Chemotherapy has been used for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen, used to treat B-cell lymphoma and reportedto be effective in some neuropathies with IgM autoreactivity.
A 72-year-old man with CIDP refractory to steroids, plasma exchange, IVIg, and cyclosporin.
He was unable to walk; severe impairment was present also at the upper limbs. Electrodiagnostic studies revealed slowing of motor and sensory conduction velocities, and prolonged distal motor latencies. Immunoelectrophoresis evidence an IgM/k monoclonal gammopathy.
Antibodiesto Myelin Associated Glycoprotein (MAG) and other peripheral nerve
antigens were negative. Bone marrow biopsy documented a small lymphocytic B-cell lymphoma (CD20+). Treated with Rituximab (375 mg/m2 for 4 weeks), the patient presented at follow-up evaluations
(3, 6 and 8 months later) a progressive improvement.Eventually, he was able to walk, and regained full strength at upper limbs.
Consistently, electrical studies improved. We suggest considering treatment with Rituximab in CIDP resistant to conventional therapy, at least in cases associated with IgM
lymphoproliferative diseases. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune- mediated disease responsive to intravenous immunoglobulins (IVIg), plasma exchange or
corticosteroids. CIDP may be associated with IgM monoclonal gammopathy, with the IgMs directed towards peripheral nerve antigens. Immunosuppression is sometimes effective (Kelly et al.,
1988), but there is concern about long-term treatment (Nobile-Orazio et al., 2000). Rituximab is a chimeric monoclonal antibody against the CD20 antigen on B-cells. The B-cell depletion
and the lack of relevant side-effects have encouraged the use of rituximab also in diseases with non-malignant B-cell proliferation (Zaja et al., 2003a,b), and in neuropathy with IgM monoclonal gammopathy (Renaud
et al., 2003) or polyclonal IgM antibodies to peripheral nerve antigens (Pestronk et al., 2003).
We describe a patient with a drug-resistant CIDP, who dramatically improved after rituximab administration. A 72-year-old man came to our attention after a
3-year history of CIDP, diagnosed at the beginning of 1999 for progressive sensory loss and unsteady gait. He was treated with IVIg
with benefit, and discharged on steroids, with further improvement. He was capable of walking, riding the bike, climbing the stairs.
Steroids were gradually tapered. Following a relapse, he was started again on steroids and IVIg, with only partial improvement. Plasma exchange was considered, but soon interrupted
for the occurrence of atrial fibrillation. An IgM monoclonal gammopathy was detected. Bone marrow biopsy was not performed. In
December 1999, azathioprine was started and IVIg given. The patient kept worsening both as to muscle strength (MRC 3/5, proximally and distally), and to sensory loss. Azathioprine was withdrawn, and
cyclosporin tried with no benefit.
When he came to our attention, the patient was wheel-chair bound; upper limbs were severely impaired and he was incapable of eating without aid. Deep tendon reflexes were absent. Peroneal and sural nerves CV were not recordable; slowing of ulnar and median nerves motor CV (13 m/s, 10 m/s) with prolonged distal latency (15 ms, 10 ms), conduction block, and evidence of muscledenervation were present. Immunoelectrophoresis evidenced an IgM/k monoclonal gammopathy (total IgM 3.41 g/l). Bence-Jones proteinuria was absent. Antibodies to MAG, sulphatides and gangliosides were absent. Bone marrow biopsy evidenced low-grade-small-B-cell lymphoma (CD20+CD5-). Treated with
rituximab (375 mg/m2 for 4 weeks), the patient presented at follow-up (3, 6, 8 and 11 months later) a progressive improvement, more evident starting from 6 months after therapy. Eventually, he was able to walk unassisted for a short distance. He regained full functionality at upper limbs and was able to perform hisdaily activities (shaving, washing, eating) independently. The IgM/k protein significantly decreased (total IgM 1.3 g/l). Electrophysiological studies improved, but only 8 months after therapy (motor ulnar and median CV 17 m/s, distal latency 7.7 and 7.1 ms, respectively; mild signs of reinnervation appeared). At month 13, the haematological parameters persisted stable, with no need of maintenance therapy.
The dramatic improvement after rituximab administration seems to support a role of B cells in the pathogenesis of CIDP, at least in cases associated with IgM lymphoproliferative diseases, regardless of the presence of antibodies to peripheral nerve antigens.
Rituximab may, therefore, be considered in CIDP refractory to conventional therapies.
John Martin is a long-time health journalist
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