Page 918 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHAPtER 65 Myasthenia Gravis 887

multicenter controlled trial completed recently compared clinical action most likely involves the removal of the pathogenic
outcome in patients with MG treated with corticosteroid versus autoantibody, as a reduction in titer of anti-AChR antibody
those treated with corticosteroid plus thymectomy and those correlates with clinical improvement. However, it is also possible
receiving thymectomy demonstrated a more favorable clinical that the removal of other phlogistic humoral factors contributes
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outcome. With improvements in preoperative care, anesthesia, to clinical efficacy.
surgical technique, and postoperative care, thymectomy has
become a safe procedure, but its value and safety in children Intravenous Immunoglobulin
and older patients is less well established. There is still some The efficacy of IVIG in the treatment for MG was suggested by
controversy over what represents the best surgical procedure. several uncontrolled clinical trials. Interest in the use of this
The mechanism responsible for the salutary effect of thymectomy biological grew out of its demonstrated efficacy in other auto-
remains to be elucidated. No obvious effects on immunoregulatory immune diseases, most notably autoimmune thrombocytopenia.
mechanisms have been demonstrated, although anti-AChR titers Subsequent randomized double-blind placebo-controlled trials
tend to fall months after the procedure. Thymectomy is also the provided proof of clinical efficacy. Conventional dosing is infusion
recommended treatment for patients of all ages suspected of of 2 g/kg divided over 5 days, although some practitioners prefer
having thymoma. to administer this dose over 2 days. In a randomized, controlled
trial a total dose of 1 g/kg was found to be as efficacious as a
Corticosteroids dose of 2 g/kg. IVIG therapy is generally associated with rapid
Corticosteroids are used in patients with generalized MG who clinical improvement in responsive patients, independent of
fail to respond to anticholinesterase agents or thymectomy and whether they had undergone thymectomy or were being treated
in patients needing optimization of their clinical condition in concurrently with corticosteroids or immunosuppressive agents.
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preparation for thymectomy. They are generally not used as In some patients, improvement was sustained over a period of
first-line agents to replace thymectomy but are used in patients several weeks. Improvement has not always been accompanied
with ocular myasthenia who fail to respond to anticholinesterases. by a consistent reduction in anti-AChR antibody titers. In general,
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Corticosteroids are initially given on a daily basis, with therapy IVIG and plasmapheresis appear to be equivalent in efficacy.
initiated in a hospital. This cautious approach is followed because However, there is a general impression that IVIG is preferable
of the fear of clinical deterioration that may occur in some patients because of better tolerance and less cost. The mechanism(s) of
during the introduction of corticosteroids. This concern resulted this apparent salutary effect is unknown, although there is
in some groups advocating initiation of alternate-day therapy, evidence IVIG contains antibodies directed against the idiotypes
which is not typically associated with clinical deterioration and of anti-AChR antibodies.
can be carried out on an outpatient basis. Daily corticosteroids
are usually started in patients with generalized MG at a dose Immunosuppressive Agents
>1 mg/kg prednisone. Patients should be continued on this dose Immunosuppressive drugs have been tried primarily in patients
until clinical improvement is maintained for several days, then who have failed treatment with anticholinesterases, thymectomy,
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gradually weaned off, and switched to alternate-day therapy. plasmapheresis, and corticosteroids. Most of the experience
With improvement sustained over several months, an effort has been obtained with azathioprine, which has strong antiinflam-
should be made to reduce the dose (usually in 5-mg decrements) matory effects as well as immunosuppressive activity. The dose
administered on alternate days. Although a Cochrane review of azathioprine has varied between 1 and 3 mg/kg/day, with
underscored the dearth of controlled trials, the improvement improvement seen between 5 and 20 weeks. The drug is usually
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rate is generally estimated to be 60–90%. Complete remission started at a lower dose and escalated weekly to achieve the
is rare, and most patients will require some dose of steroids maintenance dose. The patient should be followed with complete
indefinitely. The physician should be alert to the possibility that blood counts, particularly during the initiation of therapy, as
anticholinesterase requirements may decrease as the patient azathioprine has a suppressive effect on the bone marrow. A
responds to corticosteroids. white blood cell count below 2500 or a neutrophil count below
1500 should prompt a reduction or termination of the dosage.
Plasmapheresis The results of a randomized double-blind placebo-controlled
Plasmapheresis has enjoyed popularity since its introduction as trial indicated that the addition of azathioprine (2.5 mg/kg) to
an auxiliary treatment modality in patients with generalized MG alternate-day prednisolone was associated with a reduction of
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in 1976, particularly as a temporizing measure. It appears to the prednisolone dose, fewer treatment failures, longer remissions,
be most beneficial in patients in myasthenic crisis and in those and fewer side effects. 43
experiencing progressive deterioration despite treatment with There is considerably less experience in the treatment of
anticholinesterases and corticosteroids. Plasmapheresis has also steroid-unresponsive patients with cyclophosphamide, another
proved to be useful in preparing patients for thymectomy when powerful immunosuppressive agent. It is associated with more
their course is complicated by involvement of the bulbar and adverse effects and does not appear to offer any significant
respiratory musculature. Such patients may also require short- advantage over azathioprine when used in standard dosing
term plasmapheresis during the postoperative period. Plasma- regimens. High-dose intravenous cyclophosphamide therapy for
pheresis also appears to be particularly efficacious in anti-MuSK patients with MG refractory to conventional immunosuppressive
antibody–associated disease. There is no long-term benefit of agents has been investigated as an approach to immunoablate
plasmapheresis when added to prednisone. bone marrow and allow for subsequent repopulation by endog-
Although there are no hard and fast rules, the average exchange enous stem cells. Although durable responses were seen in some
is 1–2 L/day for 7–14 days. Improvement is usually observed patients in an early trial, this regimen is not readily available
within a few days of concluding the treatment course, although and should only be utilized in refractory patients under treatment
patients in crisis often benefit more quickly. The mechanism of in specialized centers.