Off-Label Uses for Intravenous Immunoglobulin Therapy

Intravenous immunoglobulin therapy boosts a patient’s immune response, making it a valuable treatment option when other methods fail.

Intravenous immunoglobulin (IVIG) therapy treats individuals with compromised immune systems caused by genetic disorders or acquired diseases. Immunoglobulins are blood antibodies that defend against infections.

IVIG preparations, derived from pooled plasma from over 1,000 healthy donors, are purified before administration. These preparations consist primarily of IgG, a naturally occurring immunoglobulin in humans, unaffected by immunization or antigen exposure.

Typically, IVIG infusions are administered every three or four weeks.

How does IVIG work?

IVIG therapy operates in two opposing ways:

• Suppresses the immune system in patients with:
• Autoimmune disorders
• Solid organ or bone marrow transplants

What is IVIG used for?

FDA-approved uses for IVIG include treating the following immune-related disorders:

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

What are the off-label uses for IVIG therapy?

In addition to FDA-approved conditions, IVIG is utilized in the treatment of various autoimmune and infectious diseases, as well as conditions with unknown causes.

According to the National Guideline Clearinghouse, off-label IVIG uses 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 blisteringdermatosis (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 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 causing 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 immunoglobulin type in 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 lumbosacral plexus controlling 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 affecting multiple systems)

Intravenous immunoglobulin therapy has also proved effective in treating other conditions, including:

• Clarkson’s disease: Systemic capillary leak syndrome characterized by excessive plasma leakage from capillaries into 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 causing inflammation and scaling
• Febrile ulceronecrotic pityriasis lichenoides: Rare form of pityriasis lichenoides, a skin disorder causing scaling and raised skin spots
• Churg-Strauss syndrome-related peripheral polyneuropathy: Inflammatory blood disorder causing neuropathy
• Pretibial myxedema: Thyroid-related skin disorder
• Ataxic sensory neuronopathy: Coordination loss resulting from nerve damage in the 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 during daytime due to narcolepsy, a sleep disorder
• Livedoid vasculitis: Vascular disorder causing 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 like:
• Scleroderma
• Toxic epidermal necrolysis
• Epidermolysis bullosa acquisita
• Herpes gestationis
• Erythema multiforme
• Chronic autoimmune urticaria
• Pemphigus foliaceus
• Mucous membrane pemphigoid