Meningeal involvement in Wegener's granulomatosis (WG) is rare and only 32 cases have been reported by Reinhold‐Keller and coworkers.1,2 The outcome of the disease has improved with the institution of cytotoxic agents.3 We report on a patient with WG and progressive pachymeningeosis despite treatment with cyclophosphamide (CyC) and glucocorticoids who responded well to infliximab treatment.
In December 2003 a 34 year old male chemist was diagnosed with localised WG, according to the American College of Rheumatology criteria and the Capel Hill Conference criteria, on the basis of granulomatous nasal inflammation, left‐sided otitis media, and the detection of proteinase‐3‐antineutrophilic cytoplasmic antibodies (PR3‐ANCA) >100 U/ml (normal <5 U/ml).4,5 Because of progressive hearing loss oral prednisolone (1 mg/kg body wt) and intravenous CyC 0.8 g/m2/month were started.
After 3 months when prednisolone was tapered to 15 mg/day the patient developed headache, bilateral paresis of the abducens nerve, and paresis of the left oculomotor nerve. Magnetic resonance imaging (MRI) disclosed dural thickening with enhanced gadolinium uptake across both cerebral hemispheres and the basal region (fig 1A), and another increase of PR3‐ANCA (46 U/ml) supported the suspicion that WG had spread to the meninges and had become generalised. Methylprednisolone pulse therapy and oral CyC (2 mg/kg body wt) were successfully started.
Figure 1 (A) T1 weighted axial MR scan of a 43 year old male patient after contrast application shows meningeal inflammatory involvement with 3 mm thickening of the left hemispherical and right frontal meninges (arrows). (B) Six months after treatment with infliximab (5 mg/kg body wt) at weeks 0, 2, 6 and 8‐weekly thereafter, meningeal contrast enhancement and thickening had clearly regressed.
After prednisolone was tapered to 50 mg/day the patient again complained of headache and incapacitating bilateral diplopia. MRI findings had remained virtually unchanged; the modified Birmingham Vasculitis Activity Score (BVAS/WG)6 was 9 (BVAS1 = 4; BVAS2 = 5), and the PR3‐ANCA level 18 U/ml.
Because oral CyC and prednisolone could not control the disease this led us to examine reports that infliximab might be effective in treating refractory WG.7 After written informed consent was obtained and no signs of infection were found, infliximab (5 mg/kg body wt) at weeks 0, 2, and 6, and thereafter at 8‐weekly intervals was started. After 2 weeks clinical symptoms of cerebral involvement had subsided, the BVAS/WG had fallen to 4, and the PR3‐ANCA level was 10 U/ml. Oral CyC was reduced to 1 mg/kg body wt and prednisolone to 5 mg/day within 3 months. Over the following 12 months, the patient remained free of clinical symptoms and MRI findings improved impressively (fig 1B), indicating that infliximab was effective in controlling meningeal involvement.
Granuloma formation is a hallmark in localised WG. These granulomas consist predominantly of tumour necrosis factor α (TNFα) expressing T cells and macrophages, and different groups have shown that infliximab, a TNFα neutralising agent, was effective in refractory WG.7,8 Our patient originally presented with localised WG that generalised and spread to the meninges despite immunosuppressive treatment. Infliximab induced and maintained remission in our patient with no side effects reported to date. This shows a difference between infliximab and etanercept, which could not prevent relapses in a recently published placebo‐controlled trial.9
To our knowledge, ours is the first report demonstrating that infliximab may be a viable treatment option in generalised WG not responding to oral CyC and glucocorticoids.
References
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