Meningeal involvement in apparently ANCA-negative Wegener's granulomatosis: a role for PR3 capture-ELISA?

SIR, Central nervous system (CNS) involvement is rare in Wegener's granulomatosis (WG): the spectrum of CNS manifestations includes cerebrovascular events, seizures and cranial nerve abnormalities [1, 2]. Meningitis is exceedingly rare, and its diagnosis often challenging [1–3]. A 57-yr-old man was admitted to hospital because of untreatable headache, photophobia, neck stiffness and paranasal sinus pain. Eight years earlier. WG had been diagnosed because of inflammatory involvement of the upper (sinusitis, anosmia) and lower (pulmonary nodules, histologically showing granulomas with giant cells and necrotizing vasculitis) respiratory tract, associated with high ESR and cytoplasmic-ANCA (C-ANCA), which were anti-proteinase 3 (PR3) (103 EU/ml, normal <20) by routine ELISA. Cyclophosphamide (CYC) and prednisolone (PDN) therapy was successfully conducted for 2 years. On admission, ESR (75 mm/Ih) and CRP (116 mg/l; normal <5) were high. ANCAs tested negative using indirect immuno-fluorescence (IIF) (ZenTech, Angleur, Belgium) and antigen-specific, direct-ELISA for PR3 and myeloperoxidase (Fenning BioMed GmbH, Germany). Head CT showed mucosal thickening of the maxillary sinuses and turbinates without bone erosions. Brain MRI disclosed dural thickening, particularly of the tentorium cerebelli and the posterior portion of the falx; these sites showed pronounced contrast-enhancement (Fig. 1A and D). Moderate dural thickening and enhancement were also observed along the petrous bone and the cavernous sinuses. The meninges adjacent to the orbital, nasal and paranasal areas were normal. Cerebrospinal fluid (CSF) analysis revealed pleocytosis (WBC count 32/mm 3 , predominantly lymphocytes), but normal protein and glucose levels; CSF cultures were negative for viruses, bacteria and fungi. CSF cytology was unremarkable. Part of the patient's serum obtained on admission had been stored at À808C, thus we used it to recheck ANCAs using PR3-capture ELISA (Phadia, Freiburg, Germany), which, unlike the routine assay, showed strongly positive PR3-ANCAs (121 AU/ml, normal <7). CSF analysis by routine techniques and capture-ELISA was negative for ANCA. Chest CT ruled out lung involvement. A WG relapse with upper airway tract and meningeal involvement was thus diagnosed, and PDN (1 mg/kg/day) plus CYC (1.5 mg/kg/day) therapy was started. The cranial symptoms resolved within 10 days, and MRI also revealed a reduction in meningeal thickening and contrast-enhancement (Fig. 1B and E). The treatment was continued for a 12-month period, at the end of which the meningeal abnormalities disappeared (Fig. 1C and F). The frequency of meningitis ranges between 0% and 7% of WG cases [1, 2]. WG-related meningitis can result from cerebral vessel vasculitis, direct invasion from adjacent …