IgG
Introduction
Pediatric AIDS
Because AIDS is an
acquired immunodeficiency, it is reasonable to consider
the use of IVIG therapy in pediatric patients with HIV
infection, given the success of IVIG in primary
immunodeficiencies. To date, small, uncontrolled studies
have suggested the efficacy of IVIG in pediatric AIDS by
decreasing the morbidity from common bacterial
pathogens, as well as measles, but no controlled studies
have been completed. Currently, the National Institutes
of Health (NIH) is sponsoring two large, controlled
trials of IVIG with and without zidovudine (AZT) in
HIV-infected children. A definitive assessment of the
efficacy of IVIG in pediatric HIV infection awaits the
results of these trials.
Infections in Low Birth
Weight Infants
Prevention of infection
in low birth weight infants
Premature infants have
insufficient placental transfer of maternal IgG and have
been demonstrated to have low levels of serum IgG.
Hence, it is reasonable to consider IVIG prophylaxis in
premature infants. Some pilot studies indicated a lower
rate of severe infection in IVIG-treated low birth
weight infants compared with placebo-treated patients.
In a recently completed randomized, double-blind,
placebo-controlled trial involving a large number of
infants with birth weights of 500-1500 grams, it was
noted that mortality was not significantly reduced among
IVIG recipients. However, the number of infections was
significantly reduced among IVIG recipients. It should
be noted that there was some evidence that beneficial
effect may vary by birth weight category, and
significantly more placebo patients were small for
gestational age. Information about long-term results
(greater than 56 days) is not available from this trial.
Moreover, preliminary analysis of other trials indicates
no significant difference in infection rates between
IVIG recipients and placebo recipients. However,
differences in study design make direct comparison of
the various trials difficult. Further information will
become available as a result of the ongoing trial
sponsored by the NICHD Neonatal Research Network. At
this time, IVIG cannot be recommended as standard
prophylaxis of low birth weight infants.
Treatment of presumed
neonatal infection
To date, small trials
using primarily historical controls have yielded mixed
results. Questions remain concerning dose, schedule, and
patient selection. Variability in preparations and lots
creates a number of difficulties in predicting results
of treatment for specific organisms. There is a
potential role for directed preparations containing
specific antibodies. Furthermore, studies in neonatal
animals have shown that in some situations survival is
less with high concentrations of IVIG plus antibiotic
compared with antibiotic alone. The routine use of IVIG
as adjuvant therapy of neonatal infections cannot be
recommended at the present time.
Bone Marrow
Transplantation
In a large study of bone
marrow transplant recipients, reduced rates of
septicemia and local infection were noted for IVIG-treated
patients (500 mg/kg weekly) compared with untreated
controls. Several studies have shown a decreased rate of
acute graft versus host disease (GVHD) in patients
receiving IVIG, 500 milligrams to 1 gram per kilogram
weekly. Results of limited trials suggest that in
pediatric bone marrow recipients, reduction in infection
and death but not GVHD has been associated with IVIG
administration.
It has been noted that
IVIG decreases the incidence of interstitial (presumably
CMV) pneumonia but is ineffective in preventing CMV
infections. IVIG plus ganciclovir is beneficial in
treating CMV pneumonia in patients who are not
ventilator dependent.
Chronic Lymphocytic
Leukemia
A study in 10 centers in
which 57 patients with CLL were followed for 1 year of
observation has been completed. The incidence of major
and moderate bacterial infections was significantly
reduced in hypogammaglobulinemic CLL patients who
received IVIG. The number of trivial infections was
unchanged by intravenous immunoglobulin. Maintenance of
serum IgG levels > 640 mg/dL tended to correlate with
fewer infections, especially serious bacterial
infections. The data support the conclusion that IVIG
may be useful to prevent serious infections in patients
with CLL with hypogammaglobulinemia.
Idiopathic
Thrombocytopenic Purpura
Among children with ITP,
the use of IVIG has been documented to increase platelet
counts. This treatment is utilized in the rare pediatric
patient with potentially life-threatening bleeding
(e.g., 400 mg/kg/d x2-5 or 1 g/kg/d x1 or 2). A number
of therapeutic options are available for managing the
child with newly diagnosed ITP who does not have serious
hemorrhage: IVIG, corticosteroids, or close observation
without therapy. IVIG has been used in chronic ITP to
postpone the requirement for a splenectomy. There is no
firm evidence of curative effects in either acute or
chronic ITP. Responses appear to be similar with
different manufacturers' products licensed for this
purpose.
In adult patients with
ITP, IVIG, at the doses indicated above, has also been
used for the rapid correction of life-threatening
thrombocytopenia, with or without corticosteroids.
Administration every 10 to 21 days is usually required
to maintain adequate platelet counts. Other indications
include administration to steroid-refractory patients
preoperatively. In addition, IVIG may be employed at the
same dosage in patients who cannot use corticosteroids
and in patients with immunodeficiency including those
with HIV-associated thrombocytopenia. Although IVIG
administration before scheduled splenectomy is
effective, cost/benefit relationships are unclear
because of the low incidence of complications during
this procedure, even with extremely low platelet counts.
Kawasaki Syndrome
Studies of IVIG in
Kawasaki syndrome using 400 mg/kg daily for 4 days
indicate a prompt anti-inflammatory response in the
acute phase and a significant decrease in the formation
of coronary aneurysms compared with low/moderate aspirin
administration regimens. More recently, a dosage
schedule of 2 g/kg as a single administration has been
shown to be at least as effective as the four-dose
schedule. Complications of the larger single-dose
administration were few. A smaller study using 1 g/kg as
a single dose also seemed to suggest similar efficacy to
the four-dose regimen.
IVIG and aspirin
administration has become a standard treatment for
Kawasaki syndrome. The panel agrees that on the basis of
available studies, IVIG administered as a single dose of
2 g/kg is effective therapy for patients who fulfill the
diagnostic criteria for Kawasaki syndrome. Treatment of
patients recognized after the tenth day of the disease
has not been studied systematically.
The advantages of
treating patients with Kawasaki syndrome with IVIG as
early as possible must be balanced against the
probability that children with other inflammatory
diseases will also be treated inadvertently. There is no
evidence that this latter group of children will be
benefitted.
Chronic Inflammatory
Demyelinating Polyneuropathies
Several small studies
have shown positive responses to IVIG in the majority of
treated patients. Treatment needs to be periodically
repeated to prevent relapse. When considered in
comparison with customary treatments, IVIG may be easier
to use and associated with fewer complications than
repeated therapeutic plasma exchange and long-term
glucocorticoids, respectively.
Guillain-Barré Syndrome
In a preliminary analysis
of a large, randomized multicenter trial of IVIG
compared with therapeutic plasma exchange, there is an
indication of improved functional recovery for patients
receiving IVIG. Definitive conclusions regarding the
efficacy of IVIG in Guillain-Barré syndrome will need to
await the final analysis of this study and other
confirmatory studies.
Intractable Seizure
Disorders
A number of uncontrolled
studies and anecdotal reports have indicated benefit of
IVIG administration in children with intractable
seizures. The absence of randomized, double-blind
studies does not allow specific recommendations to be
made regarding such treatment. The panel emphasizes the
need for controlled human studies in this area.
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