Page 1182 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 84 Immunoglobulin Therapy: Replacement and Immunomodulation 1147

CLINICaL PEarLS 2 successfully with conservative therapy, but deaths were reported
Adverse Events Associated With in 17 patients who had serious underlying conditions. Most
cases of this adverse event were associated with IVIG
Immunoglobulin Therapy products containing sucrose as a stabilizer. Risk factors for this
rate-related adverse reaction include preexisting renal insufficiency, diabetes
• Infusion site erythema, swelling, pain, itching mellitus, dehydration, patient age >65 years, sepsis, paraprotein-
• Headache emia, and concomitant use of nephrotoxic agents. Newer IVIG
• Myalgia, back pain, arthralgia products are using alternative stabilizers (e.g., amino acids) instead
• Malaise, fatigue of sucrose.
• Chills, Fever
• Pruritus
• Rash—urticaria
• Nausea, vomiting CLINICaL PEarLS 3
• Tachycardia Risk Factors for Adverse Events
• Dyspnea, chest pain, or tightness
• Hypotension/hypertension
• Infusion issues
• Prior history of an infusion reaction with an immunoglobulin (Ig)
Central Nervous System product
• Severe headaches • First infusion in a patient with active infection or inflammation
• Trigger migraine headaches • Changing immunoglobulin products
• Aseptic meningitis* • Rapid infusion and/or large dose
• Patient factors
renal • Preexisting renal insufficiency
• Azotemia • Prior history of thrombotic event
• Renal failure • Autoimmune disorder
• Diabetes mellitus
Thromboembolic Events* • Age—older age
• Thrombosis/cerebral infarction • Hyperlipidemia or elevated cholesterol
• Myocardial infarction • Dehydration with volume depletion
• Pulmonary embolism • Hypercoagulable state
• Indwelling catheters
• Paraproteinemia or other causes of hyperviscosity
anaphylaxis From anti-Immunoglobulin E (IgE) antibodies to Iga
• Cardiac or peripheral vascular disorders
• Estrogen use
Other (Isolated reports) • Smoking
• Cardiac rhythm abnormalities
• Coagulopathy
• Serum sickness
• Hemolysis—alloantibodies to blood type A/B
• Cryoglobulinemia Thromboembolic Events
• Neutropenia This adverse effect was observed mainly in patients receiving
• Alopecia large doses of IVIG for autoimmune diseases. Patients with
• Uveitis elevated serum viscosity (e.g., cryoglobulinemia, hypergam-
• Noninfectious hepatitis
• Progressive neurodegeneration maglobulinemia, and hypercholesterolemia) are at risk for
developing a critical increase in serum viscosity with IVIG,
*See text for predisposing risk factors. especially high doses that predispose them to thromboembolic
events, such as myocardial infarction, stroke, deep vein thrombosis,
or pulmonary embolism. (Clinical Pearls 3) Recently, a contami-
nating procoagulant factor (e.g., factor XIa) has been implicated
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including headache, stiff neck, and photophobia, usually develop in these thromboembolic events. Patients at risk are older (>65
within 24 hours after completion of the infusion and may last years), on multiple drugs, and have comorbidities, such as diabetes,
3–5 days. Spinal fluid pleocytosis occurs in most patients. Long- hypertension, and so on. Patients at risk should be well hydrated,
term complications are minimal. The etiology of aseptic meningitis IVIG should be administered at lower rates, and products with
is unclear, but migraine has been reported as a risk factor low sodium and an osmolality in the physiological range should
and may be associated with recurrence despite the use of be selected. Ig manufacturers have taken steps to remove or
different IVIG preparations and slower rates of infusion. (Clinical reduce this procoagulant activity from their products. 23
Pearls 2)
Transfusion Reaction Caused by Antibodies Against IgA
Renal Adverse Events True anaphylaxis is rare in patients with selective IgA deficiency
Acute renal failure is a rare but significant complication of IVIG and CVID who develop IgE antibodies to IgA after treatment
treatment and has been associated in the past with products with Ig; this adverse event appears to be much less frequent than
containing sucrose. Histopathological findings of acute tubular originally thought. Patients with CVID have IgG antibodies
necrosis, vacuolar degeneration, and osmotic nephrosis were (10–22% in various studies) to IgA, but there is no correlation
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suggestive of osmotic injury to the proximal renal tubules. Most to the presence of these antibodies and adverse reactions. Patients
patients (95%) had received large doses for treatment of auto- with anti-IgA antibodies who have had reactions to IVIG have
immune diseases. The majority of the cases were treated tolerated SCIG. 25