Spontaneous pneumo-mediastinum in systemic sclerosis a case report.

ment [4–6]. This prevalence is high if we consider that only 5–10% of WG patients were shown to have CNS disease in large cohorts [6]. Therefore, ANCA-negative WG may hide remarkable CNS involvement [5]. In our patient, WG initially presented as a systemic disease and C-ANCA (anti-PR3) tested positive using routine IIF and direct-ELISA. At the time WG relapsed with upper airway tract and meningeal involvement, ANCAs were negative on routine assays. Surprisingly, PR3-capture ELISA detected strongly positive PR3-ANCAs. PR3-capture ELISA uses, as a capturing ligand for PR3, a mouse monoclonal antibody (MoAb 4A3) directed to a PR3 epitope that is rarely targeted by human ANCAs. The PR3 epitopes may be more accessible using this assay, which is also thought to better preserve the conformation of PR3 [7]. In the first clinical evaluation of this capture-ELISA, its diagnostic sensitivity was higher compared with C-ANCA by IIF in patients with WG-related renal disease [7]. Recently, a multicentre evaluation of capture-ELISA compared with direct-ELISAs and IIF confirmed the higher sensitivity of capture-ELISA [8]. Moreover, detection of PR3-ANCA by capture-ELISA showed a higher sensitivity than that obtained by direct-ELISA in diagnosing relapse during the follow-up of vasculitis [9]. The superiority of PR3-capture ELISA could be due to analytical reasons or to its ability to detect PR3-ANCA/PR3 immune complexes [10]. Meningitis is a rare and insidious complication of WG and it may be difficult to distinguish from meningeal involvement secondary to neoplasms or infections, particularly in immunosuppressed patients. In such cases, finding positive PR3-ANCAs can be useful to steer the diagnosis towards a WG manifestation. This is also why a more sensitive assay, such as PR3-capture ELISA, should be included in the diagnostic armamentarium of apparently ANCA-negative WG cases, particularly when atypical clinical presentations make the diagnosis more challenging. Like in our case, if diagnosed early, WG-related meningitis usually responds to immunosuppressive therapy, whereas if left untreated it can cause severe and life-threatening complications.