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Montreal,
QC—There
are approximately 13 dermatological indications for intravenous
immunoglobulin therapy, but its best accepted uses in dermatology
are for toxic epidermal necrolysis and pemphigus vulgaris, Neil
H. Shear, MD, PhD, said at Dermatology Update.
Other dermatological uses include: pemphigus foliaceus, bullous
pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita,
atopic dermatitis, Kawasaki disease, dermatomyositis, pyoderma gangrenosum,
erythema multiforme, pemphigoid gestationis, chronic urticaria,
toxic epidermal necrolysis, and pemphigus vulgaris.
Intravenous immunoglobulin (IVIG) is a concentration of human antibodies
obtained from donated, pooled plasma. “It’s not a monoclonal
antibody. It’s really a superphysiological dose of immunoglobulin,”
said Dr. Shear, professor and chief, division of dermatology, University
of Toronto, and head of dermatology at Sunnybrook and Women’s
College Health Sciences Centre.
IVIG is mainly composed of monomeric IgG, with small amounts of
IgA and IgM. No one knows how it works. “It may work through
a combination of human antibody replacement and immune modulation.
“It may also increase the degradation of IgG,” he said.
Toxic epidermal necrolysis (TEN)
TEN is rare, with an incidence of about one in one million. “I
see about five to eight people each year in the burn centre at Sunnybrook,”
he said.
The diagnosis may seem obvious clinically, but a biopsy for histology
and immunofluorescence is needed to confirm a diagnosis because
TEN can look like other diseases, such as Chan’s disease and
acute generalized exanthematous
pustulosis.
The IVIG protocol is 1 g/kg per day for three days. Duration is
three days because a total dose of more than 2.4 g/kg is needed
and a total dose of 3 g/kg is acceptable.1 In a retrospective multicentre
analysis of patients who had at least 10 per cent of their body
surface affected, IVIG was found to be safe and effective for ceasing
skin and epidermal detachment and improving survival rates.2 A third
study3 showed that IVIG 1-to-4 g/kg delays progression of TEN and
Stevens-Johnson syndrome and reduces mortality by 83 per cent. However,
a fourth study4 indicated that IVIG does not slow disease progression
or reduce mortality.
The current literature is problematic because there have been no
randomised clinical trials, different doses have been used, different
outcomes have been evaluated, and different clinical conditions
have been included. Yet IVIG is recommended as a therapy for TEN
by Health Canada.
“If it’s TEN, your transfusion people should be able to
say, ‘Yeah, we understand. We’re going to give it for
that,’” Dr. Shear said. “Sure the evidence is anecdotal,
but it may be effective early on in the course, and you might save
lives and reduce death rates.”
Pemphigus vulgaris
The evidence is anecdotal for pemphigus vulgaris, he said. “But
the evidence does support IVIG as adjunctive, or as second-, third-,
or fourth-line therapy if conventional treatment is ineffective
or, perhaps, inappropriate.”
Although not as rare as TEN, pemphigus vulgaris is uncommon. It
has an incidence of between one and five in 100,000. “I see
about 20 new people a year at the hospital.”
The protocol is 2 g/kg in a five-day cycle.5 “Now the beauty
of this is that if you do it over two days and somebody weighs 58
kg, you know that they need 58 g. Anybody can multiply 58 times
one and get 58. Remember, they’re grams. We’re so tempted
to order things in milligrams. If you do that, I suspect that, although
it will be cheaper, your response rates will be much lower,”
he joked.
For pemphigus vulgaris, IVIG therapy is given once a month for about
four or five months (at which point there is usually a clinical
response) and then once every six to eight weeks. Treatment lasts
two years for most patients.6
IVIG is associated with adverse reactions in fewer than one per
cent of patients. They are usually mild and self-limiting (eg, headache,
back pain, chills, flushing, fever, hypertension, myalgia, nausea,
and vomiting). These reactions may be linked to infusion rate rather
than dose. High infusion rates and high doses may be risk factors
for thrombotic events in people at risk for such events.
“Canadians do use lots of IVIG,” Dr. Shear said. About
two million grams of IVIG are used each year, of which six per cent
is for dermatological conditions.
Canadian Blood Services provides four licensed IVIG products:
• CBS/Hema-Quebec IVIG,
• Gamimune® N,
• Gammagard S/D, and
• Iveegam.
The newest product is Gamunex™. It requires significantly fewer
steps during preparation, has a 70 per cent shorter processing time,
yields up to 30 per cent more IgG, and produces a more purified
final product. As the therapy can be given at much faster rates,
it may reduce infusion time by as much as 50 per cent.
Physicians may download data on IVIG therapy for dermatological
conditions on websites from two provincial panels:
www.bloodlink.bc.ca/documents/ivighandbook3.pdf, and
www.lhsc.on.ca/lab/bldbank/assets/bloodye.pdf.
References
1. Prins C, Kerdel FA, Padilla RS, et al.
Treatment of toxic epidermal necrolysis with
high-dose intravenous immunoglobulins: Multicenter retrospective
analysis of 48 consecutive cases. Arch Dermatol 2003;139(1):26-32.
2. Stella M, Cassano P, Bollero D, et al. Toxic epidermal
necrolysis treated with
intravenous high-dose immunoglobulins: Our experience. Dermatology
2001;203(1): 45-49.
3. Bachot N, Revuz J, Roujeau JC. Intravenous immunoglobulin treatment
for Stevens-Johnson syndrome and toxic epidermal necrolysis: A prospective
noncomparative study showing no benefit on mortality or progression.
Arch Dermatol 2003;139(1)33-36.
4. Trent JT, Kirsner RS, Romanelli P, Kerdel FA. Analysis of intravenous
immunoglobulin for the treatment of toxic epidermal necrolysis using
SCORTEN: the University of Miami Experience. Arch Dermatol 2003;139(1):39-43.
5. Ahmed AR, Dahl MV. Consensus statement on the use of intravenous
immunoglobulin therapy in the treatment of autoimmune mucocutaneous
blistering disease.
Arch Dermatol 2003;139(8):1051-1059.
6. Ahmed AR. Intravenous immunoglobulin therapy in the treatment
of patients with
pemphigus vulgaris unresponsive to conventional immunosuppressive
treatment. JAAD 2001;45(5):679-690.
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