Rheumatology Advance Access originally published online on May 30, 2006
Rheumatology 2006 45(8):1047-1048; doi:10.1093/rheumatology/kel172
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LETTER TO THE EDITOR |
Infliximab as rescue therapy in three cases of paediatric Wegener's granulomatosis
Nuffield Orthopaedic Centre, Oxford, UK, 1 British Columbia Children's Hospital, Vancouver, Canada and 2 Seattle Children's Hospital, Washington, USA
Correspondence to: Dr Nick Wilkinson, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX4 7LD, UK. E-mail: nick.wilkinson{at}noc.anglox.nhs.uk
SIR, This is the first report of infliximab (IFX) use in children with severe, refractory Wegener's granulomatosis (WG), a necrotizing vasculitis of the upper respiratory tract and kidneys. The rationale for tumour necrosis factor 
(TNF) blockade includes a key role of TNF in granuloma formation and maintenance of vasculitis in WG [1–6]. In addition, IFX has been shown to be effective in the management of refractory WG in three case series of adult patients [7–9].
Each of the three cases fulfilled the American College of Rheumatology (ACR) criteria for WG [10], and a standard infusion regimen of IFX was commenced in combination with methotrexate (MTX). Patients 1 and 2, males aged 11 and 12 yrs, respectively, each received 3 mg/kg IFX 1.5 yrs after the disease onset for severe active renal disease resistant to treatment with both oral and high-dose pulsed intravenous cyclophosphamide (CYC). Renal biopsy in each child demonstrated active necrotizing pauci-immune glomerulonephritis and >30% focal segmental sclerosis. Patient 3, a 16-yr-old female, received 5 mg/kg IFX shortly after diagnosis for necrotizing tracheitis, lung nodules and neurosensory hearing loss. Each patient continued to receive steroids and CYC initially, and was closely monitored for infections and other adverse events, potentially attributable to the cumulative cytotoxicity of CYC and IFX on lymphocytes. The clinical response was measured in terms of organ function, proteinase-3 (PR-3) antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and change in medication.
All patients tolerated the treatment for over 1 yr, and doses of IFX were increased to 10 mg/kg in Patients 1 and 3 because of an inadequate response. Viral upper respiratory tract infections were noted in two patients, but were of normal duration, and there were no opportunistic or other bacterial infections. There were no infusion reactions or other significant adverse events.
Marked improvement in disease activity was seen in Patient 2, who was commenced on IFX following an episode of hypertensive encephalopathy attributable to active renal vasculitis. Over the first 3 months, serum creatinine fell from 315 to 11 µmol/l, blood pressure normalized and prednisolone was weaned from 2 mg/kg/day to 0.2 mg/kg/day. The change in PR-3 antibody, ESR and CRP was from 173 IU/l, 65 mm/h, and 10.7 mg/dl at baseline, respectively, to 33 IU/l, 30 mm/h and 0.85 mg/dl by 3 months. This level of improvement was maintained and CYC was weaned off over the subsequent 9 months. Prednisolone dose at 1 yr was 0.1 mg/kg.
The other two patients had transient clinical improvements in the first 3 months after commencing IFX, but the subsequent response was equivocal. Four months after swapping Patient 1 from oral to intravenous pulsed CYC (1 mg/m2) because of gastrointestinal intolerance, IFX was commenced to control flaring of active renal disease and recurrent acute scleritis. The scleritis remitted without the need for ongoing topical steroids. The CYC was swapped for MTX (15 mg/m2 subcutaneously) 6 months later when he redeveloped gastrointestinal intolerance. There was no deterioration in disease activity, and the gastrointestinal symptoms again settled. Because of unchanged abnormal urinary sediment (10–25 red blood cells per high-power field, 0.3 g protein/24 h and occasional granular casts), steroid dose (0.25 mg/kg) and raised inflammatory markers, the IFX dose was increased to 6 mg/kg and 10 mg/kg at intervals of 4 months. A repeat renal biopsy, undertaken for insidious renal deterioration, has shown persistent active glomerulonephritis, and the IFX was stopped following the recent addition of intravenous CYC. In Patient 3, radiographic resolution of the lung nodules and improvement in hearing tests were observed, but there was progressive tracheal narrowing despite increasing IFX to 10 mg/kg. There were some sustained improvement in inflammatory markers, and steroids were weaned from 2 to 0.25 mg/kg/day. IFX was subsequently stopped and rituximab was given.
The outcome of IFX use in paediatric WG does not appear to be the same as that reported in adult series [7–9], but its role as a rescue therapy has been demonstrated in one case. Further assessment of the efficacy and safety of IFX in combination therapy is required in the form of a multicentre randomized controlled trial.
The authors have declared no conflicts of interest.
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