Manifestations Of Vasculitis Research Articles

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.

P19 Our experience diagnosing and treating deficiency of adenine deaminase 2 (DADA2) vasculitis

Abstract Introduction Deficiency of adenine deaminase 2 (DADA2) is caused by biallelic pathogenic variants in the gene on chromosome 22q11. It is autosomal recessive with incomplete penetrance, and a variable presentation. It typically manifests as a systemic vasculopathy with early onset strokes, cutaneous manifestations, immunodeficiency and cytopenia. Traditional immunosuppressants have limited efficacy, but vasculitic manifestations have been reported to respond to biologic TNF-inhibitors. We report a patient with confirmed ADA2 deficiency whose cutaneous manifestations were previously classified as Sneddon syndrome. After a period of stability on adalimumab she developed marked cutaneous ulceration that healed following a therapy switch to intravenous infliximab. Case description We report a 39-year-old female with a long clinical history that started in childhood when she developed Diamond-Blackfan anaemia that went into remission following corticosteroid treatment and transfusions. In 2006, she suddenly had two thalamic infarcts and was thoroughly investigated but was found to have unremarkable vascular imaging, a negative antiphospholipid syndrome and autoantibody testing, a modestly elevated CRP (5-15 mg/L) and a notably persistent low serum IgM. She continued to experience frequent migraines associated with transient sensorimotor symptoms. Subsequently, she developed recurrent botchy, polymorphic macular eruptions on the lower limbs. A deep cutaneous biopsy demonstrated lymphocytic predominant perivascular inflammation of deep dermal vessels associated with thrombus formation and endothelial proliferation. A putative diagnosis of Sneddon’s syndrome was made. However, after the subsequent identification of ADA2-deficiency vasculitis, the patient underwent genetic screening which identified a compound heterozygosity for two novel ADA2 mutations (c6634_636, delTTC (p.Phe212del) and c.1225C>T (p.Pro409Ser)). Her mother was as a carrier. She was started on adalimumab injections to which she had a good clinical response with improved cutaneous disease and no further neurological symptoms. However, after two years of disease stability, she then developed a significant ‘punched out’ ulcer on the mid-calf which was painful and increasing in size to a maximum of 2 x 3 cm. Dermatology colleagues were reluctant to re-biopsy due to a high likelihood of non-specific appearances and increased risk of poor healing leading to worsening ulceration. Drawing on experience from rheumatoid arthritis that a switch in anti-TNF biological will often restore efficacy following secondary non-response to adalimumab; we empirically switched treatment to intravenous infliximab, with a reducing course of prednisolone (40mg per day tapering to 5mg after 12 weeks). This was associated with a notable improvement within one month and a complete healing of the ulcer within 4 months. Discussion DADA2 remains a rare condition with a carrier frequency estimated at 1 in 236 persons worldwide and a predicted disease prevalence of approximately 1 in 222,000 persons. Patients with DADA2 who have haematological manifestations tend to present during early infancy, whereas delayed presentation is common in patients with vasculitis and systemic inflammation. It should be suspected in patients with early onset strokes, livedo and other haematological and immunological features. Additionally, many previously diagnosed cases of Sneddon syndrome may in fact have DADA2, with a low IgM level favouring the later. Diagnosis can be confirmed by genetic studies or by a biochemical assay that demonstrates near-absent levels of ADA2 activity in the plasma or serum. Interestingly, on screening of adult patients with polyarteritis nodosa (PAN) 3.4% possessed biallelic pathogenic ADA2 variants and similarly, in genomic survey of patients with Diamond-Blackfan anaemia 2% possessed biallelic pathogenic ADA2 variants in the absence of the ribosomal protein gene mutations associated with it. Treatment is phenotype based with a preference for lifelong TNF inhibitor and biosimilar use in those with vasculitis and/or systemic inflammation, though not currently commissioned for this indication. Glucocorticoids, disease-modifying antirheumatic drugs, and other biologic agents may partially ameliorate systemic inflammation. Unfortunately, they are all ineffective for severe hematologic manifestations and hematopoietic cell transplantation (HCT) is currently the only treatment option. Treating asymptomatic patients and mildly symptomatic patients picked up on screening remains senior clinician led on a risk benefit basis. Disease activity is clinically monitored with an overall mortality rate estimated at 8%. Key learning points The main learning points for me included an increased awareness of this syndrome, its variable presentation, association with other autoimmune illnesses, diagnosis, and treatment initiation. In addition, I learnt about screening of family members, weighing the benefits versus risks when considering treating mildly symptomatic and asymptomatic patients, clinical monitoring for response, and when to switch to other anti-TNFs and biosimilars. From this conference, I would like to explore the experience of our rheumatology colleagues with similar cases.

Clinicopathological characteristics and key therapeutic options for liver involvement with vasculitis

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.

Monogenic autoinflammatory syndromes with features of systemic vasculitis: a new field of rheumatology

The article is dedicated to a new actual problem in rheumatology: vasculitis and vasculitis-like manifestations in monogenic autoinflammatory syndromes in adult. The features of the clinical course of the rarely diagnosed VEXAS syndrome, as well as the SAVI and COPA syndromes, which sometimes occur in adults, are considered. Promising directions of future treatment are discussed.

#5627 SYSTEMATIC HISTOLOGICAL SCORING OF TUBULOINTERSTITIAL LESIONS CORRELATE WITH CLINICAL PARAMETERS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Small vessels in the kidney include small-sized arteries (interlobular artery, afferent and efferent arteriole), capillaries (glomerular and peritubular capillary) and venules. Although crescentic ANCA glomerulonephritis (GN) is a common histological finding reflecting glomerular small vessel vasculitis, it is reasonable that manifestation of AAV could also contribute to interstitial small vessel vasculitis. Therefore, we here aimed to expand our current knowledge focusing on interstitial vasculitis in ANCA GN by systematic histological scoring of vascular lesions analogous to Banff. Method A total number of 49 kidney biopsies with confirmed renal involvement of AAV at the University Medical Center Göttingen were retrospectively included between 2015 till 2020. A renal pathologist evaluated all biopsies and was blinded to clinical data collection and analysis. A detailed methological section is provided in the Supplementary material and methods section. Results Since previous studies established that crescentic ANCA GN associates with severe kidney injury and acute deterioration of kidney function in AAV, we first systematically scored interstitial vasculitis in association with requirement of renal replacement therapy (RRT). Among all active and chronic tubulointerstitial lesions analogous to the Banff scoring system, the only association between severe kidney injury requiring RRT was observed for interstitial vasculitis in AAV reflected by peritubular capillaritis (ptc, p = 0.0002) and arteritis (v, p = 0.0069), affecting 5/49 (10.2%) and 11/49 (22.4%) of renal biopsies, respectively. Since it is known that severe deterioration of kidney function also correlates with crescentic ANCA GN, we next directly compared glomerular and tubulointerstitial lesions. The fraction of normal glomeruli was inversely associated with interstitial fibrosis (ci), total (ti) and inflammation in IFTA (i-IFTA), whereas glomerular crescents were associated with interstitial inflammation (i), tubulitis (t) and total inflammation (ti). In contrast, global glomerular sclerosis associated with less interstitial inflammation (i) but correlated with interstitial fibrosis (ci) and tubular atrophy (ct), confirming established mechansim that chronic glomerular injury leads to tubular atrophy and interstitial fibrosis. Interestingly, no association between interstitial vasculitis (ptc and v correlating with severe kidney injury) and any glomerular lesion in ANCA GN (also correlating with severe kidney injury) was observed, thereby confirming that interstitial vasculitis contributes to severe kidney injury independent of ANCA GN. By contrast, short-term renal recovery from RRT was equal in both groups, suggesting a distinct association with acute decline of kidney function at disease onset. Conclusion Taken together, by using the Banff scoring system we here expand our current knowledge of renal interstitial lesions in AAV revealing peritubular capillaritis and arteritis as important histological alterations associated with severe kidney injury in a considerable subset of AAV. Furthermore, our findings that interstitial vasculitis did not correlate with crescentic ANCA GN implicate that the characteristics of each vasculitis manifestation are independent and could further improve our understanding of mechanisms contributing to renal injury. These observations suggest that interstitial vasculitis in AAV may also affect long-term prognosis requiring further investigation.

New therapeutic approaches with biological drugs for eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multiorganic syndrome that affects the cardiovascular, neurologic, renal, and gastrointestinal systems with an incidence ranging from 0 case to 67 cases per one million person-years, and its pathophysiology remains unknown. It is believed that genetic factors, the environment, and changes in immune system function contribute to the development of EGPA, overlapping the immune mechanisms of vasculitides and the pathologic mechanisms in eosinophilic syndromes. This disease is commonly divided into two phenotypes depending on the presence of antineutrophil cytoplasmic antibodies (ANCA). ANCA-positive patients usually have more vasculitic manifestations like peripheral neuropathy, purpura, renal involvement, and biopsy-proven vasculitis. The keystone of EGPA therapy is systemic corticosteroids (CS) as monotherapy or in combination with other immunosuppressive treatments, and recently the efficacy of eosinophil-targeted biotherapy, anti-interleukin-5 (IL-5), has been shown to be efficacious in EGPA. Although this phenotype/phase distinction has not yet had an impact on the current treatment strategies, emerging targeted biotherapies under evaluation could lead to a phenotype-based approach and personalised treatment regimens for EGPA patients. The present review describes the new therapeutical approaches with biological drugs for EGPA.

Assessment of Cutaneous Vasculitis and Quality of Life

This survey study assesses the health-related quality of life outcomes in adult patients with cutaneous manifestations of vasculitis.

CHARACTERISTICS OF THE COURSE OF LEUCOCYTOCLASTIC VASCULITIS WITH SKIN LESIONS. ANALYSIS OF CLINICAL CASES

The article describes the features of the course of leukocytoclastic skin vasculitis with consideration of 3 clinical cases. Leukocytoclastic vasculitis of the skin (LCV) is an isolated cutaneous vasculitis without damage to internal organs. At present, vasculitis is considered a polyetiological disease. The most frequent causes of the development of vasculitis limited to the skin include various acute or chronic infections: bacterial, viral, and fungal. It can be caused by medications, and sometimes the cause cannot be found. When LVC is suspected, an extensive examination is usually required to determine whether the process is limited to the skin or is a manifestation of systemic vasculitis or other systemic diseases. Diagnosis and treatment of LCV is a complex problem in the practice of doctors of many specialties, such as rheumatologists, dermatologists, and therapists, family doctors, which requires close cooperation of specialists. We present 3 clinical cases of patients who were hospitalized in the clinic with symptoms of skin lesions and suspicion of LCV after taking medications. The paper describes various skin manifestations and the results of the examination and treatment. The differential diagnostics enabled us to diagnose LCV in 2 cases, in one case – generalized urticaria due to taking furazolidone. It should be noted that drug reactions with skin lesions constitute a serious medical problem, whose relevance is increasing every year. This is largely due to widespread uncontrolled drug intake among the population, and frequent polypharmacy during treatment under the supervision of medical professionals. Multidisciplinary problems, which are solved by doctors of various specialties at different stages and levels of medical care, including drug-induced skin lesions in patients, are particularly difficult. Strengthening medical control over the prescription and administration of medicinal products, and improving the awareness of doctors of all specialties regarding the diagnosis and treatment of medicinal reactions is the way to solve the problem.

Neurosyphilis Presenting as Limbic Encephalitis: a Case Report (P10-10.007)

<h3>Objective:</h3> To present an interesting case of neurosyphilis mimicking limbic encephalitis. <h3>Background:</h3> Neurosyphilis can occur at any stage of infection and it classically presents as meningitis, cranial neuropathies, vasculitis, tabes dorsalis, or neuropsychiatric manifestations, however rarely temporal lobe abnormalities resembling limbic encephalitis have been reported. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 51-year-old male with no past medical history presents initially with 3 weeks of altered mental status, confusion and memory loss. Prior to admission to the hospital, he presented with a generalized tonic-clonic seizure. His MRI showed T2 hyperintensities in the left hippocampus, amygdala, and mesial temporal lobe with associated diffusion restriction. Cerebrospinal fluid (CSF) studies showed 58 white blood cells/mm3 (73% lymphocytes), a protein concentration of 165 mg/dL and a glucose concentration of 35 mg/dL. HIV serology, serum cryptococcal Antigen, HSV and VZV PCR on CSF and neuronal autoantibodies on serum were negative. EEG showed left lateralized periodic discharges. The patient was initially treated with empiric anti-infective therapy including acyclovir, ceftriaxone, and ampicillin. Subsequently, serum syphilis screen was positive with reflex Rapid Plasma Reagin (RPR) titer at 1:64. CSF Venereal Disease Research Laboratory (VDRL) was positive at 1:64. In light of these results, the patient was transitioned to intravenous aqueous penicillin G 24 million units daily through continuous infusion. His mental status markedly improved after a few days of treatment. Repeat EEG showed only mild encephalopathy. He was discharged on levetiracetam and high dose IV penicillin G to complete a 14-day course. <h3>Conclusions:</h3> Syphilis is commonly known as a great imitator; it is a treatable condition so it should not be missed. We need to be more cognizant of this diagnosis when evaluating patients with temporal lobe involvement on MRI, lymphocytic pleocytosis and hypoglycorrhachia. Although HSV and autoimmune diseases are the most common causes of limbic encephalitis, as presented in our case, syphilis testing should be considered. <b>Disclosure:</b> Dr. Hu has nothing to disclose. Dr. El Helou has nothing to disclose. Nayrobi Pena Cotui has nothing to disclose. Dr. Balobaid has nothing to disclose. Dr. Montalvo Perero has nothing to disclose.

E032 Deficiency of Adenosine Deaminase 2: a rare diagnosis in a case of suspected vasculitis

Abstract Background/Aims Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive condition first described in 2014 which is characterised by vasculitis, systemic inflammation, immunodeficiency and cytopenias. The vasculitis is difficult to differentiate from polyarteritis nodosa and typically presents with recurrent strokes. It can also affect the skin and present with livedo racemosa. Clinical presentation varies widely; from vasculitic manifestations which tend to present later in life to severe haematological abnormalities such as bone marrow failure which tend to present earlier in life. Treatment with TNF inhibitors reduces the risk of additional strokes and controls inflammation in the presence of vasculitis but is not very effective against bone marrow failure. Methods We present the case of a 44-year-old gentleman who was being investigated for possible vasculitis by the rheumatology team in view of a history of Raynaud’s, 20-year history of recurrent leg ulcers and a previous pontine infarct. He presented acutely to the emergency department with numbness below the midthoracic level, weakness of his lower limbs and hands and urinary retention. His symptoms had progressed over a period of a few hours. On examination power was 4/5 on the MRC power scale for shoulder abduction and elbow flexion, 2/5 for elbow extension, 3/5 for wrist extension and 1/5 for finger extension. Power was 1/5 on his lower limbs. Sensation to pain was reduced with a T6 sensory level. Proprioception and vibration sense were intact. Upper limb reflexes were brisk. Knee jerks and left ankle jerk were difficult to elicit. Plantars were downgoing. Cranial nerves were normal. Results Bloods showed a white cell count of 6.7x109/l, haemoglobin of 96g/l (microcytic), platelets of 243x109/l, creatinine 119μmol/l (baseline 85μmol/l) and CRP of 42.9mg/l. Vitamin B12 was 200ng/l and folate levels were 2.2μg/L. ANA, ANCA, cryoglobulins and hepatitis serology were negative. MRI brain showed a 4mm area of hyper-density in the left pons. MRI whole spine was unremarkable. CSF showed normal protein, white cell count and glucose level. The patient was transferred to a tertiary neurology centre and a diagnosis of anterior spinal cord infarction was made. A nerve biopsy was performed which showed evidence of vasculitis and he was pulsed with methylprednisolone and commenced on high dose oral steroids. Genetic testing showed a pathogenic mutation in the adenosine deaminase 2 gene. He is currently awaiting to commence treatment with TNF inhibitors. Conclusion We conclude that DADA2 is an important differential in a young patient with suspected vasculitis especially in the presence of infarction. Identification of DADA2 allows initiation of treatment with TNF inhibitors which reduces the risk of additional strokes. Disclosure M. Xenophontos: None. J. Gan: None. A.C. Seneviratne: None.

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA.Case presentationWe report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy.ConclusionTo the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

Unilateral Eyelid Angioedema: An Atypical Manifestation in Childhood IgA Vasculitis

Immunoglobulin A (IgA) vasculitis (Henoch–Schönlein purpura) is an immune-mediated small vessel vasculitis, in which edema of the nondependent areas of the body, including the face and scalp is a rare cutaneous finding, found mostly in children &lt;2 years of age. We report a case of a 7-year-old girl presenting with unilateral eyelid angioedema as a manifestation of IgA vasculitis. Early diagnosis and treatment are necessary, as the risk of renal complications increases with the incidence of angioedema.

Kawasaki like illness in COVID versus Kawasaki disease in pre-COVID era

Background: In children and adolescents, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mostly responsible for mild respiratory symptoms, in contrast with severe forms reported in adults. An association between the disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), and late manifestations of vasculitis has been increasingly suspected. Method: All children and adolescents (aged ≤18 years) who were diagnosed with Kawasaki disease (KD) and KD shock syndrome (KDSS) as per AHA and Kanegaye et al criteria. From each patient we obtained at least two nasopharyngeal swabs to test for SARS-CoV-2 using reverse transcription- polymerase chain reaction (RT-PCR). We also took blood samples to test for IgG antibodies against SARS-CoV-2. Results: Leucocytosis was found in majority with median leucocyte count of 10100 predominant neutrophila. Inflammatory markers D dimer, serum ferritin and fibrinogen level were raised. The 43% patients had coronary artery aneurysm. The 75% patient had some form of Left ventricular systolic dysfunction. All patients received IVIG while 13 patients received both IVIG and methyl predinisolone. Ionotropes were used in 68%. Two patients received tocluzumab. Conclusions: In this study we found increased incidence of Kawasaki like illness temporally associated with COVID-19. Older age of presentation with more atypical presentation.

C-Reactive Protein Levels Are Associated with Complement C4 Deposits and Interstitial Arteritis in ANCA-Associated Renal Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis in case of kidney involvement, representing a major denominator of AAV mortality. Innate immunity with complement system activation is increasingly recognized in the pathogenesis of AAV and as an attractive therapeutic target. Although C-reactive protein (CRP) was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self-determinants. Elevated baseline CRP at disease onset of AAV has already been described as a determinant of poor long-term outcomes. However, its clinical implications at disease onset of AAV, with respect to vasculitis manifestations and complement system activation that might also affect long-term outcomes, remain elusive. CRP levels were retrospectively analyzed in 53 kidney-biopsy-confirmed cases of ANCA-associated renal vasculitis; a total of 138 disease controls were also evaluated. Univariate and multivariate regression analysis was performed on clinicopathological parameters associated with CRP levels in ANCA-associated renal vasculitis. Results: Compared to disease controls, CRP elevation was common in ANCA-associated renal vasculitis and associated with de novo disease (p = 0.0169), critical illness (p = 0.0346), and severe deterioration of kidney function (p = 0.0167), independent of extrarenal disease manifestations. As confirmed by multiple regression analysis, CRP levels were correlated with active lesions predominated by interstitial arteritis in renal vasculitis, specifically with MPO-ANCA seropositivity (p = 0.0017). Based on analysis of systemic complement system activation and intrarenal complement deposits, CRP elevation was correlated specifically with complement C4 deposits in interstitial arteries in the subgroup with myeloperoxidase (MPO)-ANCA seropositivity (p = 0.039). Finally, this association was independent of systemic complement system activation, as reflected by the consumption of respective complement components. Here, we expand our current understanding of CRP in ANCA-associated renal vasculitis not only as an inflammatory marker, but potentially also as being involved in the pathogenesis of kidney injury by interaction with the complement system.

Patterns of Interstitial Lung Disease and Prognosis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Background: Interstitial lung disease (ILD) is a common pulmonary manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Objectives: We aimed to clarify the clinical predictors of mortality in a cohort of patients with AAV-related ILD (AAV-ILD). Method: We retrospectively identified AAV-ILD patients seen at Peking University First Hospital from January 2010 to June 2020 and manually screened for study inclusion. Baseline computed tomography (CT) images were further classified as nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), and unclassified ILD. Disease characteristics and other pulmonary findings including pulmonary function test and bronchoalveolar lavage (BAL) were also evaluated. Multivariable Cox regression analysis was performed to identify clinical predictors of mortality. Results: The cohort included 204 patients with AAV-ILD, 152 had UIP on CT (AAV-UIP), 39 had NSIP on CT (AAV-NSIP), 3 had OP, and 10 had unclassified ILD. Microscopic polyangiitis was more prevalent in patients with UIP, while granulomatosis with polyangiitis was more common in the NSIP and OP groups, and eosinophilic granulomatosis with polyangiitis was more frequent in patients with unclassified ILD. ILD diagnosis before AAV was more common in patients with either UIP or NSIP patterns. During the median follow-up of 40 months, 44 (21.6%) patients died. One- and 5-year overall survival rates were 88.2% (95% CI, 83.7–92.7%) and 81.0% (95% CI, 74.9–87.1%) for the entire cohort. Patients with UIP patterns had the worst prognosis, while those with NSIP patterns had the best long-term outcome. Specifically, patients with UIP patterns had an approximately 5-fold risk of death compared to those with NSIP. After controlling for potential confounding factors, we observed that each 10% increase in the BAL fluid neutrophil percentage was associated with nearly a 20% increased risk of death (HR 1.195, 95% CI 1.018–1.404). Conclusions: Clinical characteristics and survival differ between subgroups defined by CT patterns. BAL fluid neutrophilia is an independent predictor of mortality among AAV-ILD patients, and therefore, the clinical utility of BAL at the time of AAV diagnosis should be considered.

Incidence, risk factors, and severity of clinical manifestations of skin vasculitis in patients with HCV- and HCV/HIV-infection

Introduction. Several viruses including hepatitis C virus (HCV) and human immunodeficiency virus (HIV) can induce vasculitis.Aim. We aimed to study the incidence, risk factors, and severity of skin vasculitis in patients with HCV and HCV/HIV coinfection.Patients and Methods. The study group included 331 patients (254 patients with HCV and 77 patients with HCV/HIV coinfection) referred to a specialized hepatology center for antiviral therapy of HCV infection.Results. Skin vasculitis was found in 21% (95% CI: 17–25%) of cases, n = 69/331. Skin vasculitis was observed in in 20% of patients infected with HCV (95% CI: 15–25%) and in 25% of HIV/HCV co-infected patients (95% CI; 16–35%), χ2 = 0,892, р = 0,345. Most patients with vasculitis infected with HCV had cryoglobulinemia (94%, n = 47/50), meanwhile, in HIV/HCV co-infected patients, cryoglobulinemia was found in 63% cases (n = 12/19), χ2 = 10.568, р = 0.001. Multiple regression analysis showed that skin vasculitis was related with cryoglobulinemia (OR = 6,928, 95% CI: 3.245–14.790, р &lt; 0.001), liver cirrhosis (OR = 2.015, 95% CI: 1.062–3.824, р = 0.032), duration of overt HCV infection (OR = 1.057, 95% CI: 1.021–1.094, р = 0.002), patients age (OR = 1.029, 95% CI: 1.002–1.057, р = 0.033) and inversely related with plasma alanine transaminase (OR 0.433, 95% CI: 0.229–0.820, р = 0.010). The statistical model was normalized for gender, HIV-positivity and bilirubin levels, and regression equation constant was 4.398 (p &lt; 0.001). The intensity of skin rashes was comparable in HCV infected and HCV/HIV co-infected patients (χ2 = 6.741, р = 0.081), and was highly correlated with cryoglobulin levels both in HCV infected (r = 0.788, p &lt; 0.001), and HCV/HIV co-infected patients (r = 0.909, p = 0.001).Conclusion. Skin vasculitis was found in 20–25% of cases among patients with HCV infection and HCV/HIV co-infection. Cryoglobulinemia was the main factor associated with skin vasculitis, and severity of skin lesions was closely related with cryoglobulin levels.

Cavitating lung disease is not always due to tuberculosis! Wegener’s granulomatosis with mycetoma with deep vein thrombosis lower limb: Case report with review of literature

Pulmonary tuberculosis is most common cause for bilateral pulmonary cavities with constitutional symptoms in India being endemic and more prevalent nature of disease, irrespective of microscopy or nucleic acid amplification test abnormalities. Pulmonary manifestations of systemic vasculitis have very diverse involvement ranging from nodule, consolidation, and cavitation. In this case report, 49-year female, presented with constitutional symptoms with lung parenchymal consolidations progressed to cavitation’s and started empirical anti-tuberculosis treatment without mycobacterial microscopic or genome documentation in sputum with clinical or radiological worsening. Bronchoscopy workup is inconclusive and tropical screen for bacterial, TB, and malignancy were negative and fungal yield aspergillus colonization. Vasculitis workup done in presence of clinical and radiological worsening documented PR3-ANCA positive with very highly raised titers. We have started on steroids, cyclophosphamide with antifungals and clinical response documented with near complete resolution of shadows in 24 weeks. She had developed DVT (deep vein thrombosis) lower limb during course of illness and documented excellent response to anticoagulation. DVT prophylaxis is must in all cases taking steroids with decreased daily activities to prevent fatal cardiovascular complications.

Steroid-Responsive Cerebral Vasculitis in Systemic Lupus Erythematosus with Sulcal Hyperintensities

The clinical manifestations of cerebral lupus vasculitis have a wide spectrum of severity which can result in different prognoses. Therefore, its diagnosis and treatment remain challenging without specific guidelines. A 49-year-old woman with systemic lupus erythematosus presented with transient left side paresthesia and dysarthria lasting 20 minutes. Brain magnetic resonance imaging (MRI) showed a multifocal diffusion restriction and sulcal hyperintensities in the right middle cerebral artery region. Brain magnetic resonance angiography (MRA) showed multifocal steno-occlusive lesions at her intracranial arteries. Because she only showed transient symptoms, aspirin (100 mg/day), atorvastatin (20 mg/day) and an increased dose of prednisolone (5 mg/day to 10 mg/day) were started, on the suspicion of cerebral lupus vasculitis. Brain MRIs/MRAs renormalized after four months without any recurrence. Cerebral lupus vasculitis manifests diverse clinical and neuroimaging characteristics. Although brain image demonstrates devastating features, tailored immune therapy should be selected based on the severity of the patient’s symptoms.

Ocular manifestations of ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) is a group of multisystem diseases that can have several ocular manifestations. There are published data on ocular manifestations of granulomatosis with polyangiitis (GPA), but few for eosinophilic granulomatosis with polyangiitis (EGPA) or microscopic polyangiitis (MPA). There is little information concerning chronicity, complications, and association with other cranial manifestations of AAV. This study retrospectively analysed longitudinal multicentre cohorts of individuals with AAV followed between 2006 and 2022. Data included diagnosis, demographics, cranial manifestations of disease, presence of manifestations at onset of disease and/or follow-up, and ocular complications of disease. Univariate and multivariable logistic regression analysis assessed associations across disease manifestations. Data from 1441 patients were analysed, including 395 with EGPA, 876 with GPA, and 170 with MPA. Ocular manifestations were seen within 23.1% of patients: 39 (9.9%) with EGPA, 287 (32.7%) with GPA, and 12 (7.1%) with MPA at any time in the disease course. There were more ocular manifestations at onset (n = 224) than during follow-up (n = 120). The most common disease-related manifestations were conjunctivitis/episcleritis and scleritis. In multivariable analysis, dacryocystitis, lacrimal duct obstruction, and retro-orbital disease were associated with sinonasal manifestations of GPA; ocular manifestations were associated with hearing loss in MPA. The most common ocular complications and/or damage seen were cataracts (n = 168) and visual impairment (n = 195). Ocular manifestations occur in all forms of AAV, especially in GPA. Clinicians should be mindful of the wide spectrum of ocular disease in AAV, caused by active vasculitis, disease-associated damage, and toxicities of therapy.

Physicians' perceptions about antineutrophil cytoplasmic antibody-associated vasculitis: an online survey reportin the time of the COVID-19 pandemic.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by necrotizing inflammation of small and medium-size vessels that often manifest with devastating multi-organ effects. They present with a myriad of systemic features and require potent immunosuppression. Since they are uncommonly encountered in clinical practice, it is necessary to understand physicians' knowledge and perceptions about this group of diseases. An online questionnaire was designed featuring 28 questions based on relevant global practice guidelines, recommendations, and previous online surveys on AAV. The questionnaire was validated by a core group of specialists with an interest in AAV. It was shared via social networking sites and entries were restricted to physicians. Only completed entries were analyzed with descriptive statistics. A total of 113 respondents from 21 different countries responded of whom the commonest were rheumatologists, internists, and general practitioners. Forty-five(40%) ran clinics dedicated to AAV patients as a part of their practice. They commented on organs involved in AAV; vasculitis secondary to infections, drugs or other rheumatic diseases; various tests useful for AAV diagnosis; and drug choices for induction and maintenance. They mentioned their experience regarding COVID-19 in AAV patients as well as vasculitic manifestations of COVID-19. Various methods to mitigate cardiovascular risks in AAV were mentioned. Finally, the respondents indicated how medical education needed to be strengthened to increase awareness and knowledge regarding AAV. This survey helped to inform about various perceptions regarding AAV across countries, including current practices and recent evolution of management. It also provided information on treatment of the COVID-19 in AAV patients. This survey showed that there is still a lack in understanding the prevalent definitions and there is gap between guidelines and current practice. Key Points • Perception about ANCA-associated vasculitis differ across countries. • The number of cases encountered across 21 different countries are limited implying a need for multi-national cooperation to study this disease further. • The COVID-19 pandemic has changed the approach towards ANCA-associated vasculitis by the various clinicians.