Auto-Immunity and Systemic Vasculitis

: Viruses can induce autoimmune diseases, in addition to genetic predisposition and environmental factors. Particularly, coronaviruses are mentioned among the viruses implicated in autoimmunity. Today, the world's greatest threat derives from the pandemic of a new human coronavirus, called “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), the responsible agent of coronavirus disease 2019 (COVID-19). COVID-19 originated in Wuhan, the capital of Hubei, China in December 2019 and, to date, has spread to at least 187 countries. This review focuses on autoimmune manifestations described during COVID-19, including pro-thrombothic state associated to antiphospholipid antibodies (aPL), acute interstitial pneumonia, macrophage activation syndrome, lymphocytopenia, systemic vasculitis, and autoimmune skin lesions. This offers the opportunity to highlight the pathogenetic mechanisms common to COVID19 and several autoimmune diseases, in order to identify new therapeutic targets. In a supposed preliminary pathogenetic model, SARS-CoV-2 plays a direct role in triggering widespread microthrombosis and microvascular inflammation, because it is able to induce transient aPL, endothelial damage and complement activation at the same time. Hence, endothelium might represent the common pathway in which autoimmunity and infection converge. In addition, autoimmune phenomena in COVID-19 can be explained by regulatory T cells impairment and cytokines cascade.

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AB0521 COST OF ILLNESS OF ANCA-ASSOCIATED VASCULITIS IN ITALY: DATA LINKAGE ANALYSIS OF MULTIPLE CLINICAL AND ADMINISTRATIVE DATABASES IN THE PROVINCE OF UDINE, ITALY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2585 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1558.1-1558

Author(s):

L. Quartuccio ◽

E. Treppo ◽

S. De Vita ◽

F. Valent

Keyword(s):

Health Care ◽

Cost Of Illness ◽

Systemic Vasculitis ◽

Health Information System ◽

Clinical Manifestations ◽

Administrative Databases ◽

Rank Test ◽

Hospital Discharges ◽

Severe Infections ◽

Regional Population

Background:ANCA-associated vasculitides (AAV) are a group of systemic vasculitis carrying a high risk of hospitalization because the multiorgan involvement, the acute nature of some clinical manifestations, the chronic but very disabling course of some other manifestations and finally the risk of severe infections due to chronic glucocorticoid and immunosuppressor administration. However, data on cost of illness due to AAV are lacking.Objectives:to estimate the cost of illness in patients suffering from AAV in the province of Udine (about 500,000 inhabitants), Friuli Venezia Giulia (FVG), Italy, from year 2010 to 2018.Methods:integration of the information coming from many administrative databases were used to this end. The Regional Health Information System of FVG was used as the source of information for this retrospective cohort study. The system covers the entire regional population and includes various electronic health administrative databases that can be linked with one another on an individual basis through a unique encrypted identifier. In particular, the following databases were matched: the database of the health care beneficiaries (including demographic information and the residential history of all of the subjects living in FVG), the hospital discharge database, the database of exemptions from medical charges, the database of the laboratories. The population under study was selected based on the following inclusion criteria: patients were residents in the province of Udine and they had to carry the exemption code for AAV, including GPA, or EGPA, or MPA. This population was observed from 2010 to 2018.Results:57 patients (201 patient-years) with AAV were identified. They were ANCA-positive in 44/57 (77%). GPA, EGPA and MPA was diagnosed in 18 (31,6%), 15 (26,3%), 11 (19,3%) patients, respectively. The mean age at diagnosis was 54,5 (17,5) years. The disease itself was the main cause of hospitalization in almost half of the hospital discharges (60/126, 47,6%). Four patients died during the observation period due to vasculitis itself (1), pneumonia (2), or haematological malignancy (1). Time to the first event (death or hospitalization) was significantly higher in ANCA-negative AAV patients than in ANCA-positive AAV patients (p=0,03, Log-Rank test), ANCA-positive AAV patients having a three-times higher risk (HR 3,38 95%CI 1,13-10,08, p=0,03). Total estimated cost was € 1,215,078, corresponding to € 6,168 patient-year. Costs for ANCA-positive AAV patients were much higher than those for ANCA-negative AAV patients (€ 1,115,253 vs € 99,825, and € 7058 per person-year vs € 2,559 per person-year, respectively). GPA and MPA showed the highest costs if compared to EGPA [GPA: € 239,168 (€ 5199 per person-year) vs MPA: € 281,502 (€ 4771 per person-year) vs EGPA: € 214,287 (2329 per person-year), respectively]. Costs for hospitalization were the highest [€ 734,957 (€ 3731 per person-year) vs other costs € 480,121 (€ 2437 per person-year)].Conclusion:costs for AAV are very high, confirming the high health care burden of this illness. Management of ANCA-positive patients rather than ANCA-negative patients was burdened by the highest costs. GPA and MPA showed the highest direct costs for hospitalization, which very frequently occurred due to the vasculitis itself.Disclosure of Interests:Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Francesca Valent: None declared

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AB0463 ETIOLOGY OF PALPABLE PURPURA; A SINGLE CENTER EXPERIENCE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5471 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1530.1-1530

Author(s):

G. Kaynar ◽

O. C. İçaçan ◽

S. Çelik ◽

M. Yalçin Mutlu ◽

C. Bes

Keyword(s):

Drug Use ◽

Histopathological Examination ◽

Leukocytoclastic Vasculitis ◽

Systemic Vasculitis ◽

Skin Lesions ◽

Serological Tests ◽

Recent Infection ◽

Important Place ◽

Palpable Purpura ◽

Underlying Diseases

Background:Purpura are lesions that occur after bleeding on the skin, mucous or serosal surfaces. Purpura can be classified into 2 subgroups; which are linked to thrombocytopenia and non-trombocytopenic purpura. While thrombocytopenic purpura often occurs due to a hematological disease; in non-trombocytopenic purpura etiological causes are very variable, and systemic vasculitis has an important place among them.Objectives:The demographic features of the patients applying with purpura and the underlying causes and diseases were aimed to be revealed.Methods:44 consecutive patients (22 women, 22 men) who were admitted to the hospital in the last 6 months, due to purpura were evaluated. Average age of patients was 49.6 ± 19.6 years. Patients were questioned about a recent infection, drug use, concomitant or underlying diseases. The serological tests and other laboratory tests for etiology were performed and biopsy was taken from the skin lesions which are appropriate.Results:While 4 (9%) patients had widespread purpura on the trunk-upper-lower extremities, in 22 (50%) patients purpuric lesions were limited only to the lower limb. The period between the onset of the first symptom and the admission to the hospital was longer than 4 weeks in 35 (79.5%) patients, and shorter than 1 week in 9 (20.5%) patients. 24 (54%) patients had an anamnesis of infection 2-3 weeks before purpura, and 20 (45%) patients had an anamnesis of drug use. The most common accompanying symptom was abdominal pain and was present in 15 (34%) patients. Biopsy was performed from the skin lesion in 37 patients. Histopathological examination of all was compatible with leukocytoclastic vasculitis. In indirect immunofluorescence staining, 17 were found to be IgA positive. 2 (4.5%) patients were diagnosed PR3-ANCA positive granulomatosis with polyangiitis. 1 patient had Hepatitis B virus infection was detected in 1 patient (2.2%), HIV infection was detected in 1 patient (2.2%) and malignancy was detected in 1 patient (2.2%).Conclusion:In our study, the most common reason was found as IgA vasculitis in patients presenting with palpable purpura. Although vasculitic involvement was limited to the skin in most patients, organ-threatening systemic vasculitis was detected in a few patients. Patients applying with Purpura should be questioned for infection and drug use, should be examined for underlying diseases including systemic vasculitis, and closely monitored for organ involvement.Disclosure of Interests:None declared

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Atypical Bacterial Pathogens and Small-Vessel Leukocytoclastic Vasculitis of the Skin in Children: Systematic Literature Review

Pathogens ◽

10.3390/pathogens10010031 ◽

2021 ◽

Vol 10 (1) ◽

pp. 31

Author(s):

Céline Betti ◽

Pietro Camozzi ◽

Viola Gennaro ◽

Mario G. Bianchetti ◽

Martin Scoglio ◽

...

Keyword(s):

Mycoplasma Pneumoniae ◽

Legionella Pneumophila ◽

Leukocytoclastic Vasculitis ◽

Systemic Vasculitis ◽

Bacterial Pathogen ◽

Small Vessel ◽

Small Vessel Vasculitis ◽

Systemic Involvement ◽

Symptomatic Disease ◽

Atypical Pathogen

Leukocytoclastic small-vessel vasculitis of the skin (with or without systemic involvement) is often preceded by infections such as common cold, tonsillopharyngitis, or otitis media. Our purpose was to document pediatric (≤18 years) cases preceded by a symptomatic disease caused by an atypical bacterial pathogen. We performed a literature search following the Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines. We retained 19 reports including 22 cases (13 females and 9 males, 1.0 to 17, median 6.3 years of age) associated with a Mycoplasma pneumoniae infection. We did not find any case linked to Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella pneumophila. Patients with a systemic vasculitis (N = 14) and with a skin-limited (N = 8) vasculitis did not significantly differ with respect to gender and age. The time to recovery was ≤12 weeks in all patients with this information. In conclusion, a cutaneous small-vessel vasculitis with or without systemic involvement may occur in childhood after an infection caused by the atypical bacterial pathogen Mycoplasma pneumoniae. The clinical picture and the course of cases preceded by recognized triggers and by this atypical pathogen are indistinguishable.

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THU0597 CORNEAL MELT - DON’T ALWAYS BLAME RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2643 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 540.3-540

Author(s):

A. Munir ◽

C. Sheehy

Keyword(s):

Rheumatoid Arthritis ◽

Renal Biopsy ◽

Systemic Vasculitis ◽

Lower Lobe ◽

Visual Outcome ◽

Eye Drops ◽

Poor Visual Outcome ◽

Methyl Prednisolone ◽

History Of ◽

And Function

Background:Corneal melt is a rare inflammatory disease of the peripheral cornea; it may lead to perforation of the globe and visual failure. Corneal melt can be a manifestation of systemic vasculitis in patients with RA and other conditions, such as cancer. Without early and aggressive treatment it may be associated with a poor visual outcome and a high mortality. It has been reported in patients with stable RA.Objectives:A case report in a patient with long standing but well controlled Rheumatoid Arthritis (RA) and metastatic disease.Methods:A 75 year old male with a background of sero positive Rheumatoid Arthritis for more than 10 years presented to the Eye Casualty with a two week history of a painful left red eye. His other medical history was significant for Stage IIB poorly differentiated cancer of the left lower lobe. Left lower lobectomy with a patch of diaphragm resected. Intratumoural lymphovascular invasion noted. He completed Adjuvant Carboplatin/Vinorelbine chemotherapy September, 2017. He had DVT proximal left leg 22ndof September, 2017. Follow up CT in 2018 demonstrated a right renal upper pole lesion for which he was awaiting biopsy with?metastatic lung disease vs primary renal carcinoma. His RA was well controlled on Methotrexate 10mg weekly. He had been treated by the ophthalmology team for left marginal Keratitis for the prior 2 months with steroid eye drops without significant improvement. On presentation to ED, he described sharp eye pain, waking him from the sleep, associated with watery discharge and photophobia. Examination showed corneal melt in left eye involving 25% of inferior portion of the cornea and spastic entropion with injecting eye lashes. He had no active joints and there were no other signs of vasculitis. CRP was 4.1. He had a negative ANA and ANCA; viral swabs were negative. He was admitted under the medical team. Intravenous Methyl Prednisolone was started. The patient felt better after 5 days of Methyl Prednisolone. Left temporary tarsorrhaphy was done by Ophthalmology. Cyclophosphamide was initiated after discussion with Oncologist pending the result of the renal biopsy. Patient was discharged after 5 days of admission in the hospitalResults:The renal biopsy was positive for metastatic Squamous cell carcinoma of lung. Cyclophosphamide was withdrawn and he was started on Carboplatin/Gemcitabine. The corneal melt improved with complete resolution of his visual symptoms.Conclusion:In this case, although the history of RA was felt by the ophthalmology team to be the most likely association with the corneal melt, we would argue the oncological diagnoses were likely the driving force behind the presentation.References:[1]Sule A, Balakrishnan C, Gaitonde S, Mittal G, Pathan E, Gokhale NS, et al. Rheumatoid corneal melt. Rheumatology (Oxford)2002;41:705–6.[2]S. Yano, K. Kondo, M. Yamaguchi et al., “Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition,” Anticancer Research, vol. 23, no. 5, pp. 3639–3650, 2003.Disclosure of Interests:None declared

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Stereotactic Radiotherapy in the Treatment of Paraneoplastic Vasculitis in Oligometastatic Renal Cell Carcinoma

Current Oncology ◽

10.3390/curroncol28030162 ◽

2021 ◽

Vol 28 (3) ◽

pp. 1744-1750

Author(s):

Laura Burgess ◽

Marissa Keenan ◽

Alan Liang Zhou ◽

Kiefer Lypka ◽

Delvina Hasimja Saraqini ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Stereotactic Radiotherapy ◽

Renal Cell ◽

Systemic Vasculitis ◽

Primary Lesion ◽

Paraneoplastic Syndromes ◽

Healthy Male ◽

Palpable Purpura ◽

First Case

Approximately 20% of renal cell carcinoma (RCC) is diagnosed because of paraneoplastic manifestations. RCC has been associated with a large variety of paraneoplastic syndromes (PNS), but it is rarely associated with PNS vasculitis. We present a case of a previously healthy male who presented with systemic vasculitis; bitemporal headaches, diplopia, polyarthritis, palpable purpura, tongue lesion, peri-orbital edema, scleritis, chondritis and constitutional symptoms. He was subsequently found to have oligometastatic RCC. Both his primary lesion and site of oligometastasis were treated with stereotactic radiotherapy (SBRT) and resulted in the resolution of his vasculitis, as well as sustained oncologic response. This is the first case to demonstrate that effective sustained treatment for PNS vasculitis due to oligometastatic RCC is possible with SBRT.

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Vasculitis: From Target Molecules to Novel Therapeutic Approaches

Biomedicines ◽

10.3390/biomedicines9070757 ◽

2021 ◽

Vol 9 (7) ◽

pp. 757

Author(s):

Sang-Wan Chung

Keyword(s):

Systemic Vasculitis ◽

Alkylating Agents ◽

Large Vessel Vasculitis ◽

Large Vessel ◽

Biologic Therapies ◽

Therapeutic Approaches ◽

Novel Treatments ◽

Treatment Regimens ◽

Immune Mediated ◽

Target Molecules

Systemic vasculitis is a group of diverse diseases characterized by immune-mediated inflammation of blood vessels. Current treatments for vasculitis, such as glucocorticoids and alkylating agents, are associated with significant side effects. In addition, the management of both small and large vessel vasculitis is challenging due to a lack of robust markers of disease activity. Recent research has advanced our understanding of the pathogenesis of both small and large vessel vasculitis, and this has led to the development of novel biologic therapies capable of targeting key cytokine and cellular effectors of the inflammatory cascade. It is anticipated that these novel treatments will lead to more effective and less toxic treatment regimens for patients with systemic vasculitis.

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