Cutaneous vasculitis in autoinflammatory diseases.

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.

[Vasculitis as a cause of stroke]. / Vaskulity kak prichina insul'ta.

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).

Rare manifestations of cryoglobulinemic vasculitis: a case report.

Introduction: Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs. It is characterized by general symptoms, often accompanied by nonspecific cutaneous, articular, neurological, and renal manifestations. Diagnosing cryoglobulinemia through biological testing can be time-consuming and sometimes yields negative results, making diagnosis challenging. There are also other potentially life-threatening complications that can significantly impact prognosis and delay urgent treatment, including digestive manifestations and heart failure. Case presentation: We report the case of a 60-year-old male patient with a medical history of rheumatoid arthritis. He was admitted to the Nephrology Department for investigation of necrotic vascular purpura, acute kidney injury, and pancytopenia. Laboratory tests revealed consumption of the C3 and C4 complement fractions and the presence of mixed-type III cryoglobulinemia. Despite the initiation of the treatment, the patient rapidly developed multiple severe organ failures, including renal, cardiac, respiratory, and finally digestive complications. Acute colic ischemia led to emergency surgery and the patient was transferred to the Intensive Care Unit. Despite surgical intervention and hemodynamic support, the patient experienced multi-visceral organ failure and died two hours after admission. Discussion: Mixed cryoglobulinemia vasculitis may result in rare cases of acute and life-threatening organ damage, such as cardiac or respiratory failure with pulmonary hemorrhage, gastrointestinal ischemia, and neurological disorders. These severe manifestations are associated with a poor prognosis and it is crucial to promptly initiate an aggressive therapeutic strategy.

Limping as Presenting Symptom of Multisystem Inflammatory Syndrome in Children (MIS-C): a Case Report of Large Vessel Vasculitis in MIS-C.

Background: Multisystem Inflammatory Syndrome of children (MIS) is a pathological condition that occurs in response to a SARS-CoV-2 infection, the syndrome has been described as a "Kawasaki disease"-like illness and the spectrum of associated abnormalities, including vascular complications, remain to be fully defined. Objective: The aim of this article was to present a case of MISC presented with limping and associated with large vessel vasculitis. Case presentation: In this article we present a case of 10-year-old male presented to emergency department complaining of limping of one-week duration and left hip pain, associated with high grade prolonged fever, abdominal pain and weight loss. The patient was ill looking, couldn't bear weight and was admitted to pediatric intensive care unit. Laboratory workup have rule out infectious and malignant causes as well as known rheumatological causes. Inflammatory markers were elevated. Ultrasound, Doppler ultrasound, CT scan of the affected hip showed evidence of vasculitis extending from the left femoral artery reaching the left common iliac artery with intramural thrombus. According to WHO criteria the patient diagnoses was MIS-C. treatment was started immediately with IVIG and steroids in addition to anticoagulants, dramatic improvement was noticed within 24 hours. Patient was discharged after 10 days of hospitalization. Conclusion: MIS-C is a new emerging medical diagnosis after the pandemic of COVID-19. it is described a Kawasaki-like syndrome that affect small to medium vessels. This case reports a large vessel vasculitis associated with MIS-C, it helps the understand the extend of this new syndrome and the variety of complaints that may result from large vessels involvement.

Vasculitis associated with adenosine deaminase 2 deficiency: at the crossroads between Behçet's disease and autoinflammation. A viewpoint.

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.

Medium-vessel and large-vessel vasculitis in children.

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.

New-onset systemic vasculitis following SARS-CoV-2 infection and vaccination: the trigger, phenotype, and outcome.

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.

Ear, Nose, and Throat Manifestations of Vasculitis and Other Systemic Autoimmune Diseases: Otologic, Sinus, and Airway.

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.

Case Report: Interindividual variability and possible role of heterozygous variants in a family with deficiency of adenosine deaminase 2: are all heterozygous born equals?

Deficiency of adenosine deaminase 2 (DADA2) is a rare systemic autoinflammatory disease, typically with autosomal recessive inheritance, usually caused by biallelic loss of function mutations in the ADA2 gene. The phenotypic spectrum is broad, generally including fever, early-onset vasculitis, stroke, and hematologic dysfunction. Heterozygous carriers may show related signs and symptoms, usually milder and at an older age. Here we describe the case of two relatives, the proband and his mother, bearing an ADA2 homozygous pathogenic variant, and a heterozygous son. The proband was a 17-year-old boy with intermittent fever, lymphadenopathies, and mild hypogammaglobulinemia. He also had sporadic episodes of aphthosis, livedo reticularis and abdominal pain. Hypogammaglobulinemia was documented when he was 10 years old, and symptoms appeared in his late adolescence. The mother demonstrated mild hypogammaglobulinemia, chronic pericarditis since she was 30 years old and two transient episodes of diplopia without lacunar lesions on MRI. ADA2 (NM_001282225.2) sequencing identified both mother and son as homozygous for the c.1358A>G, p.(Tyr453Cys) variant. ADA2 activity in the proband and the mother was 80-fold lower than in the controls. Clinical features in both patients improved on anti-tumor necrosis factor therapy. An older son was found to be heterozygous for the same mutation post-mortem. He died at the age of 12 years due to a clinical picture of fever, lymphadenitis, skin rash and hypogammaglobulinemia evolving toward fatal multiorgan failure. Biopsies of skin, lymph nodes, and bone marrow excluded lymphomas and vasculitis. Despite being suspected of symptomatic carrier, the contribution of an additional variant in compound heterozygosity, or further genetic could not be ruled out, due to poor quality of DNA samples available. In conclusion, this familiar case demonstrated the wide range of phenotypic variability in DADA2. The search for ADA2 mutations and the assessment of ADA2 activity should be considered also in patients with the association of hypogammaglobulinemia and inflammatory conditions, also with late presentation and in absence of vasculitis. Furthermore, the clinical picture of the deceased carrier suggests a possible contribution of heterozygous pathogenic variants to inflammation.

[Diagnosis of cryoglobulinemic vasculitis based on B symptoms and peripheral neuropathy: a case report].

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 18F-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.

Vascular-Targeted Therapy for Systemic Lupus Erythematosus-Associated Vasculitis.

This case report describes a woman in her 40s with a medical history of systemic lupus erythematosus with 1 year of tender papules, plaques, and progressive ulcers on her hands and feet.

Another side of lupus: A case report of lupus presenting with cutaneous vasculitis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune complex disease that affects any organ, characterized by immune complex formation and autoantibody production. Lupus vasculitis begins at a young age. These patients generally have a longer disease duration. Ninety percent of cases in lupus-associated vasculitis present with cutaneous vasculitis. Disease activity, severity, organ involvement, response to treatment and drug toxicity determine the frequency of outpatient control in lupus. Depression and anxiety are observed more frequently in SLE than in the normal population. Our case, it is an example of the patient's disruption of controls due to psychological trauma and that lupus can cause serious cutaneous vasculitis. In addition, psychiatric evaluation of lupus cases from the time of diagnosis may have a positive effect on the prognosis.

Vasculitis, CA19-9, and Perineural Invasion Differentially Predict Response and Surgical Outcome in Pancreatic Ductal Adenocarcinoma.

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.