C. Briania, G. Zaraa, R. Zambellob, L.Trentinb, M. Ranac and F.
Zajad Departments of aNeurosciences and bClinical Immunology, Departments of Neurology and
Hematology, University of Udine, Udine, Italy
Chemotherapy has been used for treating chronic inflammatory
demyelinating polyradiculoneuropathy (CIDP) with incosistent
results. Chemotheraphy has been
used for treating with inconsistent results. Rituximab is a chimeric
monoclonal antibody directed against the CD20 antigen, used to treat
B-cell lymphoma and reported
to 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.
to 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 muscle
denervation 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 his
daily 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
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