What Are the Off-Label Uses for Intravenous Immunoglobulin Therapy?

Because intravenous immunoglobulin therapy increases a patient's immune response, doctors prescribe it in many circumstances in the hope it can help the patient heal when other treatments fail.

Intravenous immunoglobulin (IVIG) therapy is a treatment for people whose immune system is compromised due to a genetic disorder or an acquired disease. Immunoglobulins are antibodies in blood that protect people from infections. 

Intravenous immunoglobulins are prepared from pooled plasma of over 1,000 healthy blood donors, and the plasma is purified before administration. IVIG preparations primarily contain a type of immunoglobulin known as IgG which occurs naturally in people, without immunization or antigen exposure.

IVIG infusions are typically given every three or four weeks.

Intravenous immunoglobulin therapy works in two opposing ways:

• Suppresses the immune system in patients with
  • Autoimmune disorders
  • Solid organ or bone marrow transplants
• Boosts the immune system in people with immune deficiencies, and promotes healing in many diseases.

FDA-approved IVIG uses are for the treatment of following immune-related disorders:

• Primary humoral immunodeficiency
• Multifocal motor neuropathy
• B-cell chronic lymphocytic leukemia
• Immune thrombocytopenic purpura
• Kawasaki syndrome
• Chronic inflammatory demyelinating polyneuropathy

In addition to the FDA-approved conditions, intravenous immunoglobulin is used to treat several autoimmune and infectious diseases, as well as against conditions with no known cause. 

The National Guideline Clearinghouse (a U.S. government resource website for evidence-based clinical practice guidelines run by the Agency for Healthcare Research and Quality) has outlined off-label IVIG uses that include:

• Blood disorders
• Aplastic anemia
• Pure red cell aplasia
• Diamond-Blackfan anemia
• Autoimmune hemolytic anemia
• Hemolytic disease of the newborn
• Acquired factor VIII inhibitors
• Acquired von Willebrand disease
• Immune-mediated neutropenia
• Refractoriness to platelet transfusion
• Neonatal alloimmune/autoimmune thrombocytopenia
• Posttransfusion purpura
• Thrombotic thrombocytopenia purpura
• Hemolytic uremic syndrome
• Infections
• Prevention of infection in conditions such as:
• Low birth weight
• Solid organ transplantation
• Surgery
• Trauma
• Burns
• HIV infection
• Neurological disorders
• Epilepsy
• Pediatric intractable Guillain-Barre syndrome
• Myasthenia gravis
• Lambert-Eaton myasthenic syndrome
• Multiple sclerosis
• Rheumatologic conditions
• Rheumatoid arthritis (juvenile and adult)
• Systemic lupus erythematosus
• Lupus nephritis
• Systemic vasculitis
• Dermatomyositis
• Polymyositis
• Inclusion-body myositis

Pulmonary conditions

• Asthma
• Chronic chest symptoms

Other conditions

• Recurring miscarriages of pregnancy
• Wegener’s granulomatosis (inflammation of blood vessels in sinuses, nose, throat, lungs and kidneys)
• Corticosteroid-resistant severe Sweet’s syndrome (fever, painful rashes and high neutrophil levels in blood)
• Behcet’s syndrome (Inflammation in blood vessels)
• Adrenoleukodystrophy (genetic condition in which fatty acids build up and destroy the myelin sheath around nerve cells)
• Acute cardiomyopathy (heart muscle disease)
• Chronic fatigue syndrome
• Congenital heart block
• Cystic fibrosis (hereditary disease that affects lungs and digestive system)
• Autoimmune blistering dermatosis (blisters and erosions in the skin)
• Diabetes mellitus
• Acute idiopathic dysautonomia (conditions affecting the autonomic nervous system)
• Acute disseminated encephalomyelitis (inflammation in the brain and spinal cord)
• Endotoxemia (toxins in the blood)
• Hemolytic transfusion reaction (blood transfusion reaction in which donor red cells are destroyed by the immune system)
• Hemophagocytic syndrome (immune disorder causing severe inflammation and destruction of all types of blood cells)
• Acute lymphoblastic leukemia
• Lower motor neuron syndrome (loss of reflexes, muscle atrophy and weakness)
• Multiple myeloma
• Human T-cell lymphotropic virus-1–associated myelopathy
• Nephritic syndrome (kidney inflammation)
• Membranous nephropathy (immune disorder in which the immune cells attack the kidney’s filtering membranes)
• Nephrotic syndrome (damage to small blood vessels in the kidney)
• Euthyroid ophthalmopathy (thyroid-related eye disease)
• Opsoclonus-myoclonus (inflammatory nerve disorder that causes involuntary eye movements and muscle jerks)
• Recurrent otitis media (middle ear infection)
• Paraneoplastic cerebellar degeneration (rare condition of brain cell damage related to certain cancers)
• Paraproteinemic neuropathy (neuropathy caused by excessive presence of a single type of immunoglobulin in the blood serum)
• Parvovirus infection
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome (multi-systemic plasma cell disorder)
• Progressive lumbosacral plexopathy (nerve damage in the lumbosacral plexus which controls the thigh and leg muscles)
• Lyme radiculoneuritis (spinal nerve root inflammation caused by Lyme disease)
• Rasmussen syndrome (inflammation of one cerebral hemisphere causing seizures and brain atrophy)
• Reiter syndrome (reactive arthritis from certain infections)
• Acute kidney failure
• Thrombocytopenia (nonimmune)
• Streptococcal toxic shock syndrome
• Uveitis (eye inflammation)
• Vogt-Koyanagi-Harada syndrome (autoimmune inflammatory disorder that affects multiple systems)

Other conditions for which intravenous immunoglobulin therapy has been useful include:

• Clarkson’s disease: Systemic capillary leak syndrome in which excessive plasma leaks out of capillaries into the tissues.
• Scleromyxedema: Thickening and hardening of connective tissue
• Pyoderma gangrenosum: Large painful sores on the skin
• Type II adult-onset pityriasis rubra pilaris: Skin disorder that causes inflammation and scaling of skin
• Febrile ulceronecrotic pityriasis lichenoides: A rare form of pityriasis lichenoides, a skin disorder that causes scaling, raised skin spots.
• Churg-Strauss syndrome-related peripheral polyneuropathy: An inflammatory blood disorder that causes neuropathy
• Pretibial myxedema: Thyroid-related skin disorder
• Ataxic sensory neuronopathy: loss of coordination from nerve damage in brain and spine due to Sjogren’s and stiff man syndromes
• Chronic idiopathic pericarditis: Inflammation of pericardium, the membrane enclosing the heart
• Dilated cardiomyopathy: Enlarged and weakened left ventricle
• Optic neuritis from multiple sclerosis: Inflammation of optic nerve
• Cataplexy related to narcolepsy: Sudden loss of muscle tone that happens during daytime due to narcolepsy, a sleep disorder
• Livedoid vasculitis: Vascular disorder that causes ulceration of the lower extremities
• Graft-versus-host disease in bone marrow transplants
• Rejections in solid organ transplants
• Mixed connective-tissue disease
• Blistering skin diseases such as:
  • Scleroderma
  • Toxic epidermal necrolysis
  • Epidermolysis bullosa acquisita
  • Herpes gestationis
  • Erythema multiforme
  • Chronic autoimmune urticaria
  • Pemphigus foliaceus
  • Mucous membrane pemphigoid