Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine‐induced midline destructive lesions but not autoimmune vasculitis

Abstract

Objective. Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL.Methods. HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen.Results. Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA-positive CIMDL sera were also PR3 ANCA-positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA-negative, as were sera obtained from healthy controls.Conclusion. Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.

Cutaneous vasculopathy associated with cocaine use

“…Patients with CIMDL are usually positive for pANCA that reacts with human neutrophil elastase (HNE) or, less frequently, with PR3, but none of these patients seem to react with MPO (3)(4)(5). Such specificity of anti-MPO to cutaneous vasculopathy and not CIMDL suggests (although it does not prove) a different pathogenesis of these 2 conditions, despite both of them being triggered by cocaine use.…”

“…A variety of rheumatologic manifestations have been described in association with cocaine use, including different connective tissue diseases, vasculitides (2), and cocaine-induced midline destructive lesions (CIMDL), a condition that frequently mimics granulomatosis with polyangiitis (Wegener's) (GPA) (3)(4)(5). In addition, there are reports of cocaine in association with skin vasculopathy, which usually has the clinical appearance of cutaneous vasculitis with the absence of significant vascular inflammation on biopsy (2,6).…”

S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis

“…Die kommerziell verfügbaren Tests unterscheiden sich hierin zum Teil erheblich [91]. In Verdachtsfällen kann zudem eine Testung auf ANCA gegen humane Leukozytenelastase (HLE) sinnvoll sein, da diese mit dem Gebrauch von Kokain assoziiert sind und Kokainabusus zu vaskulitisartigen Krankheitsbildern führen kann [257]. Die Testung weiterer ANCA-Subspezifitäten ist nur in Ausnahmefällen sinnvoll und spielt in der Routinediagnostik der AAV keine Rolle.…”

Case 10-2013

“…8,9 These problems generally remain confined to the upper respiratory tract and tissues of the face and are not associated with a disseminated vasculitis. Although high titers of ANCAs result, the antigen specificity is for human neutrophil elastase.…”

“…Although high titers of ANCAs result, the antigen specificity is for human neutrophil elastase. 8,9 Unfortunately, such patients also have ANCAs directed against proteinase 3, making the distinction between cocaine-induced midline lesions and granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) difficult. We are not informed of this Thus, a bacterial infection, such as those acquired from injection-drug use, is unlikely.…”