Positive Vasculitis Research Articles

Compromiso gastrointestinal inusual en paciente pediátrico con vasculitis asociada a anticuerpos anticitoplasma de neutrófilos. Reporte de un caso

Vasculitis is characterized by presenting inflammation of the wall of blood vessels, one type of these diseases are those associated with anti-neutrophil cytoplasm antibodies. They usually occur in adulthood and are rare in childhood. The disease generally affects the lung, kidney, and skin, with gastrointestinal involvement being rare. Here we describe the case of a pediatric patient with gastrointestinal bleeding secondary to ANCA positive vasculitis. Endoscopy revealed patchy erythematous lesions and wall hematoma at the level of the colon. Although we report a fairly infrequent clinical condition, it is not without complications. We believe it is appropriate to suspect it, first of all, intestinal involvement where the underlying inflammatory process is not clear, even more so when it involves other organs.

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Clinical features and outcomes of elderly patients with antineutrophil cytoplasmic antibody-positive vasculitis: a single-center retrospective study.

BackgroundWe aimed to investigate the clinical characteristics and outcomes of patients aged ≥65 years with antineutrophil cytoplasmic autoantibody (ANCA)-positive ANCA-associated vasculitis (AAV) in Korea.MethodsSeventy patients diagnosed with ANCA-positive AAV from 2006 to 2019 at a single center were analyzed and categorized into younger (aged <65 years) or elderly (aged ≥65 years) groups. Initial induction treatments were investigated according to age group. All-cause mortality and kidney outcomes were evaluated.ResultsAfter categorization by age, 34 (48.6%) and 36 patients (51.4%) were in the younger and elderly groups, respectively. In the elderly group, more patients were treated with oral cyclophosphamide (CYC) (30.6%) than with intravenous CYC (19.4%). During a median follow-up of 14.6 months (range, 3.0–53.1 months), 13 patients died (elderly group: 11 patients, 84.6%). In the elderly group, older age (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09–1.90; p = 0.01), lower hemoglobin (HR, 0.21; 95% CI, 0.08–0.60; p = 0.003), and higher serum creatinine level (HR 14.17; 95% CI, 1.29–155.84; p = 0.03) were significant risk factors for all-cause mortality after adjustment. Oral CYC + steroid treatment was associated with decreased all-cause mortality compared to untreated induction immunosuppressants (HR, 0.01; 95% CI, 0.001–0.47; p = 0.02). Kidney failure or kidney recovery outcomes were not significantly different between the younger and elderly groups.ConclusionPatients aged ≥65 years had higher mortality rates than younger patients, and mortality was associated with older age, lower hemoglobin, higher serum creatinine level, and nontreatment compared to oral CYC + steroids.

A Worldwide Pharmacoepidemiologic Update on Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in the Era of Targeted Therapies.

The literature supporting the role of a specific drug in the onset of drug-induced antineutrophil cytoplasmic antibody-associated vasculitis (AAV) mainly relies on case reports or short series and implicates old treatments. The advent of new treatments may have modified the epidemiology of these adverse drug reactions. This study was undertaken to update the list of drugs associated with AAV by using a pharmacovigilance-based data mining approach. We collected data on adverse drug reactions reported using the Medical Dictionary for Regulatory Activities preferred term "anti-neutrophil cytoplasmic antibody positive vasculitis" up to November 2020 from the World Health Organization pharmacovigilance database (VigiBase). For each retrieved drug, a case-noncase analysis was performed, and disproportionate reporting was calculated by using the information component (IC). A positive IC025 value, which is the lower end of the 95% credibility interval, was considered significant. A total of 483 deduplicated individual case safety reports of drug-induced AAV involving 15 drugs with an IC025 >0 were retrieved. Of the individuals with drug-induced AAV for whom data on sex were available (n = 371), 264 (71.2%) were women. The median age at onset of drug-induced AAV was 62 years (quartile 1 [Q1]-Q3 45-72 years), and the median time from the introduction of the suspected drug to the onset of drug-induced AAV was 9 months (Q1-Q3 1-36 months). Drug-induced AAV was considered serious in 472 (98.1%), and was fatal in 43 (8.9%), of 481 cases. The drugs associated with the highest disproportionate reporting were hydralazine, propylthiouracil, thiamazole, sofosbuvir, minocycline, carbimazole, mirabegron, and nintedanib. Our findings strengthen the evidence of an association of AAV with previously suspected drugs, but also identify 3 new drugs that may cause drug-induced AAV. Particular attention should be given to these drugs by prescribers and in experimental studies.

Porcine Desiccated Thyroid Extract Associated Dual Positive ANCA Vasculitis

Porcine Desiccated Thyroid Extract Associated Dual Positive ANCA Vasculitis

Maintenance of Remission and Risk for Relapse in Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Kidney Involvement

Maintenance of Remission and Risk for Relapse in Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Kidney Involvement

Clinical significance of large unstained cell count in estimating the current activity of antineutrophil cytoplasmic antibody-associated vasculitis.

We investigated whether large unstained cell (LUC) count could estimate the current high activity according to Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody (ANCA) positive ANCA-associated vasculitis (AAV). We retrospectively reviewed the medical records of 176 immunosuppressive drug-naïve patients with ANCA positive AAV. Clinical and laboratory data at diagnosis, including LUC count, were collected. High BVAS was defined as the highest tertile of BVAS (BVAS≥15) in this study. The median age was 61.0years, and 64.8% were female. The median LUC count was 60.0mm3 , and LUC was detected in 106 patients. LUC count was significantly correlated with BVAS, age, white blood cell count, haemoglobin, platelet count, serum albumin, erythrocyte sedimentation rate and C-reactive protein. Overall, the median BVAS in AAV patients with LUC positivity was significantly higher than that in those without (14.0 vs 10.0). When the cut-off of LUC count for the current high BVAS was set as BVAS≥15mm3 , AAV patients with LUC count≥15mm3 had a significantly higher risk for the current high BVAS than those with LUC count<15mm3 (relative risk 2.596). However, in the multivariable linear and logistic regression analyses, LUC did not seem to estimate the current BVAS independently among clinical and laboratory variables. LUC count was significantly correlated with the current BVAS and LUC count≥15mm3 could estimate the current high BVAS in patients with ANCA positive AAV.

POS0118 A WORLDWIDE PHARMACOEPIDEMIOLOGICAL UPDATE OF DRUG-ASSOCIATED ANCA-ASSOCIATED VASCULITIS AT THE TIME OF TARGETED THERAPIES

Background:Several pharmacological classes are involved in drug-associated anti-neutrophil cytoplasmic antibody-associated vasculitis (DA-AAV). However, the literature data supporting the role a drug in the onset of DA-AAVs mainly rely on case reports or short series and implicate old treatments. Moreover, the advent of new treatments, including targeted therapies, may have modified the epidemiology of these adverse drug reactions (ADRs).Objectives:To update this list by using a pharmacovigilance-based data mining approach.Methods:We collected data on ADRs reported with the MedDRA preferred term “Anti-neutrophil cytoplasmic antibody positive vasculitis” up to November 2020, from the World Health Organization pharmacovigilance database. For each retrieved drug, a case/noncase analysis was performed, and disproportionate reporting was calculated by using the information component (IC). A positive IC025 value, which is the lower end of the 95% credibility interval, was considered significant.Results:A total of 483 deduplicated individual case safety reports of DA-AAV involving 15 drugs with an IC025&gt;0 were retrieved. DA-AAV occurred in 264 (71.2%, n=371) women, the median age at onset was 62 years [45-72], and the median time to onset between the introduction of the suspected drug and DA-AAV was 9 months [1-36]. DA-AAV occurrence was considered serious in 472 (97.7%, n=481) cases and fatal in 43 (8.9%) cases. The drugs associated with the highest disproportionate reporting were hydralazine, propylthiouracil, thiamazole, sofosbuvir, minocycline, carbimazole, mirabegron, and nintedanib (Table 1).Table 1.List of the 15 drugs associated with ANCA-associated vasculitis in the World Health Organization pharmacovigilance database with significant disproportional reporting, sorted by decreasing IC025.DrugNobservedNfatal (%)IC025 / ICROR [95%CI]Delay (in days) between the introduction of the drug and AAV, median [Q1-Q3] (n available)Hydralazine20819 (9%)8.2 / 8.42683.5 [2269.3-3173.3]1277 (n=1)Propylthiouracil1084 (4%)7.2 / 7.51201.5 [974.8-1480.9]1003 [425-1959] (n=19)Thiamazole405 (13%)5.2 / 5.6138.7 [100.7-191.1]411 [58-966] (n=6)Sofosbuvir4604.9 / 5.374.6 [55.3-100.8](n=0)Minocycline1703.8 / 4.672.4 [44.7-117.3](n=0)Carbimazole602.0 / 3.444.9 [20.1-100.4]92 (n=1)Mirabegron72 (29%)1.5 / 2.711.1 [5.3-23.3]291 [289-415] (n=3)Nintedanib62 (33%)1.4 / 2.814.2 [6.3-31.7]56 [36-132] (n=4)Penicillamine41 (25%)1.4 / 3.1170.3 [63.5-456.3](n=0)Influenza vaccine292 (7%)1.3 / 1.94.1 [2.8-6.0]24 [20-26] (n=7)Allopurinol72 (29%)1.2 / 2.48.0 [3.8-16.8](n=0)Rifampicin72 (29%)0.6 / 1.94.7 [2.2-9.8](n=0)Peginterferon alfa-2b400.3 / 2.17.0 [2.6-18.6]98 (n=1)Montelukast44 (100%)0.2 / 1.95.8 [2.2-15.5](n=0)Rosuvastatin600.1 / 1.53.4 [1.5-7.5](n=0)IC: information component; ROR: reporting odds ratio; CI: confidence interval; AAV: ANCA-associated vasculitisConclusion:This study strengthens the previously suspected association but also identifies 3 new drugs that may cause DA-AAV. Particular attention should be given to these drugs by prescribers and in experimental studies.Disclosure of Interests:None declared

P208 A case of double positivity

Abstract Background/Aims In the absence of renal or lung involvement, the investigation of small vessel vasculitis does not routinely include checking of anti-glomerular basement membrane (GBM) antibodies. We present a patient with an MPO-ANCA positive vasculitic neuropathy who later developed anti-GBM positive glomerulonephritis. We review the literature on patients who are “double-positive” for ANCA and GBM antibodies and speculate on the utility of routinely screening all vasculitis patients for GBM antibodies in the absence of manifestations of Goodpasture’s syndrome. Methods We describe a 70 year old female who presented feeling generally unwell with reduced mobility due to discomfort in her feet. Examination was unremarkable, except for reduced temperature and joint position sense in the feet. CRP was elevated and she was found to have a weakly positive MPO titre of 32. She was treated as an MPO-ANCA positive vasculitis and neuropathy with steroids and Mycophenolate Mofetil, with a good clinical and biochemical response. Fifteen months into her treatment, routine monitoring revealed an acute kidney injury with a creatinine of 459 umol/l from a baseline of 88. Anti GBM titres were requested for the first time as part of the renal screen. MPO antibody titres were only 9, but GBM antibody titres were markedly elevated (&amp;gt;200). Renal biopsy showed focal necrotising glomerulonephritis, in keeping with anti-GBM disease. She was treated with steroids, cyclophosphamide and plasma exchange by the renal physicians. She remains dialysis dependant. Results In our patient, GBM antibodies were only requested once she developed relevant clinical manifestations of anti-GBM disease. This in contrast to nephrology practise, where ANCA and GBM antibodies are routinely requested simultaneously in the context of nephritis. It could be speculated that if the GBM antibody status had been detected sooner, we may have altered her management and possibly improved her disease course. Anti-GBM disease and ANCA-associated vasculitis are both rare conditions. However, co-existence of the two uncommon diseases in individual patients is well-described and more than chance occurrence. A study showed that 5% of ANCA-positive cases were also positive for anti-GBM antibodies, while one-third of anti-GBM positive samples had detectable ANCA. Multiple studies have shown that low level ANCA antibodies develop months to years before onset of anti-GBM disease, as seen in our patient as well.The dominant disease phenotype in double positive patients is anti-GBM disease rather than vasculitis. It is very rare for isolated anti-GBM disease to relapse. In contrast, half of double positive patients experience disease relapse and therefore, require long-term follow-up and maintenance immunosuppression. Conclusion Awareness of this double positive phenomenon is important. Rheumatologists do not routinely check anti-GBM in all vasculitis. This case highlights the importance of doing so, especially in atypical presentation of vasculitis or in relapse and refractory disease. Disclosure S. Khalid: None. J. Li: None. S. Young Min: None.

POS-236 A SINGLE CENTRE RETROSPECTIVE ANALYSIS OF TREATMENT OUTCOMES IN RENAL VASCULITIS PATIENTS

Percentage of normal glomeruli at renal biopsy has been shown to be an independent risk factor for end-stage renal disease (ESRD). A risk stratification scoring system has recently been devised for patients with antineutrophil cytoplasmic antibody (ANCA) positive renal vasculitis based on three clinicopathological features: percentage of normal glomeruli, tubular atrophy and eGFR at the time of biopsy. Patients are categorised into high, medium and low risk according to their 'Renal Risk Score'.

POS-156 MANAGEMENT AND OUTCOMES OF ANCA ASSOCIATED VASCULITIS AT A TERTIARY HEALTHCARE FACILITY

Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare disorder with annual incidence estimated to be around 1.3 per 100,000 population. Renal involvement is one of the main predictors of mortality and morbidity, with approximately 30% of patients with renal involvement progressing to ESRD after 5 years. Renal biopsy can provide a definite diagnosis, and may predict the renal prognosis in AAV. Limited data is available on its management and outcomes, thus we aim to assess this at our tertiary care renal facility. This was a retrospective cohort study. We included patients with a documented diagnosis of ANCA positive vasculitis between 1st of January 2012 to the 31st December 2017, with a follow up period until 31st December 2019. Using a standardized data collection form we recorded the number of patients who had a renal biopsy, the induction and maintenance therapies used, along with relapse induction and maintenance therapies. At the end of the follow-up period outcomes were divided into progression to end-stage renal disease (ESRD), death, established chronic kidney disease (CKD), and preservation of renal function. Data of thirty-six patients were included in the final study. The patient baseline characteristics are listed in Table 1. Thirty-two patients (94.1%) had a documented renal biopsy. The majority of patients (66.7%) had cyclophosphamide for induction, followed by rituximab (19.4%). Seven patients (19.4%) had a documented relapse during the study period, 4 MPO+ and 3 PR3+. Six patients (85.7%) had rituximab as an induction therapy for relapse. The majority of patients were on azathioprine (61.1%) as maintenance therapy after induction. This was similar to the maintenance therapy used after relapse (57.1%). Progression to ESRD occurred in 11 (30.6%), death in 4 (11.1%), established CKD in 15 (41.7%), and preservation of renal function in 6 (16.7%) patients by the end of the follow up period. While cyclophosphamide remains the choice of induction immunosuppresion therapy, we favour rituximab as an induction agent in relapse of AAV. However despite aggressive immunosuppresion therapy the incidence of ESRD and death remains high in these patients. The current management and outcomes are comparable to present international guidelines and cohorts. We look forward to new updates and therapies to improve outcomes in AAV.

Advances in the genomics of ANCA-associated vasculitis-a view from East Asia.

Recent genome-wide association studies (GWAS) in populations of European ancestry have identified several susceptibility genes to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The most significant association was observed in HLA-DP variants in granulomatosis with polyangiitis and proteinase 3 (PR3)-ANCA positive vasculitis, while HLA-DQ variants were strongly associated with microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA positive vasculitis (MPO-AAV). In non-HLA genes, SERPINA1, PRTN3 and PTPN22 were identified as susceptibility genes to AAV. The observations in GWAS suggested the presence of shared and non-shared susceptibility genes among AAV subsets. Epidemiological features of AAV are strikingly different in the East Asian populations; the proportions of MPO-AAV among total AAV, MPO-ANCA positive patients among GPA, and patients with interstitial lung disease among total AAV are considerably higher in Japan as compared with Europe. Such population differences suggest the critical role for genetic background behind these conditions. Although no GWAS has been reported in the Asian populations so far, the association of HLA-class II alleles with MPA and MPO-AAV was identified. Future genomics studies on AAV, especially from Asian populations, will provide valuable information to elucidate the molecular mechanisms and to identify molecular targets for AAV.

Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis.

In vasculitis disorders, inflammation affects blood vessels. Granulomatosis with polyangiitis (GPA) is a chronic systemic vasculitis distinguished by the presence of anti-proteinase-3 autoantibodies (anti-PR3). In this study we analyzed the molecular signature of human umbilical endothelial cells (HUVECs) in response to neutrophil-derived extracellular vesicles (EVs). EVs were obtained from anti-PR3-activated neutrophils, purified and characterized by flow cytometry, nanoparticle tracking and miRNA screening. HUVECs were stimulated with EVs and miRNA/mRNA expression was measured. Cell culture media proteins were identified by antibody microarrays and selected cytokines were measured. Comparison of differentially expressed miRNAs/mRNAs between non-stimulated and EV-stimulated HUVECs revealed two regulatory patterns. Significant up-regulation of 14 mRNA transcripts (including CXCL8, DKK1, IL1RL1, ANGPT-2, THBS1 and VCAM-1) was accompanied by 11 miRNAs silencing (including miR-661, miR-664a-3p, miR-377-3p, miR-30d-5p). Significant down-regulation was observed for nine mRNA transcripts (including FASLG, CASP8, STAT3, GATA3, IRAK1 and IL6) and accompanied by up-regulation of 10 miRNAs (including miR-223-3p, miR-142-3p, miR-211-5p). Stimulated HUVECs released IL-8, Dickkopf-related protein 1 (DKK-1), soluble interleukin (IL)-1 like receptor-1 (ST2), growth differentiation factor 15 (GDF-15), angiopoietin-2, endoglin, thrombospondin-1 and vascular adhesion molecule-1 (VCAM-1). Moreover, transfection of HUVECs with mimics of highly expressed in EVs miR-223-3p or miR-142-3p, stimulated production of IL-8, ST2 and endoglin. Cytokines released by HUVECs were also elevated in blood of patients with GPA. The most increased were IL-8, DKK-1, ST2, angiopoietin-2 and IL-33. In-vitro stimulation of HUVECs by neutrophil-derived EVs recapitulates contribution of endothelium in autoimmune vasculitis. Proinflammatory phenotype of released cytokines corresponds with the regulatory network of miRNAs/mRNAs comprising both EVs miRNA and endothelial cell transcripts.

18660 Increased systemic symptoms in patients with positive direct immunofluorescence of skin biospies with Henoch-Schonlein purpura/IgA vasculitis: A retrospective chart review

Direct immunofluorescence (DIF) of skin biospies is an important tool in the diagnosis of Henoch-Schonlein purpura (HSP)/IgA vasculitis. In a retrospective chart review of IgA positive vasculitis patients seen by dermatology over the previous 5 years, we sought to determine whether presence of systemic symptoms classically seen in HSP correlated with a higher risk of renal disease. A total of 14 out of the 22 patients (63.63%) who underwent DIF staining of a skin biopsy tested positive for IgA. Of the patients that were positive for IgA on biopsy, 64.3% reported gastrointestinal symptoms, 28.6% had musculoskeletal involvement, and 14.3% reported fever.

Association of TERT and DSP variants with microscopic polyangiitis and myeloperoxidase-ANCA positive vasculitis in a Japanese population: a genetic association study

BackgroundInterstitial lung disease (ILD) is a severe complication with poor prognosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Prevalence of AAV-associated ILD (AAV-ILD) in Japan is considerably higher than that in Europe. Recently, we reported that a MUC5B variant rs35705950, the strongest susceptibility variant to idiopathic pulmonary fibrosis (IPF), was strikingly increased in AAV-ILD patients but not in AAV patients without ILD; however, due to the low allele frequency in the Japanese population, the MUC5B variant alone cannot account for the high prevalence of AAV-ILD in Japan. In this study, we examined whether other IPF susceptibility alleles in TERT and DSP genes are associated with susceptibility to AAV subsets and AAV-ILD.MethodsFive hundred and forty-four Japanese patients with AAV and 5558 controls were analyzed. Among the AAV patients, 432 were positive for myeloperoxidase (MPO)-ANCA (MPO-AAV). A total of 176 MPO-AAV patients were positive and 216 were negative for ILD based on CT or high-resolution CT. Genotypes of TERT and DSP variants were determined by TaqMan SNP Genotyping Assay, and their association was tested by chi-square test.ResultsWhen the frequencies of the IPF risk alleles TERT rs2736100A and DSP rs2076295G were compared between AAV subsets and healthy controls, both alleles were significantly increased in microscopic polyangiitis (MPA) (TERT P = 2.3 × 10−4, Pc = 0.0023, odds ratio [OR] 1.38; DSP P = 6.9 × 10−4, Pc = 0.0069, OR 1.32) and MPO-AAV (TERT P = 1.5 × 10−4, Pc = 0.0015, OR 1.33; DSP P = 0.0011, Pc = 0.011, OR 1.26). On the other hand, no significant association was detected when the allele frequencies were compared between MPO-AAV patients with and without ILD.ConclusionsUnexpectedly, TERT and DSP IPF risk alleles were found to be associated with MPA and MPO-AAV, regardless of the presence of ILD. These findings suggest that TERT and DSP may be novel susceptibility genes to MPA/MPO-AAV and also that some susceptibility genes may be shared between IPF and MPA/MPO-AAV.

OVERLAP SYNDROME AND MYELOPEROXIDASE-POSITIVE VASCULITIS: NEW PULMONARY FINDINGS

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: We report a case of connective tissue disease-associated interstitial lung disease (CTD-ILD) in a patient with Overlap Syndrome and myeloperoxidase (MPO) positive vasculitis. We will review the disease presentation and hallmark radiologic features seen on computed tomography (CT) imaging. These specific radiologic features can be used in conjunction with laboratory markers to correctly identify the underlying etiology. CASE PRESENTATION: Our patient is a 52-year-old African American female with a past medical history of hypertension and asthma who had been complaining of dyspnea for 2 years prior to obtaining imaging studies. In March 2019, a CT chest was done and revealed bilateral anterior upper lobe fibrosis. In April 2019, she was diagnosed with Overlap Syndrome based on her symptoms of anterior uveitis and chronic polyarthritis, radiographic findings of fibrotic interstitial lung disease (ILD), and positive serology. Laboratory studies were remarkably positive for anti-nuclear antibody (ANA) speckled pattern with a titer of 1:1280, anti- ribonucleoprotein (RNP) antibody 127, and MPO 48.1 (ANCA’s unable to test). Negative studies included ds-DNA, anti-centromere, anti- scl-70, anti-cyclic citrullinated peptide, rheumatoid factor, RNA polymerase III, anti- smith antibody, anti-Ro/ SSA, anti-La/ SSB, and an extended myositis panel. She also developed pulmonary hypertension group I disease in late 2019 and was started on Selexipag. She was offered immunosuppression therapy with Mycophenolate Mofetil but unfortunately is still hesitant to start the medication due to the side effect panel. DISCUSSION: There are 3 hallmark radiologic signs that were recently observed in patients with CTD-ILD in a retrospective analysis from University of Chicago. These signs are: 1- the anterior upper lobe sign, 2- the “exuberant honeycombing sign”, 3- the straight edge sign. Our patient had all these signs present in her imaging studies; findings of which were not described in patients with MPO positive vasculitis presenting with ILD. CONCLUSIONS: We report this case to add patients with overlap syndrome and MPO positive vasculitis related ILD to the panel of previously described patients with scleroderma, rheumatoid arthritis, myositis and Sjogren’s disease. Reference #1: Chung J, Cox C, Montner S, Adegunsoya A, Oldham J, Husain A, Vij R, Noth I, Lynch D, Strek M. CT Features of the Usual Interstitial Pneumonia Pattern: Differentiating Connective Tissue Disease- Associated Interstitial Lung Disease from Idiopathic Pulmonary Fibrosis. American Journal of Roentgenology. 2018 February; 210: 307-313 Reference #2: Maillet T, Goletto T, Beltramo G, Dupay G, Jouneau S, Borie R, Crestani B and others. Usual Interstitial Pnuemonia in ANCA- associated vasculitis: A poor prognostic factor. Journal of Autoimmunity. 2019 July. DISCLOSURES: No relevant relationships by ALAA ABU SAYF, source=Web Response No relevant relationships by Guneet Ahluwalia, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 Added 05/04/2020 by Krishna Thavarajah, source=Web Response, value=speaker fees for IPF rally stockholder relationship with Medtronic Please note: $5001 - $20000 Added 05/04/2020 by Krishna Thavarajah, source=Web Response, value=stockholder

MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE PULMONARY HEMORRHAGE AND ACUTE TYPE-1 RESPIRATORY FAILURE

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Microscopic polyangiitis is one of the causes of pulmonary-renal syndrome, a grave diagnosis with high mortality rate. Pulmonary symptoms include chest pain, dyspnea, and hemoptysis, with imaging showing diffuse pulmonary infiltrates. High degree of suspicion is required for timely diagnosis and management as delay in treatment increases mortality rate. CASE PRESENTATION: 59-year-old white Caucasian male with multiple comorbidities was admitted with acute type one respiratory failure requiring intubation due to diffuse pulmonary hemorrhage. During intubation, copious bloody secretions within the airway were noted, making intubation technically difficult. Patient was not taking any anticoagulant prior to admission and prophylactic anticoagulation was not initiated due to profound anemia on admission and concerns of airway hemorrhage.His clinical course was complicated by hemorrhagic shock, ischemic hepatitis, and worsening acute kidney injury that required dialysis, patient was treated with pulse steroid therapy, erythropoeitin was given in an attempt to improve anemia. Physical examination at presentation showed diffuse bilateral coarse breath sounds on auscultation. Pertinent blood work was hemoglobin of 6.8 gm/dl, Creatinine of 2.1 mg/dl, ALT of 1369 U/L, AST of 1812 U/L, positive MPO antibody with ANCA titer of 1:40, and low C3 complement level, pulmonary-renal syndrome was suspected with hemorrhagic airway and worsening kidney injury. CT scan of chest without contrast showed diffuse bilateral ground-glass opacities. Patient's family refused blood products due to religious beliefs and had continued worsening. Unfortunately, the patient did not respond to treatment and passed away. DISCUSSION: Microscopic polyangiitis (MPA) is an ANCA positive small vessel vasculitis and one of the causes of pulmonary-renal syndrome. MPA is associated with a 90% positive ANCA antibody and causes necrotizing vasculitis of small vessels without granuloma formation. Despite appropriate management, ANCA vasculitis remains a grave diagnosis with a mortality rate of 10% at one year.Intubating a patient with suspected alveolar hemorrhage can be technically difficult, placing a large diameter ETT considered safe, elective intuabtion of non-bleeding lung if bleeding lung can be indetified using bronchoscopy. Double lumen ETT is less preferable and comes with serious consequences of poor positioning and limiting bronchoscopy due to smaller-diameter lumen.Patients who declines blood transfusion can be challenging. Minimizing blood loss, reducing blood draws as well as optimizing RBC cell production along with reducing oxygen demand, improving oxygen delivery and using erythyroipesis stimulating agents have been used to improve anemia in such patients. CONCLUSIONS: Clinicians should be aware of the possibility of pulmonary-renal syndrome in a patient presenting with hemoptysis, hypoxia, and renal impairment. Reference #1: https://www.ncbi.nlm.nih.gov/pubmed/25984050 Reference #2: https://www.ncbi.nlm.nih.gov/pubmed/32185342 Reference #3: https://www.ncbi.nlm.nih.gov/books/NBK554372/ DISCLOSURES: No relevant relationships by Adel El Abbassi, source=Web Response No relevant relationships by Mahmoud El Iskandarani, source=Web Response No relevant relationships by Ibrahim Haddad, source=Web Response No relevant relationships by Sajin Karakattu, source=Web Response No relevant relationships by Lana Makahleh, source=Web Response No relevant relationships by Rasheed Musa, source=Web Response

EP28 A case of ANCA vasculitis presenting with Sjögren’s serology

EP28 A case of ANCA vasculitis presenting with Sjögren’s serology

An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report

BackgroundA number of disease processes can culminate in rapidly progressive glomerulonephritis, including pauci-immune focal segmental necrotising glomerulonephritis, usually seen with positive serum antineutrophil cytoplasmic antibodies (ANCA). Propylthiouracil (PTU) has been associated with drug-induced ANCA-associated vasculitis (AAV), with antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) present individually and together having been recognised. ‘Double-positive’ vasculitis with ANCA and anti-glomerular basement membrane (GBM) antibodies has also been reported in association with PTU treatment. We present a case of PTU-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate.Case presentationA 51-year-old man presented 2 weeks after re-commencing propylthiouracil (PTU) treatment for Graves’ disease, with a severe acute kidney injury and haemato-proteinuria. He demonstrated positive titres for autoantibodies to PR3 (76.9 IU/mL), MPO (28.8 IU/mL) and GBM (94 IU/mL). Renal biopsy demonstrated numerous glomerular crescents, widespread IgG4-positive lymphoplasmacytic infiltrate and mesangial positivity for IgA. PTU was stopped and he was treated with steroids, plasma exchange and cyclophosphamide with sustained improvement in his renal function.ConclusionsThis case of drug-induced AAV presented a unique and intriguing collection of serological and histological features. We propose that the PTU-induced AAV resulted in epiphenomena of anti-GBM antibody production and an IgG4-cell-rich tubulointerstitial infiltrate. It is uncertain whether the mesangial IgA deposition preceded or resulted from the AAV.

Eye involvement in ANCA positive vasculitis

Vasculitis is a heterogeneous group of diseases that implies the presence of necrosis and inflammation in the walls of blood vessels. The mechanisms involved are the following: immune complexes, endothelial cell antibodies, and anti-lysosomal antibodies. The immune reactions can be triggered by these mechanisms: immune complexes, endothelial cell antibodies, and anti-lysosomal antibodies. Antineutrophil cytoplasmic antibodies (ANCA) have an essential role in the following so-called ANCA+ vasculitis. Regarding this issue, we proposed to present the various aspects of ocular involvement in the ANCA+ vasculitis.