Page 946 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 67 Autoimmune Peripheral Neuropathies 913

High-Dose Intravenous Immunoglobulin
1,4
On the basis of the results from two controlled studies, IVIG
(Chapter 84), given at 2 g/kg over 2–5 days, has been shown to be
equally effective as plasmapheresis, with no added benefit when
the two procedures were combined. The decision as to which
treatment to choose is governed by circumstances, availability
of the treatment modality, experience, age of the patient, and
other associated conditions. Early relapses can also occur with
IVIG, as often as with plasmapheresis. IVIG has become the
therapeutic choice worldwide because it is easy to administer
and more readily available and because time to initiate treatment
is of the essence.
Steroids are ineffective in GBS and may even increase the
incidence of future relapses. Combining IVIG with IV methyl-
FIG 67.6 Cross-section of a root from a patient with human prednisolone has shown no significant added benefit.
immunodeficiency virus (HIV)–associated Guillain-Barré syndrome
(GBS) shows cytomegalovirus inclusions within the Schwann Chronic Inflammatory Demyelinating Polyneuropathy
cell. Prednisone
CIDP has been originally described as a classic steroid-responsive
polyneuropathy. The efficacy of steroids was proven in a controlled
study, albeit with inadequate blinding, but reconfirmed in
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occurs later in the disease. It is caused by a cumulative effect, another. 2,3,11,12,39 A high-dose regimen of 80–100 mg prednisone
on the peripheral nerves, of various endogenous or exogenous daily is preferred, followed by tapering to every-other-day dosing.
neurotoxins related to a multisystem disease and dysfunction of Azathioprine, cyclosporine, or mycophenolate can be used as
many organs along with toxicity from various antiretroviral drugs. steroid-sparing agents, but their efficacy, although not tested in
Clinical findings include distal painful dysesthesias, sensory loss controlled studies, has been disappointing overall. Methotrexate
or hypesthesia, areflexia, and, in advanced cases, distal weakness. in a controlled study was ineffective. 2,3,11,12,39
Despite the relative lack of motor involvement, the severity of
neuropathic pain can be disabling. Intravenous Immunoglobulin
In several controlled studies, 2,3,11,12,39 IVIG has been effective in
TREATMENT the majority of patients with CIDP. The more chronic the disease
and more severe the axonal degeneration that has taken place,
APNs are clinically important because they are potentially treatable the lower are the chances that the recovery will be complete or
with various immunosuppressive, immunomodulating, or significant. IVIG, in the largest-ever controlled study, has been
chemotherapeutic agents. The selection of an effective protocol proven an effective first-line therapy, and maintenance therapy
is based on the results of experimental therapeutic trials, clinical has prevented relapses.
experience, and the risk–benefit ratio of available therapies. The
author’s approach to the treatment of these disorders is described Plasmapheresis
below. Plasmapheresis has been also effective in controlled studies. 2,3,11,12
After a series of six plasma exchanges, maintenance therapy,
Guillain-Barré Syndrome with one exchange at least every 8 weeks, may be required if this
Supportive Care therapy is beneficial. IVIG has now replaced plasmapheresis,
The dramatic reduction in the mortality of GBS is mainly although in the author’s experience, some patients may benefit
attributed to the availability of ICUs, improvement of respiratory more from steroids, others more from IVIG, and still others
support, antibiotic therapy, and control of autonomic cardiac more after plasmapheresis.
dysregulation. A patient with GBS is best monitored in an ICU,
even if respiratory compromise is not evident at the time of Polyneuropathy With Paraproteinemias
admission. When forced vital capacity (FVC) drops or bulbar Patients with benign IgG or IgA demyelinating polyneuropathies
weakness is severe, intubation is necessary. respond in a manner similar to CIDP patients. Patients with
malignant paraproteinemias should be treated with chemotherapy,
Plasmapheresis as needed for the underlying disease. When the neuropathy is
In several double-blind controlled studies, plasmapheresis has axonal, treatments are generally disappointing.
been shown to be effective if performed within the first week For IgM anti-MAG demyelinating polyneuropathies, treatments
from onset of the illness. A series of five or six exchanges, with with prednisone plus chlorambucil, plasmapheresis, and IVIG 2,3,40
one exchange every other day, is sufficient. Early relapses can has shown a variably marginal benefit. Rituximab, an mAb against
41
occur in up to 20% of patients, who may require a second series CD20, is the most promising therapy, providing efficacy in
1-5
of plasma exchanges. Plasmapheresis has been shown to be almost 40% of the patients in a small double-blind study, as
33
effective even in mild cases of GBS; two exchanges are sufficient confirmed later with a larger study, even though both did not
for mild GBS, and four are optimal for moderate cases, but there reach significance. Additional, uncontrolled series with many
is no difference between those who receive four plasma exchanges patients, have confirmed that rituximab is effective in 30–40%
and those who receive six. of these patients.