Severe Vasculitis Research Articles

Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study.

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group.MethodologyThis retrospective study was performed on SLE patients’ sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml).ResultsThe cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found “ambivalent” (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.ConclusionAnti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.

Hepatitis C virus-related cryoglobulinemic vasculitis.

Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity). CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients. In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.

IgG subclasses in cryoglobulins: link to composition and clinical manifestations

BackgroundCryoglobulins (CG) are immunoglobulins which precipitate at low temperature. The analysis of IgG subclass composition of CG is poorly reported. The aim of this study was to determine the subclasses of IgG-containing type I and mixed type II and III CG in relation to clinical manifestations.MethodsOut of a previous series of 1675 patients, inclusion criteria were a cryoprecipitate > 1 mL and a total IgG > 300 mg/L. IgG subclasses were quantified by immunoturbidimetry, rheumatoid factor (RF), and C4 by immunonephelometry. Clinical parameters were collected from hospital charts.ResultsCG samples from 86 patients were included, 10 type I CG and 76 mixed CG. Type I CG subclasses were IgG1 (6/10) and IgG2/IgG3 (4/10), never IgG4. IgG subclass in type II vs. III CG were 73.3 ± 15.2% vs. 52.5 ± 20.7% for IgG1 (p < 0.0001), 15.4 ± 8.2% vs. 25.9 ± 14% for IgG2 (p < 0.0001), 8.4 ± 12.4 vs. 21.2 ± 14% for IgG3 (p < 0.0001), and 3 ± 5.2% vs. 0.5 ± 1.2 for IgG4 (p < 0.0001). In mixed CG, the higher proportion of IgG4 was associated with RF positive CG (p = 0.01) and low C4 (p = 0.01). In type I CG, IgG1 were associated with severe vasculitis manifestations, IgG2/IgG3 with cutaneous or renal manifestations. In mixed CG, IgG2 was the only subclass associated with CG manifestations, with a higher concentration in asymptomatic (162.6 ± 29.5 mg/L) vs. symptomatic patients with cutaneous (103 ± 17.8 mg/L, p = 0.04) and neurological (108 ± 24 mg/L, p = 0.04) manifestations.ConclusionIn type I IgG CG, IgG1 was the main CG subclass associated with CG vasculitis. In mixed CG, low IgG2 concentration was linked to CG cutaneous and neurological manifestations.

A Case of Central Nervous System Metastasis of Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma Manifested as Central Nervous System Vasculitis

Introduction: Anaplastic Large Cell Lymphoma (ALCL) is a rare distinct subset of T-cell non-Hodgkin lymphomas (T-cell NHL). Anaplastic Lymphoma Kinase (ALK) positive ALCL patients are generally associated with younger age and have a better prognosis. While Central Nervous System (CNS) involvement in T-cell NHL is rare and has a dismal prognosis. There was no report about ALK + ALCL and CNS vasculitis. Case presentation: A 17-year-old boy who was diagnosed ALK + ALCL and underwent six courses of systemic chemotherapy presented as severe CNS vasculitis in the beginning, but eventually he was diagnosed CNS metastasis of ALCL by the presence of cranial nerve palsy, the demonstration of lesions on MRI and PET-CT, and Flow cytometry detection of tumor cells in Cerebrospinal Fluid (CSF). Conclusion: We first present a case of CNS metastasis of systemic ALK + ALCL accompanied with CNS vasculitis. When an ALK + ALCL patient had CNS symptoms while imaging revealed CNS vasculitis, we need to be vigilant that the patient may have CNS involvement.

HYDRALAZINE-INDUCED LUPUS VASCULITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

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: Diffuse alveolar hemorrhage (DAH) as the presenting symptom in occult vascular disease is a rare occurrence. We present an exceedingly unique case of hydralazine-induced lupus vasculitis who improved after emergent plasmapheresis and combined maintenance therapy of rituximab and steroids. CASE PRESENTATION: A 70-year-old male with hypertension and coronary artery disease, on hydralazine 100mg TID, presented to the emergency department after 10 days of dyspnea and hemoptysis. On presentation, he was hypoxic and lab work revealed an acute kidney injury, new-onset anemia, and peripheral eosinophilia. His erythrocyte sedimentation rate and C-reactive protein were markedly elevated at >145mm/h and 105.1mg/L, respectively. Urinalysis was concerning for a nephritic syndrome and CT scan of the chest suggested multifocal pneumonia with fibrotic lung pattern and ground-glass nodularity. Bronchoalveolar lavage and bronchoscopy confirmed DAH, and he was emergently started on intravenous (IV) methylprednisolone and plasmapheresis. Autoimmune workup revealed a hypocomplementemia with elevations in multiple antibodies including ANA, MPO, PR3, pANCA, anti-cardiolipin, and antiphospholipid. Renal biopsy showed acute tubular necrosis without immune complex nephropathy. His symptoms resolved after plasmapheresis, IV steroids, combined rItuximab/prednisone, and discontinuation of hydralazine. DISCUSSION: Hydralazine-induced vasculitis is a rare occurrence in medicine and presentation as DAH has not been described in the literature. This case is unique in that its antibody biomarker distribution was positive for a multitude of diagnostic markers suggestive of Lupus-associated vasculitis or ANCA-associated vasculitis. There is agreement upon initial treatment with IV glucocorticoids, however, efficacy comparing plasmapheresis, cyclophosphamide, and rituximab is debated. PLEX, PLEXIVAS, and RAVE trials suggested non-inferiority in mortality. However, these trials suggest differing secondary endpoints when comparing plasmapheresis vs non-plasmapheresis therapy in regards to end-stage renal disease and renal recovery time. PLEXIVAS also suggests a therapeutic benefit of low dose glucocorticoids combined with rituximab as maintenance therapy. CONCLUSIONS: We present a case of presumed hydralazine-induced lupus vasculitis presenting as DAH that resolved after discontinuation of the culprit agent, plasmapheresis, and maintenance therapy. Early autoimmune workup and diagnosis via bronchoscopy and renal biopsy are paramount. Further treatment guidelines for pulmonary-renal vasculitis require additional clinical trials to decipher a clear therapeutic benefit. Reference #1: McGeoch L, Twilt M, Famorca L, Bakowsky V, et al. CanVasc Recommendations for the Management of AntiNeutrophilic Cytoplasm Antibody-associated Vasculitides. J Rhematol. Jan 43(1);97-120. doi 10.3899/jrheum.150376 Reference #2: Walsh M, Merkel PA, Jayne D. The Effects of Plasma Exchange and Reduced-Dose Glucocorticoids during Remission-Induction for Treatment of Severe ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). Reference #3: Jayne DR, Gaskin G, Rasmussen N, Abramowicz D et al. Randomized trial of plasma exchange or high dose methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007 Jul; 18(7):2180-8 DISCLOSURES: No relevant relationships by Andrew Pajak, source=Web Response No relevant relationships by Shivam Thakur, source=Web Response

REFRACTORY GRANULOMATOSIS WITH POLYANGIITIS FLARE? HOW ABOUT PLASMA EXCHANGE?

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: ANCA-negative granulomatosis with polyangiitis (GPA) patients often have limited disease, but they may evolve to have life-threatening renal and pulmonary complications. In general, patients are treated with glucocorticoids and immunosuppression. We present a patient with GPA flare-up refractory to initial therapy who improved after undergoing plasma exchange. CASE PRESENTATION: A 78-year-old male with a past medical history of ANCA-negative GPA and chronic kidney disease (baseline Cr 2.5 mg/dL) presented to the hospital with dyspnea. He was discharged from the hospital one week prior where he was managed for a GPA flare-up (i.e., sudden onset bilateral lower extremity nonpalpable purpura) after he stopped methotrexate due to transaminitis. At that time, he was treated with pulse IV methylprednisolone and discharged home to begin rituximab. When he returned to the hospital with worsening dyspnea, vital signs were: BP 106/47, HR 83, RR 18, 93% O2 saturation on room air. His hospital course was complicated by copious amount of hemoptysis. Labs revealed: Hgb 5.2 g/dL (which dropped from 8.5 g/dL a week ago) and worsening renal function with BUN >150 mg/dL and Cr 5.1 mg/dL. Chest x-ray showed diffuse bilateral alveolar opacities. He had respiratory failure secondary to pulmonary hemorrhage, which led to intubation and transfusion of blood products. A decision was made to start the patient on seven sessions of plasma exchanges. The patient responded well to the therapy and was eventually extubated with pulmonary and renal function returning to baseline. DISCUSSION: In the past, plasma exchange in GPA was based upon the efficacy of removing autoantibodies in Goodpasture's syndrome. More recently, the PEXIVAS clinical trial demonstrated that plasma exchange neither reduced the risk of end-stage renal disease nor had a treatment effect on pulmonary hemorrhage in ANCA-associated vasculitis. Some statistical analyses regarding pulmonary hemorrhage had wide confidence intervals, suggesting that plasma exchange could still be useful. In addition, a kidney biopsy was not required to enter the PEXIVAS trial, making it difficult to delineate if mild or severe disease was present (as vasculitides patients often have a relapsing and remitting course). Those with minimal tubulointerstitial and glomerular scarring could theoretically benefit from plasma exchange. The patient in this case underwent plasma exchange as he was thought to be among a select subgroup whose benefits outweighed risks. CONCLUSIONS: The use of plasma exchange in vasculitides should be tailored according to the characteristics of each patient and the previous treatments that each patient received. Reference #1: 1. Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol. 2016; 3(3):122-133. DOI:10.5152/eurjrheum.2015.0043 Reference #2: 2. Walsh M et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020; 382(7):622-631. DOI: 10.1056/NEJMoa1803537 Reference #3: 3. Jayne D.R.W et al. Randomized Trial of Plasma Exchange or High-Dosage Methylprednisolone as Adjunctive Therapy for Severe Renal Vasculitis. JASN. 2007; 18(7):2180-2188; DOI: 10.1681/ASN.20070100904. Derebail V, Falk R. ANCA-Associated Vasculitis -- Refining Therapy with Plasma Exchange and Glucocorticoids. N Engl J Med. 2020; 382:671-673. DOI: 10.1056/NEJMe1917490

S2512 A Devastating Case of Hepatitis C-Induced Mixed Cryoglobulinemia

INTRODUCTION: Hepatitis C induced Mixed Cryoglobulinemia leading to rapidly progressive gangrene of all four extremities, necessitating amputations, is a rare presentation of cryoglobulinemia. It is postulated that precipitation of cold sensitive globulins in the presence of decreased vascular reserve are responsible for the occurrence of gangrene in cryoglobulinemia. CASE DESCRIPTION/METHODS: A 55-year-old male with treatment naive Hepatitis C (genotype 1a) presented to the emergency room with bilateral hand pain and diffuse purpuric rash. Physical examination showed palpable purpura and extensive gangrene affecting bilateral upper and lower extremities. Laboratory investigation revealed positive rheumatoid factor (>1,200 IU/mL), hypocomplementemia (C4 < 8.0 mg/dL), HCV RNA 2,390,000 IU/mL, and positive cryoglobulins. Cutaneous biopsy showed infiltrate with scattered small to mid-sized vessels with features of fibrin thrombi and associated vasculitis. He was diagnosed with mixed cryoglobulinemia complicated by severe cutaneous vasculitis with ischemic limbs. Plasmapheresis was initiated, however, gangrene continued to progressively worsen. He was transitioned to immunosuppressive therapy with high-dose pulse steroids followed by prednisone 60 mg daily for four weeks in combination with Rituximab. Sofosbuvir/velpatasvir was started for treatment of chronic Hepatitis C. HCV viral load was undetectable (<15 IU/mL) after one week and there was no further spread of gangrene. However, the necrotic limbs were unsalvageable, requiring serial limb amputations. DISCUSSION: There is a wide spectrum of manifestations associated with cryoglobulinemia with severe and life-threatening presentations being relatively rare (< 15% of cases). This case exemplifies a rare and devastating presentation of Hepatitis C induced mixed cryoglobulinemia. Upon literature review, this is one of the most aggressive cases of mixed cryoglobulinemia vasculitis reported thus far. There have been no other cases reported that have resulted in multiple limb amputations secondary to this extent of cryoglobulinemia. As such, this case serves to increase clinician awareness of the severe gangrene that may rapidly develop in mixed cryoglobulinemia. These cases require early recognition and aggressive treatment to prevent progression to the extent of limb amputation and even death. This highlights the necessity of universal screening for Hepatitis C and portrays the devastating effects that delayed screening and therefore delayed treatment may have.Figure 1.: Patient's left hand on initial presentation.Figure 2.: Patient's left hand weeks later, demonstrating progression of gangrene.Figure 3.: Bilateral gangrenous lower extremities.

EP08 A case of granulomatosis with polyangiitis complicated by COVID-19: challenges in diagnosis and management

EP08 A case of granulomatosis with polyangiitis complicated by COVID-19: challenges in diagnosis and management

SILENT CORONARY VASCULITIS PRECEDING FULMINANT ANTI-NEUTROPHILIC CYTOPLASMIC ANTIBODY-ASSOCIATED PULMONARY-RENAL SYNDROME: A RARE DIAGNOSTIC AND THERAPEUTIC DILEMMA

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Various forms of vasculitides ranging from benign and self-limiting to potentially life-threatening exist. Here, we report a case of a patient who harbored an asymptomatic coronary vasculitis followed by a life threatening pulmonary-renal syndrome (PRS) secondary to anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). CASE PRESENTATION: 75-year-old male presented to us with hemoptysis. Four months prior to current admission, he reported dyspnea upon exertion and was diagnosed with atrial fibrillation with rapid ventricular response for the first time. A chest x-ray was unremarkable whereas an echocardiogram revealed worsening of his aortic stenosis compared to the prior year. Elevated troponin and ST-T wave changes in EKG prompted a left heart catheterization that revealed multivessel coronary artery disease necessitating consideration of coronary artery bypass graft (CABG), surgical aortic valve replacement, and a maze procedure. During the procedures, his left atrial appendage was excised and sent for histopathological examination (HPE). Post CABG, on a routine outpatient follow up, he was found to have hyperkalemia with a potassium of 6.0 mmol/L and acute renal failure with a creatinine of 6 mg/dL (baseline creatinine of 1.0 mg/dl), prompting a second hospitalization. Bilateral renal ultrasound were unremarkable. Serum myeloperoxidase anti-neutrophilic cytoplasmic antibodies (MPO-ANCA) were elevated. Renal biopsy revealed a severe vasculitis of small vessels without any granulomas. No immune deposits were noted. He was diagnosed with AAV and was treated medically. Later in the course, he was also started on hemodialysis. Four months after the onset of his initial dyspnea patient presented with frank hemoptysis leading to a third hospitalization. CT of the chest with contrast revealed bilateral new extensive mixed ground-glass and consolidative opacities. He had developed severe PRS. Patient failed to improve with medical management; decided to undergo comfort care measures and passed away the same day. Retrospective chart review of the patient's left atrial appendage biopsy revealed vasculitis involving medium-sized myocardial and pericardial blood vessels. DISCUSSION: In this case, coronary vasculitis was a clinically silent disease with a histopathologic diagnosis whereas PRS secondary to AAV was a fulminant vasculitis with a fatal course despite therapy with pulse steroids, cyclophosphamide, plasmapheresis and hemodialysis. It is unclear whether coronary vasculitis in the patient was a prodrome to an impending serious illness or merely an incidental finding with no association to subsequent AAV. CONCLUSIONS: Vasculitis of the coronary arteries is uncommon, yet when involved in a patient portends a poor prognosis. While immunosuppression and plasma exchange therapy remain the cornerstone in management of AAV, therapeutic dilemma persists with regard to the clinically silent coronary vasculitis. DISCLOSURES: No relevant relationships by Ismael ABU LIMON, source=Web Response Speaker/Speaker's Bureau relationship with Otsuka America Pharmaceutical, Inc Please note: $1001 - $5000 Added 05/24/2020 by Arvind Garg, source=Web Response, value=Honoraria Consultant relationship with Fresenius Kidney Care Please note: $1001 - $5000 Added 05/24/2020 by Arvind Garg, source=Web Response, value=Honoraria no disclosure on file for Odalys Estefania Lara-Garcia; No relevant relationships by Ruby Maini, source=Web Response No relevant relationships by Priyanka Parajuli, source=Web Response No relevant relationships by Manjari Regmi, source=Web Response

Getting it Right the First Time: Frozen Sections for Diagnosing Necrotizing Soft Tissue Infections

BackgroundThe aim of this study was to investigate which histopathologic findings are most indicative for necrotizing soft tissue infections (NSTIs) in ambivalent cases.MethodsPatients undergoing surgical exploration for suspected NSTIs with obtainment of incisional biopsies for histopathological assessment were included from January 2013 until August 2019. The frozen sections and formalin-fixed paraffin-embedded (FFPE) samples were retrospectively re-assessed. The primary outcome was the discharge diagnosis.ResultsTwenty-seven (69%) biopsies of the 39 included samples were from patients with NSTIs. Microscopic bullae (p = 0.043), severe fascial inflammation (p < 0.001) and fascial necrosis (p < 0.001) were significantly more often present in the NSTI group compared to the non-NSTI group. Muscle edema (n = 5), severe muscle inflammation (n = 5), muscle necrosis (n = 8), thrombosis (n = 10) and vasculitis (n = 5) were most frequently only seen in the NSTI group. In thirteen tissues samples, there were some discrepancies between the severity of findings in the frozen section and the FFPE samples. None of these discrepancies resulted in a different diagnosis or treatment strategy.ConclusionMicroscopic bullae, severe fascial or muscle inflammation, fascial or muscle necrosis, muscle edema, thrombosis and vasculitis upon histopathological evaluation all indicate a high probability of a NSTI. At our institution, diagnosing NSTIs is aided by using intra-operative frozen section as part of triple diagnostics in ambivalent cases. Based on the relation between histopathologic findings and final presence of NSTI, we recommend frozen section for diagnosing NSTIs in ambivalent cases.

4C3 Human Monoclonal Antibody: A Proof of Concept for Non-pathogenic Proteinase 3 Anti-neutrophil Cytoplasmic Antibodies in Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a severe autoimmune vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) mainly targeting proteinase 3 (PR3), a neutrophilic serine proteinase. PR3-ANCA binding to membrane-bound PR3 on neutrophils induce their auto-immune activation responsible for vascular lesions. However, the correlation between PR3-ANCA level and disease activity remains inconsistent, suggesting the existence of non-pathogenic PR3-ANCA. In order to prove their existence, we immortalized B lymphocytes from blood samples of GPA patients in remission having persistent PR3-ANCA to isolate non-activating PR3-ANCA. We obtained for the first time a non-activating human IgG1κ anti-PR3 monoclonal antibody (mAb) named 4C3. This new mAb binds soluble PR3 with a high affinity and membrane-bound PR3 on an epitope close to the PR3 hydrophobic patch and in the vicinity of the active site. 4C3 is able to bind FcγRIIA and FcγRIIIB and has a G2F glycosylation profile on asparagine 297. 4C3 did not induce activation of neutrophils and could inhibit human polyclonal PR3-ANCA-induced activation suggesting that 4C3 is non-pathogenic. This characteristic relies on the recognized epitope on PR3 rather than to the Fc portion properties. The existence of non-pathogenic PR3-ANCA, which do not activate neutrophils, could explain the persistence of high PR3-ANCA levels in some GPA patients in remission and why PR3-ANCA would not predict relapse. Finally, these results offer promising perspectives particularly regarding the understanding of PR3-ANCA pathogenicity and the development of new diagnostic and therapeutic strategies in GPA.

PEXIVAS: The End of Plasmapheresis for ANCA-Associated Vasculitis?

Kidney involvement in ANCA-associated vasculitis is common (64%–85%) and associated with high morbidity and mortality. Despite recent advances in therapy, a significant number of patients still progress to kidney failure or death. As such, therapies that improve kidney outcomes have been pursued

The role of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis

Plasma exchange (PLEX) in addition to standard immunosuppressive treatment in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AVV) remains controversial. The aim of this study is to evaluate the effect of PLEX on AVV outcomes. Literature search was performed using Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov databases, and Google Scholar. The statistical meta-analysis and leave-one-out analysis were conducted using the Review Manager 5.3 and Open Meta-Analyst software, respectively. Ten studies were included in the meta-analysis comprising 1235 patients; 633 received conventional treatment and 602 were treated with PLEX in conjunction with induction therapy. PLEX was not associated with lower rates of either mortality at 3 (RR: 0.79, 95% CI: 0.19-3.25) and 12 months (RR: 0.73, 95% CI: 0.40-1.34) or ESRD at 3 (RR: 0.30, 95% CI: 0.30-2.42) and 12 months (RR: 1.32, 95% CI: 0.53-3.25). Similarly, no differences were captured concerning disease relapses (RR: 0.92, 95% CI: 0.62-1.36), the incidence of infections (RR: 1.05, 95% CI: 0.63-1.76), and severe adverse effects (RR: 1.04, 95% CI: 0.59-1.81). Time-to-event analysis revealed lower incidence of ESRD (HR: 0.71, 95% CI: 0.55-0.92) among patients who received PLEX, while the overall mortality was similar (HR: 0.96, 95% CI: 0.72-1.29) between the two groups. The present meta-analysis does not support the wide use of PLEX for the management of AAV in routine clinical practice. Future well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX. Key Points • PLEX is not widely recommended for the management of ANCA-associated vasculitis. • PLEX performance may reduce the overall incidence of ESRD in severe ANCA-associated vasculitis. • Well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX on AAV-related outcome.

Atypical presentation of eosinophilic granulomatosis - typical presentation in an ageing population?

Severe systemic vasculitis presenting in an 80 year old female involving a presentation with recurrent pyrexia, eosinophilia, mononeuritis multiplex against a background of late onset asthma, consistent with eosinophilic vasculitis with angiitis is described. Despite appropriate management with resolution of systemic symptoms, she failed to return to baseline functionality. Systemic vasculitis is rare in this population cohort, but it is important to consider as it is treatable albeit with a guarded outlook for full neurological recovery.

SKIN AND ORAL MOUTH ULCERS IN GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S GRANULOMATOSIS)

Granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis, is a potentially fatal systemic auto-immune disease, and it mainly affects small- and medium-sized blood vessels. It is characterized by necrotizing granulomatous lesions of the respiratory tract, vasculitis, and glomerulonephritis, and it could develop in various organs, especially the ear, nose and throat, lungs, and kidneys. In addition, 50% of cases show orbital involvement. This study presents a rare case of Wegener’s granulomatosis. A 62-year-old male had a complaint of thrush in both tongue margins and also had ocular lesions and involvement of the feet and hands. Due to the extensive ulcers we did an incisional biopsy, which revealed severe vasculitis and inflammatory infiltrate compatible with Wegener’s disease. Thereafter, we prescribed mouthwashing with benzydamine and a systemic corticosteroid. The treatment caused the lesions to disappear completely. Granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis, is a potentially fatal systemic auto-immune disease, and it mainly affects small- and medium-sized blood vessels. It is characterized by necrotizing granulomatous lesions of the respiratory tract, vasculitis, and glomerulonephritis, and it could develop in various organs, especially the ear, nose and throat, lungs, and kidneys. In addition, 50% of cases show orbital involvement. This study presents a rare case of Wegener’s granulomatosis. A 62-year-old male had a complaint of thrush in both tongue margins and also had ocular lesions and involvement of the feet and hands. Due to the extensive ulcers we did an incisional biopsy, which revealed severe vasculitis and inflammatory infiltrate compatible with Wegener’s disease. Thereafter, we prescribed mouthwashing with benzydamine and a systemic corticosteroid. The treatment caused the lesions to disappear completely.

The Points of Action of Drugs for Treating COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has reached a pandemic level. Very recently, I reported a significantly higher prevalence of diabetes and hypertension in severe COVID-19 as compared with non-severe COVID-19 by the meta-analysis. Considering that both diabetes and hypertension are risk factors for atherosclerosis, I further studied the prevalence of cardiovascular disease (CVD) in COVID-19 and found a significantly higher prevalence of CVD in severe patients than in non-severe patients. I speculate that the pre-existing vascular damage is associated with severity of COVID-19. A recent study showed that obese patients with COVID-19, despite their younger age, required more frequently assisted ventilation and access to intensive care units than normal weight patients. I thought that if the reason that COVID-19 is likely to become severe in obese people could be elucidated, the mechanism for aggravation of COVID-19 would be understood. As a result of considering a model of aggravation in obese people, I came up with the notion that pre-existing risk factors in obese people such as their vascular high-affinity for SARS-CoV-2, pro-inflammatory and pro-coagulant state and endothelial dysfunction may be likely to induce the development of “systemic severe coagulopathic vasculitis (SSCV)” in obese people. I believe that SSCV may largely contribute to the development of severe COVID-19. Here, I will describe the points of action of drugs for treating COVID-19 by using the SSCV model. J Endocrinol Metab. 2020;10(3-4):57-59 doi: https://doi.org/10.14740/jem659

Antineutrophil Cytoplasmic Antibodies and Organ-Specific Manifestations in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a rare and often severe systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). EGPA can affect multiple organ systems, but the relationships between ANCA status and the organ-specific manifestations of EGPA in previous reports were inconsistent. To investigate the association of the ANCA status with organ-specific manifestations in EGPA. We performed a systematic review of studies published before March 16, 2020, in the PubMed, Embase, Web of Science, and Cochrane Library databases. The primary outcome was the association of ANCA status with organ-specific involvements of EGPA. Odds ratios (ORs) and 95% CIs were calculated using a random-effects model. A total of 24 cross-sectional studies with 2527 patients with EGPA, including 921 ANCA-positive patients and 1606 ANCA-negative patients, were included in the meta-analysis. The significant results of pooled analyses revealed that compared with patients with EGPA with negative ANCA status, patients with EGPA with positive ANCA status had higher risks of peripheral neuropathy (OR, 1.701), renal involvement (OR, 5.097), and cutaneous purpura (OR, 1.746) and lower risks of pulmonary infiltrates (OR, 0.589) and cardiac involvement (OR, 0.427). The pooled analysis also revealed no significant association of ANCA status with asthma and involvements of the central nervous system, gastrointestinal tract, or skin. This study provides more evidence that patients with EGPA may exhibit different features of disease based on their ANCA status.

Characterization of high virulent strains of equine rhinopneumonitis virus

This article presents results of screening samples collected from horses during acute outbreaks of abortion and neurological disorders recorded in 2019-2020 in Russia. The signs of disease were characterized by severe hemorrhagic vasculitis. Massive hemorrhages were observed in organs of aborted fetuses and dead horses. Equine herpesvirus type one was isolated in cell culture. Testing to identify genes encoding glycoprotein B and polymerase catalytic subunit of certain viral isolates were carried out. Virus isolated from horses with signs of encephalomyelitis from the Northwest region had a high degree of phylogenetic relationship with the strain “89c25” of equine herpesvirus type one from Japan, 1989. The same virus was found in horses with signs of rhinopneumonia from the Ural region. The virus isolated after equine abortion from the North Caucasus region had a high degree of phylogenetic relationship with the strain “IT19m10” of equine herpesvirus type one from Italy, 2019. It was established that all viral isolates belong to non-neuropathogenic genotype - A2254.

New therapeutic strategies in lung vasculitis.

To summarize the latest publications and provide a practical overview of treatment strategies for lung vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). In patients with severe ANCA-associated vasculitis, plasma exchange, as adjunctive therapy to standard treatment, is not associated with improved survival or reduced risk of end-stage kidney disease. A regimen with reduced dose of glucocorticoids is equally effective to induce remission as a standard regimen. In patients without organ or life-threatening disease, mycophenolate mofetil can be used in combination with oral glucocorticoid therapy to induce remission, however, with a higher risk of relapse than when using rituximab or cyclophosphamide. For maintenance of remission, a tailored regimen of rituximab infusion was equivalent to a fixed regimen, with fewer perfusions. Belimumab, a human IgG1(Equation is included in full-text article.)monoclonal antibody against B-lymphocyte stimulator, did not decrease the relapse rate when added to azathioprine and glucocorticoids. Avacopan, a complement C5a receptor inhibitor, was effective in replacing high-dose glucocorticoids in achieving complete remission of vasculitis. Significant advances have been made in the treatment strategy to both induce remission and maintain remission in patients with ANCA-associated vasculitis. The choice should take into consideration efficacy, cost-effectiveness, safety profile, ease of use, and possibility of individual tailoring of treatment.

Gastrointestinal involvement in childhood vasculitides.

The aim of this narrative review was to provide a comprehensive summary of the characteristics of gastrointestinal (GI) involvement in the most common paediatric primary vasculitides. We used PubMed to primarily identify papers, reviews, case series and editorials published in English from 2000 until 31 January 2020. Based on this, we report the prevalence, clinical manifestations, diagnostic approaches and management of GI involvement in each vasculitis. Vasculitides are inflammatory blood vessel diseases, and the majority can affect the GI system with vascular, GI tract or solid organ involvement. GI involvement can sometimes complicate and delay the correct diagnosis. Clinical findings are usually nonspecific symptoms, such as fever, abdominal pain, nausea, vomiting and diarrhoea. Bleeding should alert paediatricians to the possibility of severe complicated vasculitis. Diagnosis relies mostly on imaging. If it goes unrecognised, GI involvement in paediatric vasculitis is a serious cause of morbidity and even mortality, related to bowel ischaemia and perforation. Treatment of GI symptoms depends on the type of vasculitis and usually involves high-dose steroids and immunosuppressants. GI manifestations in the most common paediatric primary vasculitides were usually nonspecific, diagnosis mostly relied on imaging, and treatment usually involved high-dose corticosteroids and immunosuppressants.