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Purpose of Review: This review will provide updates in the outcomes in the common rheumatologic diseases with kidney involvement. Covered are also advances in therapeutics for the use of pediatric rheumatologic diseases with kidney involvement, as well as the potential kidney complications from other rheumatologic diseases and their medications., Recent Findings: Two of the more common rheumatologic diseases with kidney involvement, lupus and vasculitis, continue to show inadequate response to initial therapy of renal disease and practice continues to be driven by results of adult studies., Summary: There is a continued need for pediatric specific studies in rheumatologic diseases with kidney involvement as outcomes continue to be inadequate. Despite recently approved treatments for adults with rheumatic diseases and kidney involvement, therapeutic options in pediatrics remain limited, contributing to the overall morbidity and mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Vaccinations are essential in minimizing the effects of global health crises including COVID-19 pandemic. This study investigates the potential association between COVID-19 vaccination and the occurrence of medium vessel vasculitis., Methods: Several databases were utilized to conduct a comprehensive literature review. The studies were carefully evaluated to ensure their quality and eliminate any potential bias., Results: After reviewing 935 search results and removing duplicates, we selected 10 case reports. We discovered that medium vessel vasculitis may occur after COVID-19 vaccination, typically appearing around 16.2 days after vaccination. The patients in the study had a median age of 43.5 years and were predominantly males (80%). Additionally, half of the cases were reported after the second dose of vaccination., Conclusions: Vaccination-associated vasculitis is a rare yet possible complication of COVID-19 vaccination and lacks a clear treatment protocol., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Infective endocarditis is a rare but life-threatening condition, occasionally linked to diverse immunologic manifestations, including mixed cryoglobulinemia. This can lead to cryoglobulinemic vasculitis, which has the potential for widespread organ damage. Although some cases have highlighted the relationship between infective endocarditis and cryoglobulinemic vasculitis, no comprehensive epidemiological evaluation or optimal treatment strategies have been advanced for such a combination. We present a case of methicillin-sensitive Staphylococcus aureus infective endocarditis associated with cryoglobulinemic vasculitis and conduct a literature review to compare management and outcomes in similar cases. Our patient presented with classical Meltzer's triad and mild renal involvement. Cryoimmunofixation confirmed type III cryoglobulinemia, and serum cytokines showed elevated IL-6 levels. The differential diagnosis included infective endocarditis and chronic active hepatitis C virus infection. Rapid symptom resolution after antibiotic treatment identified infective endocarditis as the likely cause of cryoglobulinemic vasculitis. Our case and review of the literature highlight that early identification of the cause of cryoglobulinemic vasculitis is crucial for selecting appropriate treatment and preventing recurrence or morbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Reinberg, Vingerhoets, Pavlova, Guenova, Papadimitriou-Olivgeris and Comte.)

Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCV pos MCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCV pos MCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCV pos MCV. The prevalence of HBsAg seroclearance was 48% within 123 HCV pos MCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCV pos MCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCV pos MCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCV pos MCV in male CHC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Morrone, Fiorilli, Cinti, Roberto, Ferri, Visentini, Pulsoni, Spinelli, De Santis, Antonelli, Basili, Tosti, Conti and Casato.)

Skin lesions are frequently observed in children with rheumatic diseases, particularly in conditions such as IgA vasculitis (IgAV) and Kawasaki disease (KD). In paediatric vasculitis, the presence of skin lesions serves as an early indicator, emphasising the importance of timely diagnosis to prevent complications, such as cardiac or renal involvement. Conversely, autoinflammatory disorders like juvenile systemic lupus erythematosus (SLE) and juvenile dermatomyositis (DM) may manifest with cutaneous manifestations either at the onset of disease or during its progression. Identifying these skin lesions prior to the appearance of systemic symptoms offers an opportunity for early diagnosis and treatment, which has a positive influence on the outcomes. Additionally, it is noteworthy that specific rheumatological conditions, such as acute rheumatic fever (ARF) or oligoarticular or polyarticular forms of juvenile idiopathic arthritis (JIA), may exhibit occasional, but significant skin involvement, which is strongly correlated with an unfavourable prognosis. The assessment of skin is important in the holist approach to assessing patients for potentially systemic/multisystem disorder and helps distinguish discrete conditions.

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: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD., Methods: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram., Results: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages., Conclusion: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lombardi Pereira, Aubuchon, Moreira, Lane, Carvalho, Mesquita, Lee, Crother, Porritt, Verri, Noval Rivas and Arditi.)

Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava. This demonstrates that the proteinuria was caused by increased intraglomerular pressure due to venous outflow obstruction as a consequence of venous vasculitis. To our knowledge, this is the first report of massive proteinuria caused by venous obstruction of the caval vein in the context of BD. Altogether, this case demonstrates the extensive spectrum of vascular disease in BD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cryoglobulinaemia vasculitis can present with a variety of symptoms and there is limited data on the incidence and presentation of cryoglobulinaemia vasculitis in haemodialysis patients. We report a case of a 63-year-old male who had a series of presentations with rash, visual changes, abdominal pain, weight loss, fevers and digital ischaemia. This is on a background of a congenital single kidney with end-stage renal failure secondary to diabetes and hypertension, receiving haemodialysis for nearly 5 years. He initially experienced a leukocytoclastic vasculitis rash confirmed on skin biopsy, followed by multiple hospital presentations for undifferentiated abdominal pain and fever of unknown source. Jejunal biopsy revealed intestinal vasculitis. His peripheral blood flow cytometry and bone marrow biopsy were consistent with marginal zone lymphoma (indolent subtype, IgM kappa clone). Further testing revealed a type II cryoglobulinaemia consisting of an IgM kappa monoclonal band with polyclonal IgG (cryocrit 5%). A diagnosis of cryoglobulinaemia vasculitis was established and he was treated with pulsed methylprednisolone and rituximab therapy. However, after receiving three doses of rituximab the patient developed a presumed vasculitis-associated pulmonary haemorrhage for which he received treatment with five sessions of plasma exchange. His symptoms resolved and cryocrit reduced to < 1% after his final dose of rituximab. The clinical features of cryoglobulinaemia may be difficult to detect in chronic haemodialysis patients and vigilance is required., (© 2023. Crown.)

Scurvy is a nutritional disease caused by ascorbic acid (vitamin C) deficiency. Althought currently it is a rare disease, we should considerer it in the differential diagnosis of purpura and arthritis in patients with restrictive diets. We present the case of a 49-year-old man with a history of a nutritional disorder presented to our hospital with generalized purpura and hemarthros. Following the anamnesis and laboratory findings, rheumatological, infectious and hematological etiologies were excluded. Finally, the diagnosis of scurvy was made upon demostration poor levels of vitamin C and a spectacular response to nutritional supplements. We compare this case with 19 similar cases reported in the medical literature., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Antiphospholipid antibodies (aPL) are both laboratory evidence and causative factors for a broad spectrum of clinical manifestations of antiphospholipid syndrome (APS), with thrombotic and obstetric events being the most prevalent. Despite the aPL-triggered vasculopathy nature of APS, vasculitic-like manifestations rarely exist in APS and mainly appear associated with other concurrent connective tissue diseases like systemic lupus erythematous. Several studies have characterized pulmonary capillaritis related to pathogenic aPL, suggesting vasculitis as a potential associated non-thrombotic manifestation. Here, we describe a 15-year-old girl who develops hepatic infarction in the presence of highly positive aPL, temporally related to prior non-severe COVID-19 infection. aPL-related hepatic vasculitis, which has not been reported before, contributes to liver ischemic necrosis. Immunosuppression therapy brings about favorable outcomes. Our case together with retrieved literature provides supportive evidence for aPL-related vasculitis, extending the spectrum of vascular changes raised by pathogenic aPL. Differentiation between thrombotic and vasculitic forms of vascular lesions is essential for appropriate therapeutic decision to include additional immunosuppression therapy. We also perform a systematic review to characterize the prevalence and clinical features of new-onset APS and APS relapses after COVID-19 for the first time, indicating the pathogenicity of aPL in a subset of COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Zhou, Ge, Liu, Li and Zhang.)

The mechanisms underlying the onset and progression of vasculitis remain poorly understood. This condition is characterized by damage to the vascular wall, recruitment of inflammatory cells, and subsequent structural remodeling, which are hallmarks of vasculitis. The histopathological classification of vasculitis relies on the size of the affected vessel and the predominant type of inflammatory cell involved - neutrophils in acute cases, lymphocytes in chronic conditions, and histiocytes in granulomatous forms. Pathological changes progress in every context, and a single vasculitic pattern can be associated with various systemic conditions. Conversely, a single causative agent may lead to multiple distinct clinical and pathological manifestations of vasculitis. Moreover, many cases of vasculitis have no identifiable cause. A foundational understanding of the normal structure of the cutaneous vascular network is crucial. Similarly, identifying the cellular and molecular participants and their roles in forming the "dermal microvascular unit" is propedeutical., This review aims to elucidate the complex mechanisms involved in the initiation and progression of vasculitis, offering a comprehensive overview of its histopathological classification, underlying causes, and the significant role of the cutaneous vascular network and cellular dynamics. By integrating the latest insights from studies on NETosis and the implications of lymphocytic infiltration in autoimmune diseases, we seek to bridge gaps in current knowledge and highlight areas for future research. Our discussion extends to the clinical implications of vasculitis, emphasizing the importance of identifying etiological agents and understanding the diverse histopathological manifestations to improve diagnostic accuracy and treatment outcomes., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult-onset VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small-vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis-like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle-aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life-threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome-like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes., (© 2023 Japanese Dermatological Association.)

Competing Interests: Competing interests: None declared.

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.)

The global health crisis caused by the COVID-19 pandemic overwhelmed the capacity of healthcare systems to cope with the rapidly spreading infection and its associated complications. Among these complications, autoimmune phenomena such as systemic vasculitis emerged as a significant challenge. Both the SARS-CoV-2 virus and the vaccines developed to combat it appeared to induce clinical manifestations resembling various types of systemic vasculitis, affecting large, medium, and small vessels. These virus- or vaccine-induced vasculitides exhibited a distinct natural history and course from de novo vasculitis, as they were more responsive to steroid therapy and some mild cases even resolved spontaneously. Notably, there have been no confirmed cases of SARS-CoV-2 infection or vaccination triggering variable vessel vasculitis like Behcet's disease or Kawasaki disease. IgA vasculitis, which is predominantly a pediatric condition, was more prevalent in adults after COVID-19 infection and they had a favorable outcome with glucocorticoid treatment. The impact of immunosuppression, especially B-cell-depleting agents, on the immunogenicity of the vaccine was evident, but there was no significant increase in the incidence of SARS-CoV-2 infection in these patients compared to the general population. Considering their relatively benign course, these post-COVID or post-vaccine vasculitides seem to be amenable to 0.8 to 1 mg/kg prednisolone or equivalent, which could be gradually tapered. The need for immunosuppression and the duration of steroid therapy should be determined on an individual basis. While the world still reels from the perils of a deadly pandemic, the aftermath continues to haunt. Our narrative review aims to explore the effects of COVID and the vaccine on systemic vasculitis, as well as the effect of disease and immunosuppression on the immunogenicity of the COVID vaccine., (© 2023. International League of Associations for Rheumatology (ILAR).)

Adenosine deaminase 2 deficiency (DADA2) is a rare monogenic vasculopathy caused by loss-of-function homozygous or compound heterozygous mutations in ADA2, formerly CECR1 (cat eye syndrome chromosome region 1) gene. The DADA2 phenotype is widely heterogeneous, and patients may present with fever, weight loss, livedo reticularis/racemosa, digital ischemia, cutaneous ulceration, peripheral neuropathy, abdominal pain, bowel perforation, and portal or nephrogenic hypertension. More specific manifestations include early-onset ischemic or hemorrhagic stroke, mild immunodeficiency and hypogammaglobinemia, cytopenia, and vision disturbances. Herein, we present the case of a young male with vasculitis associated with DADA2. The presence of HLA-B51 and the clinical features of this patient raised the question of similarities between ADA2 deficiency, Behçet's disease, and NOD2-associated diseases. Treatment of this rare monogenic disease is challenging and based on small case series. The long-term experience of this patient proved the difficulties of prednisone tapering and the lack of satisfactory therapeutic strategies.

Purpose of Review: This article serves as an up-to-date examination of the latest findings in the field of paediatric large-vessel and medium-vessel vasculitis., Recent Findings: Over the last 2 years and in the wake of SARS-CoV2 pandemic, a multitude of studies have increased our insight into these conditions. Although large-vessel and medium-vessel vasculitis are uncommon amongst children, they are a complex and multisystem with a constantly evolving landscape. Increasing numbers of reports from low-income and middle-income countries are shaping our understanding of the epidemiology of vasculitis in children. The influence of infectious disease and the microbiome are of particular interest in unravelling pathogenetic aspects. Improved understanding of the genetics and immunology offer opportunities for better diagnostic options and biomarkers of disease as well as targeted therapies., Summary: In this review, we address recent findings in epidemiology, pathophysiology, clinical findings, bio-markers, imaging and treatment that have the potential to offer better management solutions for these uncommon conditions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Auricular, nasal, and laryngeal manifestations occur frequently in rheumatic diseases. Inflammatory ear, nose, and throat (ENT) processes often result in organ damage and have profound effects on quality of life. Herein, we review the otologic, nasal, and laryngeal involvement of rheumatic diseases, focusing on their clinical presentation and diagnosis. ENT manifestations generally respond to treatment of the systemic disease, which is outside the scope of this review; however, adjunctive topical and surgical treatment approaches, as well as treatment of idiopathic inflammatory ENT manifestations will be reviewed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A 72-year-old woman had a history of chronic hepatitis C virus (HCV) infection previously treated with interferon to achieve a sustained virologic response. Thereafter, she developed polyarthritis and purpura of the lower extremities as well as progressive renal dysfunction with hypertension and proteinuria that had occurred in the last three months. Laboratory investigations revealed seropositivity for cryoglobulin but negative findings for HCV RNA. She was ultimately diagnosed with cryoglobulinemic glomerulonephritis complicated by monoclonal gammopathy of undetermined significance (MGUS) based on the pathological findings of the kidney and bone marrow, indicating that MGUS-induced cryoglobulinemic vasculitis may occur even after HCV elimination.

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 man in his 50s presented with a 2-month history of paresthesia and hypoesthesia of the extremities and B symptoms including low-grade fever, weight loss, and night sweats. He also reported a 3-year history of skin discoloration in cold weather. Laboratory test results showed a high white blood cell count and elevated serum C-reactive protein and rheumatoid factor (RF) levels. Complement levels were low, and tests for cryoglobulin showed positive results. Computed tomography revealed generalized lymphadenopathy, and 18 F-fluorodeoxyglucose-positron emission tomography showed increased uptake; therefore, we performed cervical lymph node and muscle biopsies. The patient was diagnosed with nodular marginal zone lymphoma and cryoglobulinemic vasculitis (CV) and received chemotherapy and steroid treatment with improvement in symptoms. CV is a rare immune complex small-vessel vasculitis. It is important to measure RF and complement levels and consider infections, collagen diseases, and hematological disorders in the differential diagnosis in patients with suspected vasculitis or CV.

Competing Interests: Declaration of competing interest The authors have no competing interests to declare.

Cryoglobulinemia is a rare entity which frequently occurs in the setting of an underlying disease, with chronic hepatitis C virus infections and primary Sjogren syndrome being the most common underlying conditions. Cryoglobulinemic vasculitis (CV) is an immune-mediated type of small-vessel vasculitis with a broad spectrum of specific organ involvement, including renal, pulmonary, peripheral nerve, and cutaneous involvement and variable manifestations that can be life threatening. Moreover, a strong relationship between cryoglobulinemia and CV, with the future development of lymphoma, is well established. We present the case of a 72-year-old Caucasian male referred for nephrotic syndrome and acute renal injury. A diagnosis of Sjogren syndrome-associated CV was made, and he was successfully treated with rituximab and plasma exchange sessions., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Kidney Diseases and Transplantation.)

Competing Interests: M. Samson déclare des interventions ponctuelles pour Roche Chugai, Novartis, Vifor Pharma, AbbVie, Argenx, GSK et avoir été pris en charge à l’occasion de déplacement pour congrès par Roche Chugai, AbbVie, Novartis, Vifor Pharma, GSK. H. Greigert déclare n’avoir aucun lien d’intérêts. B. Bonotte déclare des interventions ponctuelles pour Roche Chugai, Amgen, Novartis, LFB, Boehringer Ingelheim, Eusa Pharma et avoir été pris en charge à l’occasion de déplacement pour congrès par Novartis, Otsuka, AstraZeneca.

Objective: COVID-19-associated pediatric vasculitis, other than Kawasaki disease (KD)-like vasculitis in multisystem inflammatory syndrome in children (MIS-C), is very rare. This study sought to analyze the characteristics, treatment, and outcomes in patients with COVID-19-associated pediatric vasculitis (excluding KD-like vasculitis in MIS-C)., Methods: The inclusion criteria were as follows: 1) age <18 years at vasculitis onset; 2) evidence of vasculitis; 3) evidence of SARS-CoV-2 exposure; and 4) ≤3 months between SARS-CoV-2 exposure and vasculitis onset. Patients with MIS-C were excluded. The features of the subset of patients in our cohort who had COVID-19-associated pediatric IgA vasculitis/Henoch Schönlein purpura (IgAV/HSP) were compared against a pre-pandemic cohort of pediatric IgAV/HSP patients., Results: Forty-one patients (median age 8.3 years; male to female ratio 1.3) were included from 14 centers and 6 countries. The most frequent vasculitis subtype was IgAV/HSP (n = 30). The median duration between SARS-CoV-2 exposure and vasculitis onset was 13 days. Involvement of the skin (92.7%) and of the gastrointestinal system (61%) were the most common manifestations of vasculitis. Most patients (68.3%) received glucocorticoids, and 14.6% also received additional immunosuppressive drugs. Remission was achieved in all patients. All of the patients with IgAV/HSP in our cohort had skin manifestations, while 18 (60%) had gastrointestinal involvement and 13 (43.3%) had renal involvement. When we compared the features of this subset of 30 patients to those of a pre-pandemic pediatric IgAV/HSP cohort (n = 159), the clinical characteristics of fever and renal involvement were more common in our COVID-19-associated pediatric IgAV/HSP cohort (fever, 30% versus 5%, respectively [P < 0.001]; renal involvement, 43.3% versus 17.6%, respectively [P = 0.002]). Recovery without treatment and complete recovery were each less frequent among our COVID-19-associated pediatric IgAV/HSP patients compared to the pre-pandemic pediatric IgAV/HSP cohort (recovery without treatment, 10% versus 39%, respectively [P = 0.002]; complete recovery, 86.7% versus 99.4%, respectively [P = 0.002])., Conclusion: This is the largest cohort of children with COVID-19-associated vasculitis (excluding MIS-C) studied to date. Our findings suggest that children with COVID-19-associated IgAV/HSP experience a more severe disease course compared to pediatric IgAV/HSP patients before the pandemic., (© 2022 American College of Rheumatology.)

Urticarial vasculitis (UV) is a rare entity characterised by long-lasting recurrent episodes of urticarial lesions. Although frequently idiopathic, UV has been associated with multiple diseases, including infections. We present a case of Lyme disease (LD) as a trigger of normocomplementemic UV, a very rarely described association. The patient presented first with episodes of inflammatory polyarthritis and a positive serology for Borrelia burgdorferi , later followed by the appearance of long-lasting urticarial lesions, histologically suggestive of UV. Lyme arthritis resolved with doxycycline, but UV persisted. Response to cyclosporine was satisfactory but with side effects, and only methotrexate showed substantial and consistent improvement. This case reminds physicians that chronic urticaria with atypical characteristics should raise suspicion of UV. Possible triggers for this disease must be sought, even if rarely described, such as LD. Normocomplementemic UV frequently presents a therapeutic challenge, but methotrexate can be a particularly effective therapy in this setting.

Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5 years (4-26 years). The clinical presentation was before the age of 5 months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Exacerbations or de novo autoimmune/autoinflammatory disease have been reported after COVID-19 vaccination. A young male presented with cutaneous IgA vasculitis with glomerular hematuria, diarrhea and pericarditis following his second COVID-19 mRNA vaccination. He also showed positivity for proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) and anti-cardiolipin antibody. Skin biopsy was compatible to IgA vasculitis. His purpura subsided and hematuria spontaneously disappeared. Treatment with anti-inflammatory medications and prednisolone resolved the pericarditis. He had a history of persistent diarrhea, and colonic biopsies showed possible ulcerative colitis without vasculitis. Kidney biopsy after prednisolone therapy revealed minor glomerular abnormalities without any immune reactants and did not show vasculitis. After prednisolone treatment, PR3-ANCA decreased in a medium degree despite of improvement of symptoms and inflammatory data, suggesting that his PR3-ANCA may be associated with ulcerative colitis. The cause of the transient glomerular hematuria was unclear, however, it might be caused by focal glomerular active lesions (glomerular vasculitis) due to vaccine-induced IgA vasculitis with nephritis. This case highlights that COVID-19 mRNA vaccination can activate multiple autoimmune/autoinflammatory systems. The conditions might help us better understand the mutual mechanisms of the relevant disorders., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

The review considers the clinical picture, key aspects of the diagnosis and treatment of vasculitis that are the causes of strokes (giant cell arteritis, polyarteritis nodosa, varicella zoster virus vasculopathy, cerebrovascular pathology caused by herpes simplex virus types 1 and 2, primary CNS angiitis, adenosine deaminase-2 deficiency).

Background: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF's target molecules., Methods: Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (-) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day., Results: The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group., Conclusions: The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg., (© 2022. The Author(s).)

Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE-) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD., Competing Interests: The authors declare no conflict of interest.

Cryoglobulins are immunoglobulins that precipitate in vitro when serum is incubated at temperatures lower than 37°C. Cryoglobulins are classified under three subgroups according to their components. Cryoglobulinemic vasculitis corresponds to manifestations associated with vascular occlusion by cryoglobulins or inflammatory manifestations induced by the deposition of cryoglobulins containing immune complex. Main manifestations are skin lesions, including vascular purpura, necrosis, kidney involvement, and peripheral nerve involvement. Initial work-up aims at identifying the underlying disease, which may be a B-lineage hematological malignancy, a connective tissue disorder, or a chronic viral infection like hepatitis C. Treatment and prognosis are closely dependent of the underlying disease., Competing Interests: A. Mirouse déclare n’avoir aucun lien d’intérêts. D. Saadoun déclare des interventions ponctuelles pour Sanofi et GSK. P. Cacoub déclare n’avoir aucun lien d’intérêts.