Intravenous immunoglobulin (IVIG)

Intravenous immunoglobulin (IVIG)

  • Predominantly immunoglobulin G (IgG), with trace amounts of Immunoglobulin A (IgA) pooled from human plasma
  • Pregnancy Category C (crosses placenta & excreted in breast milk)
  • ½ life: 3-5 weeks
  • 60% distributed intravascularly & 40 % extravascularly

Doses

  • 2-3 g/kg /cycle divided over 2-3 days (one dose 2gm/kg over 10-12h in Kawasaki)
    or
  • 400 mg/kg/day x5 days (slow infusion over 4-5h)

During infusion

  • Monitor blood pressure, heart rate, & signs of volume overload
  • Decreasing rapidity of infusion lessens risk of thromboembolic events, aseptic meningitis, & cardiovascular/ renal events 

Maintenance 

  • Repeat monthly (or every 2 weeks in severe cases) until disease stable 
  • Taper by increasing interval between infusions

Effect on humoral immunity

  1. Decreased antibody production
    • Binds Fc receptor on B-cells leading to decreased Antibody production
    • Decreasing half-life of circulating immunoglobulin G (IgG) via increased catabolism
  2. Antagonize auto-antibody
    • Contains antibody that neutralize pathogenic antibody
  3. Decreased cell activation (macrophages)
    • Bind to Fc receptors on macrophages inhibiting auto-antibody medicated cellular activation
  4. Neutralizing antibody to bacterial/viral superantigen 
    • Decreased non-specific activation of T-cells

Effect on cell-mediated immunity

  1. Decreased activation
    • Contains CD4, CD8, major histocompatibility complex, providing negative feedback leading to decreased Lymphocyte function-associated antigen (LFA) (co-stimulatory molecules on activated T cells) & subsequent decreased T cell activation
  2. Restoration of T-helper 1 & 2 (Th1/Th2) balance of cytokines
  3. Cell migration
    • Inhibits adhesion & transmigration
  4. Decreased cytotoxic response
    • Anti-Fas receptor Antibody prevents keratinocyte apoptosis (in toxic epidermal necrolysis (TEN)

Decreased Complement

  • Binds C3& C5 convertases blocking complement activation & formation of membrane attack complex

Other: Synergistic with corticosteroids

  • Increase sensitivity of glucocorticoid receptor & synergistically decrease T-cell activation

Food & drug administration (FDA)

  • Primary & secondary immunodeficiencies

Off label (Bolded conditions: most optimal response)

  • Vasculitides:
    • Kawasaki: Autoimmune connective tissue disease – Dermatomyositis/polymyositis, systemic lupus erythematosus, scleroderma
    • Bullous dermatoses: pemphigus vulgaris, pemphigus foliaceous, bullous pemphigoid, pemphigoid gestationis cicatricial pemphigoid, epidermolysis bullousa acquisita (EBA), linear IgA bullous dermatosis, Steven Johnson syndrome / Toxic epidermal necrolysis: Inflammatory: chronic spontaneous urticaria, atopic dermatitis, graft versus host disease, psoriasis, pyoderma gangrenosum
    • Others: Livedoid vasculopathy, scleromyxedema, pretibial myxedema, necrobiotic xanthogranuloma

Absolute

  • Hypersensitivity to Intravenous Immunoglobulin (IVIg)

Relative

  • Immunoglobulin A (IgA) deficiency (↑anaphylaxis due to trace of Immunoglobulin A (IgA) in Intravenous Immunoglobulin (IVIg))
  • Congestive heart failure (risk of volume overload)
  • Renal failure (risk of volume overload)
  • Rheumatoid arthritis (Increased risk of renal failure)
  • Cryoglobulin (Increased risk of renal failure)

Pregnancy & lactation

  • No contraindication
  • No associated risk with lactation

Infusion related (30-60 minutes after infusion)

  • Headache, nausea & vomiting, myalgia, chills, flushing, fever, lower back pain, wheezing, chest pain, blood pressure changes & tachycardia
  • With mild side effect: slow infusion or stop 
  • Can pre-treat with non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, & corticosteroid

Anaphylaxis

  •  Reported with Immunoglobulin A (IgA) deficiency

Fluid overload

  • In renal or cardiac disease

Acute renal failure

  • Due to “osmotic nephrosis” in sucrose containing preparations

Hematologic effects

  •  Neutropenia & hemolysis 

Neurologic effects

  • Aseptic meningitis (self-limited, 11% If given for neurological diseases)

Thromboembolic events

  • Cerebrovascular accidents /myocardial infarct, due to increased osmolality/ viscosity 

Theoretical infection risk

  • Due to pooled human plasma

Cutaneous

  • Dyshidrotic eczema & pompholyx

Baseline

  • History + Physical/exam (cardiopulmonary, weight)
  • Complete blood count, liver functions, creatinine, Immunoglobulin A (IgA) levels, Rheumatoid factor, cryoglobulins
  • Consider Hepatitis B/C, & human immunodeficiency virus (HIV)

Follow-up

  • No specific lab testing is needed

Consider Intravenous Immunoglobulin (IVIg)

  • For progressive, uncontrolled, or rapidly debilitating disease despite conventional therapy
  • Contraindications (relative or absolute) to the use of high dose long-term corticosteroid or immunosuppressant agents
  • Significant adverse effects from conventional therapy that are potentially life threatening, or cause significant morbidity or inability to carry out daily activities