroup ( n =15), the ≤12 years CTX subgroup ( n =71), and the >12 years CTX subgroup ( n =19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions., Results: There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment ( P >0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment ( P >0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment ( P <0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup ( P <0.05)., Conclusions: The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Vasculitis, involving any levels of vessels throughout the body, has variable nonspecific clinical presentation and complicated classification, hence, the diagnose is difficult. The liver is not the major organ involved, so it is prone to overlook vasculitis-associated liver injuries. The main manifestations of vasculitis involving the liver include abnormal liver biochemistry test (mainly increase of cholestatic liver enzymes), portal hypertension, and hepatic occupying lesions. Treatment principles are primarily directed at systemic immunosuppressive therapy for vasculitis. This review summarized the classification of vasculitis, major presentations of liver involvement in vasculitis, and the principles of treatment, to improve the awareness of the rare vascular diseases.

Introduction: We describe a systemic neoplastic cryoglobulinemic vasculitis presenting as a large vessel occlusion (LVO) syndrome. We focus on a rare presentation of a rare condition., Case Report: A 68-year-old man was admitted to the Stroke Unit of Padova with a right middle cerebral artery syndrome. A cerebrovascular event was suspected and protocol for revascularization treatment was performed. Neuroimaging provided no evidence for infarcted tissue or medium-large vascular occlusion but hypothesized a vasculitic involvement of the small vessels of the right hemisphere. Further diagnostics demonstrated a microangiopathic involvement of the heart, kidneys, and lungs. Blood tests showed circulating cryoglobulins and further hematological investigation identified a chronic lymphatic leukemia-like lymphoproliferative disorder. High-dose steroid therapy improved the patient's clinical status and no neurological symptoms remained at discharge., Conclusion: We discuss the clinical-radiologic presentation of a small vessel vasculitis that mimics an LVO stroke. This case focuses on the relevance of concomitant multiorgan manifestations in the hyper-acute evaluation of LVO stroke, suggesting the clinical neurologist should consider alternative etiologies as these could provide important clinical implications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Central precocious puberty (CPP) is defined as the appearance of secondary sexual signs in girls younger than eight years of age or the onset of menarche before the age of 10 years. Gonadotropin-releasing hormone analogs (GnRHa) are the most effective therapy in CPP. Drug-induced hypersensitivity vasculitis is an inflammation of blood vessels, which may be due to the use of a number of pharmacologic agents. This case report describes drug-induced vasculitis in a girl being treated with Decapeptyl. A 7.25 year-old girl was admitted to Pediatric Endocrinology outpatients with premature breast development. She was diagnosed with CPP on the basis of physical examination and laboratory findings and tripoteline acetate (Decapeptyl ® ) treatment was initiated. She experienced multiple widespread skin rashes and mild abdominal pain with high temperature eight hours after the second dose of Decapeptyl. She was admitted to hospital with the diagnosis of drug-induced vasculitis and a single dose of intravenous methyl-prednisolone (1 mg/kg) and oral cetirizine was given. Her blood and urine analysis revealed no other organ involvement, other than skin. On the third day, the purpuric lesions began to resolve and had completely disappeared by the sixth day. Her treatment for CPP was switched to Depot Leuprolide acetate and she continued her treatment for two years uneventfully. To the best of our knowledge, this is the first report of a child with CPP experiencing drug-induced vasculitis due to tripotelin injection. Effective treatment may be continued by switching to an alternative gonadotropin releasing hormone analog.

Background: Immunoglobulin A vasculitis is a systemic form of vasculitis that predominantly affects children. Factor XIII activity is decreased in some cases, and several reports have shown an association between abdominal pain and decreased factor XIII activity. However, the clinical significance of decreased factor XIII activity in pediatric immunoglobulin A vasculitis has not been fully elucidated. This study aimed to identify the association between factor XIII activity and the clinical course of pediatric patients with immunoglobulin A vasculitis., Methods: Forty-four pediatric patients, admitted to Kita-Harima Medical Center with a clinical diagnosis of immunoglobulin A vasculitis between October 1, 2013 and September 30, 2022, were retrospectively reviewed, and 22 patients were analyzed. The patients' background characteristics and clinical course were compared between the normal and decreased factor XIII activity (<70%) groups., Results: The group with decreased factor XIII activity showed a significantly increased duration of hospitalization (14 [6-36] vs. 7 [5-13] days, p = 0.01), total glucocorticoid dose (prednisolone 22.7 [4.9-55.5] vs. 10.1 [3.4-19.6] mg/kg, p = 0.02), and duration of glucocorticoid administration (19 [4-85] vs. 10 [3-15] days, p = 0.03). Correlational analyses showed that these three parameters were negatively correlated with factor XIII activity., Conclusions: Factor XIII activity was negatively correlated with the duration of hospitalization, total glucocorticoid dose, and duration of glucocorticoid administration. Factor XIII activity is not only associated with abdominal symptoms but also may be a marker to predict the overall trajectory of acute-phase treatment in pediatric patients with immunoglobulin A vasculitis.

Background: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series., Objectives: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease., Methods: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs., Results: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole., Conclusion: Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality., (© 2023 Wiley-VCH GmbH.)

The coronavirus disease 2019 (COVID-19) pandemic has led to the emergence of multiple challenges in the care of patients with systemic rheumatic diseases. Patients with vasculitis represent a group of particular concern due to existing risk factors which include a higher burden of comorbidities and specific immunosuppressive therapies used for treatment. Vaccination and the use of other risk mitigation strategies are crucial for the care of these patients. This review provides an overview of existing evidence to contribute to the understanding and specific requirements of the treatment and management of patients with vasculitis during the time of COVID-19., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD)., Methods: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved., Results: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations., Conclusion: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions., Competing Interests: Declaration of Competing Interest A Marinho received consulting, speaker and advisory board fees from AbbVie, Lilly, MSD, Novartis, Pfizer and Roche, speaker fees from BMS and Janssen, consulting fees from Janssen and Takeda; and received support for attending meetings from AbbVie, Janssen, Novartis and Pfizer. J Delgado Alves received consulting, speaker and advisory board fees from AbbVie, Lilly and Novartis, and consulting fees from Pfizer. C Vasconcelos received advisory board fees from AstraZeneca, GSK, Janssen, Novartis, and Pfizer. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Human immunodeficiency virus (HIV) has a protean clinical picture, in rare instances manifesting as systemic autoimmune disorders such as vasculitides. HIV-induced autoimmune diseases often do not respond well to systemic immunosuppressive therapy. Opportunistic infections may occur in patients with either acquired immunodeficiency syndrome (AIDS) or heavy immunosuppressive treatment, and can further complicate the clinical presentation., Case Presentation: A patient presenting with immunoglobulin A (IgA) vasculitis (IgAV) with treatment-refractory purpuric skin rash and suspect intestinal vasculitis was discovered to have AIDS. HIV was the trigger of IgAV, and cytomegalovirus (CMV) colitis mimicked intestinal vasculitis. Antiretroviral treatment improved both CMV colitis and the control of the autoimmune disease., Conclusions: An autoimmune disease relapsing despite adequate immunosuppressive treatment and/or the presence of recurrent severe opportunistic infections may be clues to an underlying HIV infection., (© 2023. The Author(s).)

Glatiramer acetate is one of the oldest and safest disease modifying therapies used to treat relapsing-remitting multiple sclerosis. Urticarial vasculitis is a rare complication of treatment with glatiramer acetate, having been reported by only two others previously. Here, we describe a case of normocomplementemic urticarial vasculitis diagnosed on skin punch biopsy in a patient with multiple sclerosis treated with glatiramer acetate for five years. Upon treatment with steroids and an antihistamine along with discontinuation of glatiramer acetate, the urticaria resolved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer A. McCombe reports a relationship with Roche that includes: consulting or advisory. Jennifer A. McCombe reports a relationship with Novartis that includes: consulting or advisory., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Curative intent treatment of pancreatic adenocarcinoma (PDAC) relies on surgical resection. Modern treatment protocols focus on optimizing neoadjuvant therapy to increase resectability and improve oncologic outcomes. To elucidate differences in outcomes, we investigated the relationship between neoadjuvant chemotherapy (NAC), either with or without stereotactic body radiation therapy (SBRT), and vascular inflammation, surgical outcomes, and the resultant transcriptomic changes., Methods and Materials: Clinical data were collected from patients with borderline resectable PDAC (clinical T3-T4N0-1) who underwent NAC or NAC-SBRT followed by curative intent resection between 2014 and 2019. Vascular structures on surgical specimens were histologically evaluated for vasculitis. RNA sequencing was used to evaluate differential gene expression and to generate enrichment maps. Multivariate analysis was used to analyze the relationship between patient characteristics and oncological outcome., Results: In total, 46 patients met inclusion criteria (n = 12 NAC, n = 34 NAC-SBRT) with a median follow-up of 20.1 months. All patients underwent curative resection, with 91.3% achieving R0. There was no significant difference in patterns of failure, overall survival, or progression-free survival between NAC and NAC-SBRT groups. Patients with vasculitis had a lower median overall survival compared with those without (14.5 vs 28.3 months; hazard ratio, 12.96; 95% confidence interval, 3.55-47.28; P < .001). There was no significant correlation between inflammation and surgical complications or pathologic response. Neoadjuvant therapy did not have a significant effect on development of vasculitis (odds radio, 1.64 for NAC-SBRT; 95% confidence interval, 0.40-8.43; P = .52). Predictors of poor survival included perineural invasion and high baseline carbohydrate antigen 19-9 (CA19-9) (>191 U/mL). Patients with robust CA19-9 (>20% decrease) responses to neoadjuvant therapy had enrichment in immune response, chemotaxis, and cytotoxic T-cell and natural killer-cell proliferation., Conclusions: Vasculitis predicts for poor survival outcomes in patients with PDAC; NAC-SBRT did not increase the rate of vasculitis compared with NAC. Perineural invasion and CA19-9 remain strong prognosticators. Understanding and optimizing immune interactions remain a crucial hurdle in achieving response in pancreatic cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months, she presented respiratory infections, weight loss and enlarged cervical lymph nodes. On day two of admission, she displayed drowsiness and positive Romberg's sign; cerebrospinal fluid (CSF) workout revealed 107/ul cells, low glucose and high protein levels. Ceftriaxone and acyclovir were initiated, and she was transferred to our tertiary hospital. Brain magnetic resonance imaging showed punctiform focal areas of restricted diffusion in left capsular lenticular region suggestive of vasculitis secondary to infection. Tuberculin skin test and interferon-gamma release assay were positive. She started tuberculostatic therapy, but two days later she presented tonic-clonic seizures and impaired consciousness. Cerebral computed tomography (CT) revealed tetrahydrocephalus (Figure 1), needing external ventricular derivation. She had a slow clinical improvement, requiring several neurosurgical interventions and developing a syndrome of inappropriate antidiuretic secretion alternating with cerebral salt wasting. Positive results for Mycobacterium tuberculosis were obtained by CSF culture and by polymerase chain reaction in CSF, bronchoalveolar lavage and gastric aspirate specimens. Repeated brain CT showed a large-vessel vasculitis with basal meningeal enhancement, typical of central nervous system (CNS) tuberculosis (Figure 2). She completed one month of corticosteroids and maintained antituberculosis treatment. At two years of age, she has spastic paraparesis and no language skills. Portugal had 1836 cases of tuberculosis (17.8 per 100000) in 2016 and was considered a low-incidence country; consequently, BCG vaccination is not universal (1). We present a severe case of CNS tuberculosis with intracranial hypertension, vasculitis and hyponatremia, associated with poorer outcomes (2). A high index of suspicion allowed prompt start of antituberculosis treatment. Diagnosis was corroborated by microbiological positivity and a typical triad in neuroimaging (hydrocephalus, vasculitis and basal meningeal enhancement) (3), which we wish to emphasize.

Immunoglobulins that reversibly precipitate at temperatures below 37 °C are called cryoglobulins (CGs). Cryoglobulinemia often manifests as cryoglobulinemic vasculitis (CV), whose symptoms range in severity from purpuric eruptions to life-threatening features. The majority of CV patients are infected with hepatitis C virus (HCV), whereas lymphoproliferative disorders or connective tissue diseases (CTD) are commonly diagnosed among patients with CV of non-infectious origin. In the absence of detectable associated disease, cryoglobulinemia is classified as "essential" (EMC). All HCV-positive CV patients should be given direct-acting antiviral agents (DAAs) that are consistently able to induce a sustained virologic response (SVR). Glucocorticoids (GCs) can mitigate CV-associated vasculitis, but they have no role as maintenance therapy. Cyclophosphamide restrains the hyperactive phase(s) of the disease and the post-apheresis rebound of newly synthesized CGs. Its use has been largely replaced by rituximab (RTX) in patients unresponsive to DAAs, patients progressing to B-cell non-Hodgkin lymphoma (B-NHL) and patients in whom CV persists or reappears after clearance of HCV. Therapeutic apheresis is an emergency treatment for CV patients with hyperviscosity syndrome. HCV-positive CV patients are at an increased risk of developing NHL, but the achievement of SVR can effectively prevent HCV-related NHL or induce the remission of an already established lymphoma, even without chemotherapy. The treatment of patients with IgM or IgG monoclonal cryoglobulins and an underlying immunoproliferative disorder is based on the regimens adopted for patients with the same B-cell malignancies but without circulating CGs. For patients with CTD, GCs plus alkylating agents or RTX are similarly effective as first-line therapy and in the relapse/refractory setting. In patients with EMC, treatment should consist of GCs plus RTX, with the dose of GCs tapered as soon as possible to reduce the risk of infectious complications., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap., Methods: Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis., Results: Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1 , emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4 , RNF145 , IL12B , IL5 , IRF1 , IFNGR1 , PTK2B , TRIM35 , EGR2 and ETS2 , each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides., Conclusions: We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Immune check point inhibitors (ICIs) are a unique class of cancer treatments that harness the body's innate antitumor response. Although these medications have transformed oncology care, they also lead to generalized immune activation that can result in toxicities across a spectrum of organ systems called immune-related adverse events. This article reviews the most common rheumatologic immune-related adverse events and their management., Recent Findings: Inflammatory arthritis, polymyalgia rheumatic, sicca symptoms, systemic sclerosis, myositis, and vasculitis have all been reported as ICI adverse events. Treatment includes nonsteroidal anti-inflammatory drugs, glucocorticoids, traditional DMARDs, and biologics., Summary: Rheumatologists have an important role in the management of patients with rheumatologic immune-related adverse events. Working with our oncology colleagues, we can help manage rheumatologic immune-related adverse events while optimally preserving ICI's antitumor effects., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Objective: Hypertrophic pachymeningitis is a rare clinical disorder involving localized or diffuse thickening of the dura mater. Considering pachymeningitis is both in the clinical spectrum of IgG4-RD and ANCA vasculitis (specifically granulomatosis with polyangiitis), an overlap syndrome is discussed., Methods: We report a case of hypertrophic pachymeningitis revealed by headache and cranial nerve dysfunction, and coexistence of biopsy-proven IgG4-RD pachymeningitis and MPO-ANCA positivity. Furthermore, all cases previously reported in the literature of pachymeningitis with IgG4-RD and presence of ANCA were analyzed., Results: Thirteen patients with pachymeningitis, IgG4-RD and ANCA were analyzed. Patients with HP-related IgG4 and ANCA are mainly male (8, 62%). Median age at diagnosis was 64 years. Main clinical manifestations at diagnosis were localized to the head and neck with headaches (10, 77%), cranial nerve dysfunction (7, 54%), hearing impairment (6, 46%) and vertigo (4, 31%). Except 1 patient with diffuse aortitis, no other systemic manifestation was observed at diagnosis and during follow-up. Serum IgG4 was often elevated (11, 85%) and ANCA was mainly with myeloperoxidase specificity (11, 85%). Seven patients had cerebrospinal fluid analyse with lymphocytic pleocytosis in 5 cases (71%), elevated proteins in 4 cases (57%), positive oligoclonal bands in 3 cases (42%) and decreased glucose in one case (14%). On the MRI, the thickening of the dura mater concerned most often the posterior fossa, in 7 cases (54%). Among 10 cases with histological findings, all showed increased IgG4-positivity of plasma cells, 50% lymphocytic infiltrate but none presented the three major histological criteria of IgG4-related disease. Three (30%) showed histological signs of vasculitis with vascular wall damage and/or giant cells. Among the 12 patients treated with steroid therapy, a clinical improvement was noted in 11 cases (92%). Relapse occurred during tapering in 4 patients (33%). An immunosuppressive drug was added in 2nd line for 7 cases (54%), with a clinical improvement in all., Conclusion: Pachymeningitis with IgG4 and ANCA seems a localized disease to the head and neck. Leptomeningeal biopsy commonly found IgG4 criteria and no vasculitis. All patients responded well to steroid therapy and immunosuppressive drugs, especially rituximab, with clinical and radiological improvement but relapse and/or sequelae are not uncommon., Competing Interests: Declaration of Competing Interest There are no financial or other relationships that might lead to a conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)