I.V.I.G

BY: MOHAMMED ALSAIDAN

IVIG

• IVIg is a blood product derivative manufactured from the sterilized, purified human plasma of between 1000 to 20,000 donors per batch.

• The final IVIg preparation is primarily composed of IgG, with trace amounts of IgA, IgM and albumin

• half-life of IVIg ranges from 3-5 weeks

• Crosses the placenta, and may be excreted in milk

• Distributed : 60% intravascular , 40 % extravascular

MOA

• Functional blockade of the Fc receptors

• Neutralize complement , and block complement activation in early stage

• Anti-idiopathic antibodies can neutralize pathogenic antibodies

• Interfere with T-cell activation

MOA

• Interfere with cellular migration

• Increase glucocorticoid receptor sensitivity

• In toxic epidermal necrolysis, IVIg blocks Fas (CD95) mediated keratinocyte death by inhibiting Fas – Fas ligand interactions

Indications

• The efficacy of IVIg is best documented in patients with:• graft-versus-host disease• Kawasaki’s disease• dermatomyositis

• Autuimmune bullous dermatosis:• pemphigus vulgaris• pemphigus foliaceus• bullous pemphigoid• herpes gestationis• epidermolysis bullosa acquisita (EBA)• TEN/ SJS

Indications

• Other indications: • Atopic dermatitis• psoriasis• scleroderma• Pyoderma gangrenosum• Chronic autoimmune urticaia

When to use IVIG for bullous dis.

1)Progressive, uncontrolled,or rapid debilitating diseasefailure of conventional therapy2) significant adverse effects from conventional therapy3) contraindications, relative or absolute, to the use of high-dose long-term systemic therapy

*The patient age and pregnancy are not contraindications to the use of IVIG

Before starting IVIG

• Vital signs • Weight to monitor for overload• Auscultate lungs and heart • Labs: • CBC• LFT • Renal profile• Immunoglobulin levels• RF and in patients at an increased risk of acute renal failure• For medicolegal reasons: HBV, HCV and HIV is advisable

Pre medication

• To minimize the risk of infusion-related side effects, such as headaches, myalgias and rigors.• Analgesics (i.e., acetaminophen)• Antihistamines (i.e., diphenhydramine) • NSAID (i.e., celecoxib)• low-dose intravenous corticosteroids may be of benefit to a

subset of individuals

Dosage

• The most common dosage in dermatology is 2 g/kg/cycle divided into 3 equal doses in 3 consecutive days

• Or 400mg/kg daily for 5 days

• Infusion: Slowly over 4 to 4 ½ hours

• Given monthly , but can be given every 2 weeks in very aggressive disease

• Tapering : keep the same dose with increasing the interval between infusions by 2 weeks (4,6,8,10,12,14,16) then D/C

Dosage

• Careful monitoring for 1st infusion or different preparation

• All patients must be well hydrated prior to the infusion .

• When all these measures fail to correct or prevent the adverse reactions it could be useful to change to a different preparation of IVIG

Anaphylaxis reaction

• More frequently with antibody deficiency , mainly in IgA deficiency with antibody against IgA

• Slow infusion seems to lower the risks

• Resolve with temporary interruption of the infusion or a slowing of its rate of administration

• Can be prevented by giving , paracetamol or anti-histamines before the treatment and/or hydrocortisone during it.

Thromboembolic events

• Secondary to increased viscosity , leading to cerebral or myocardial infarction

• RISK FACTORS:• higher doses or rapid infusion • elderly patients• patients with previous cerebral or cardiac ischaemia• overweight patients• Those who are markedly hypovolaemic and immobilised

Aseptic menengitis

• observed in patients with neurological and neuromuscular diseases treated with high doses of IVIG.

• The symptoms appear within 6–24 hours of the end of the infusion and disappear without sequelae in 3–5 days

Renal disease

• Increases in creatinine or acute renal failure rarely in elderly, diabetic, poorly hydrated patients, with pre-existing renal disease or who are taking nephrotoxic drugs.

• These problems are probably related to damage caused to the renal tubules by the saccharose included in various preparations as a stabiliser.