Treatment Considerations

Selection and Administration

All proprietary preparations of IVIg are more or less similar inefficacy, safety, and cost. Although the different pools of human donors used by diversed manufacturers enclosed a wide range of anti-idiotypic antibody specificities, no deviation in the efficacy of a certain product or a specific disease has been documented.

The therapeutic dose of IVIg is empirically set at 2 g/kg. Even if some practitioners divide the total dose for . infusion into five daily doses of 400 mg/kg each, it may be preferable to divide the total dose into two daily doses of 1 g/kg each, provided that the patient does not have such underlying conditions as congestive heart failure, renal insufficiency, or high serum viscosity. In view of the drug's rapid diffusion to the extravascular space, obtaining a high concentration of IVIg within 2 days may increase efficacy. Experimental studies in both vitro and vivo have suggested a superior effect on cytokine neutralization, Fc receptor manipulation, and inhibition of C3 fragments when IVIg concentrations equivalent to 2 g/kg were given in a bolus infusion rather than in divided doses. In children with Kawasaki syndrome, one 2-g/kg dose of IVIg given in a 10-hour infusion was more effective than four daily infusions of 400 mg/kg each. In long-term therapy, the IVIg infusion is repeated every 4 to 8 weeks according to patient response and objective signs of disease recurrence. The efficacy of lower doses of IVIg in maintaining improvement remains to be determined.

Adverse Reactions and Risk Factors

Conflicting reactions to IVIg therapy are usually minor and occur in no more than 10% of patients. Mild-to-moderate headache, which responds to nonsteroidal anti-inflammatory drugs is average. Chills, myalgia, or chest discomfort may foster in the first hour of the infusion and most of the time respond to cessation of the infusion for 30 minutes and resumption of it at a slower rate. Fatigue, fever, or nausea may occur after infusion and may last as long as 24 hours. The cause of these reactions is unclear, but activation of complement by aggregated immunoglobulin molecules or various stabilizing agents in the IVIg preparation has been associated. A slow rate of infusion is apt in patients with a compromised cardiovascular system or congestive heart failure to elude rapid fluid overload.

More so, increases of creatinine and blood urea nitrogen (BUN) have been discerned as soon as one to two days following infusion of IGIV. Development to oliguria and anuria requiring dialysis has been observed, although some patients have advanced spontaneously following cessation of treatment.

Serum Viscosity and Thromboembolic Events

Therapy with IVIg increases serum viscosity. In patients with high normal serum viscosity in conditions like cryoglobulinemia, hypercholesterolemia, or hypergammaglobulinemia, viscosity increases even further. Serum viscosity greater than 2.5 centipoise augments the risk for thromboembolic events, which probably accounts for the rare cases of stroke or pulmonary embolism after IVIg therapy. Therapy with IVIg can also induce a hyperviscosity syndrome in children with HIV infection who have high pretreatment levels of serum immunoglobulins. Reversible cerebral asospasm has happened in a patient treated with IVIg.

Possible Effects On Patients Receiving IVIg Therapy

The following are possible effects of IVIg Therapy to patients:

• Migraine Headache.
  If a patient have a history of migraine, IVIg therapy may trigger a migraine attack. This can sometimes be avoided by propranolol prophylaxis. The incidence of aseptic meningitis is also high in these patients.
• Aseptic Meningitis
  This develops in as many as 10% of patients treated with IVIg and is not related to the commercial source of the IVIg product. Prophylaxis with intravenous steroids is often ineffective. The symptoms respond to strong analgegsia and subside in 24 to 48 hours.
• Skin Reactions
  Skin reactions to IVIg therapy are rare. They mature in 2 ro 5 days after infusion and may last for as long as 30 days. They include urticaria, pruritus of the palms. And petechiae of the extremities. Alopecia and leukocytoclastic vasculitis arising in a patient with cryoglobulinemia are other highly rare reactions to IVIg.
• d. Sever Anaphylactic Reactions
  This may occur in patients who have a grave deficiency of IgA associated with anti-IgE or anti-IgG antibodies against IgA. The reaction is rare and occurs primarily in patients with common cariable immunodeficiency. Yet, we routinely determine the serum IgA level before starting therapy.
• Renal Tubular Necrosis
  This is usually reversible. It occurs seldom with IVIg therapy in patients who have pre-existing kidney disease and volume depletion. This happens specially to elderly people, to the diabetic, or poorly hydrated patients. This complication has been associated with the high concentration of sucrose in one proprietary IVIg product. Osmotic tubular nephrosis, caused by intravenous solutions containing a concentration of hypertonic sucrose tothat in IVIg preparations, is also a rare reaction.

Cost of Treatment

Plasmapheresis is almost as expensive as the IVIg therapy. Howeevr, it is not readily available, and usually has more unfavorable effects. Corticosteroids or immunosuppressants are less expensive than IVIg. But it can be costly in terms of iatrogenic complications with long-term use and the potential loss of wages associated with inadequate disease control.

Cost will strongly influence the choice of therapy. The other factors like the adverse effects of long-term treatment, the medical costs of treatment complications, the patient's safety, comfort, quality of life and potential for a faster and better therapeutic reaction must also be considered.

Medicine has its office, it does its share and does it well; but without hope back of it, its forces are crippled and only the physician's verdict can create that hope when the facts refuse to create it.

- Mark Twain -