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      Kokain-induzierte Vaskulitiden und Vaskulitis-Mimics Translated title: Cocaine-induced vasculitis and mimics of vasculitis

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          Abstract

          Kokain ist ein psychoaktives Tropanalkaloid, das typischerweise in Form von Pulver nasal konsumiert wird. Das in Deutschland im Umlauf befindliche Kokain ist häufig mit Levamisol, einem Anthelminthikum mit immunmodulatorischer Wirkung, versetzt. Sowohl Kokain als auch Levamisol werden mit der Entwicklung von klinisch bedeutsamen Autoimmunphänomenen in Verbindung gebracht. Bei den sog. „cocaine-induced midline destructive lesions“ handelt es sich um Gewebedestruktionen des HNO-Traktes, die eine lokalisierte Granulomatose mit Polyangiitis imitieren können. Zusätzlich wurde auch die Entwicklung einer systemischen Vaskulitis durch Kokain und Levamisol beschrieben. Die Unterscheidung dieser Syndrome von einer primären Vaskulitis stellt häufig eine klinische Herausforderung dar, da immunserologisch in den meisten Fällen antineutrophile zytoplasmatische Antikörper (ANCA) nachweisbar sind. Die klinische Besserung ist eng mit der Beendigung des Substanzkonsums verknüpft, deshalb kommt der frühzeitigen Diagnosestellung eine besondere Bedeutung zu.

          Translated abstract

          Cocaine is a psychotropic tropane alkaloid and stimulant drug. Nasal insufflation of cocaine powder is a common route of administration. In Germany, cocaine is frequently adulterated with levamisole, an anthelminthic drug with immunomodulatory effects. Both substances are linked to various autoimmune conditions. Cocaine-induced midline destructive lesions cause a progressive destruction of osteocartilaginous structures within the upper respiratory tract and can mimic localized granulomatosis with polyangiitis. In addition, systemic vasculitis due to cocaine and levamisole has been reported. Differentiation of these conditions from primary vasculitis can be challenging because antineutrophil cytoplasmic antibodies (ANCA) are commonly detected. Early diagnosis of these conditions is crucial as clinical improvement is closely related to drug cessation.

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          Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis

          In this Consensus Statement, a group of experts propose that high-quality immunoassays, rather than indirect immunofluorescence, should be used as the primary screening method for detecting anti-neutrophil cytoplasmic antibodies when diagnosing patients with suspected granulomatosis with polyangiitis or microscopic polyangiitis.
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            Cardiovascular complications of cocaine use.

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              Neutrophil Extracellular Traps in ANCA-Associated Vasculitis

              A group of pauci-immune vasculitides, characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of antineutrophil cytoplasmic antibodies (ANCAs), is referred to as ANCA-associated vasculitis (AAV). ANCAs against proteinase 3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) are found in over 90% of patients with active disease, and these ANCAs are implicated in the pathogenesis of AAV. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally, it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. AAV patients also possess elevated levels of NETs in the circulation. ANCAs are capable of inducing NETosis in neutrophils, and their potential to do so has been shown to be affinity dependent and to correlate with disease activity. Neutrophils from AAV patients are also more prone to release NETs spontaneously than neutrophils from healthy blood donors. NETs contain proinflammatory proteins and are thought to contribute to vessel inflammation directly by damaging endothelial cells and by activating the complement system and indirectly by acting as a link between the innate and adaptive immune system through the generation of PR3- and MPO-ANCA. Injection of NET-loaded myeloid dendritic cells into mice results in circulating PR3- and MPO-ANCA and the development of AAV-like disease. NETs have also been shown to be essential in a rodent model of drug-induced vasculitis. NETs induced by propylthiouracil could not be degraded by DNaseI, implying that disordered NETs might be important for the generation of ANCAs. NET degradation was also highlighted in another study showing that AAV patients have reduced DNaseI activity resulting in less NET degradation. With this in mind, it might be that prolonged exposure to proteins in the NETs due to the overproduction of NETs and/or reduced clearance of NETs is important in AAV. However, not all ANCAs are pathogenic and some might possibly also aid in the clearance of NETs. A dual role for ANCAs in relation to circulating NET levels has been proposed because a negative correlation was observed between PR3-ANCA and NET remnants in patients in remission.
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                Author and article information

                Contributors
                n.ruffer@uke.de
                Journal
                Z Rheumatol
                Z Rheumatol
                Zeitschrift Fur Rheumatologie
                Springer Medizin (Heidelberg )
                0340-1855
                1435-1250
                25 May 2022
                25 May 2022
                2023
                : 82
                : 7
                : 606-614
                Affiliations
                [1 ]Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Bad Bramstedt, Deutschland
                [2 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Sektion Rheumatologie und entzündliche Systemerkrankungen, III. Medizinische Klinik und Poliklinik, , Universitätsklinikum Hamburg-Eppendorf, ; Martinistr. 52, 20246 Hamburg, Deutschland
                [3 ]GRID grid.490302.c, Konsultations- und Referenzzentrum für Vaskulitis-Diagnostik, Pathologie-Hamburg, , Labor Lademannbogen MVZ GmbH, ; Hamburg, Deutschland
                [4 ]GRID grid.411656.1, ISNI 0000 0004 0479 0855, Universitätsklinik für Rheumatologie, Immunologie und Allergologie, Inselspital, , Universitätsspital Bern, ; Bern, Schweiz
                Author notes
                [Redaktion]

                Ulf Müller-Ladner, Bad Nauheim

                Uwe Lange, Bad Nauheim

                Author information
                http://orcid.org/0000-0001-8394-969X
                Article
                1217
                10.1007/s00393-022-01217-1
                10495486
                35612660
                82616b71-8e71-4fdf-8009-dd662cccb00e
                © The Author(s) 2022

                Open Access Dieser Artikel wird unter der Creative Commons Namensnennung 4.0 International Lizenz veröffentlicht, welche die Nutzung, Vervielfältigung, Bearbeitung, Verbreitung und Wiedergabe in jeglichem Medium und Format erlaubt, sofern Sie den/die ursprünglichen Autor(en) und die Quelle ordnungsgemäß nennen, einen Link zur Creative Commons Lizenz beifügen und angeben, ob Änderungen vorgenommen wurden.

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                History
                : 2 April 2022
                Funding
                Funded by: Universitätsklinikum Hamburg-Eppendorf (UKE) (5411)
                Categories
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                Custom metadata
                © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2023

                Rheumatology
                cocaine-induced midline destructive lesions,levamisol,granulomatose mit polyangiitis,anca,mimics,levamisole,granulomatosis with polyangiitis

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