Intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a proposed treatment for chronic fatigue syndrome.

Evidence

There has been inconsistent evidence for the use of IVIG in the treatment of ME or CFS. This may be due to the heterogeneity of triggers and immune system involvement in the ME/CFS population.

The American Journal of Medicine published two studies with different conclusions following each other in the November 1990 issue. The two studies were done in different countries and neither report the case definitions used to identify patients. The study with positive results used a dose twice that as the study with negative results. Following are the abstracts.

Notable studies related to ME/CFS

Positive results

• 1990, A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Done by the Department of Infectious Diseases, Prince Henry Hospital, Sydney, Australia. This study found that a low CD4 count at baseline before IVIG treatment commenced was a predictor of which ME/CFS patients would do well on IVIG.
• 1992, Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome
• 1997, Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents
• 1999, Five-Year Follow-Up of Young People with Chronic Fatigue Syndrome Following the Double Blind Randomised Controlled Intravenous Gammaglobulin Trial
• 2003, Successful Intravenous Immunoglobulin Therapy in 3 Cases of Parvovirus B19-Associated Chronic Fatigue Syndrome
• 2008, Tae Park, MD, presented his study about IVIG for ME/CFS patients at the 3rd Invest in ME International ME Conference. He checked the Glomerular filtration rate (GFR) in 125 ME/CFS patients who met the Fukuda criteria by measuring s-creatinine clearance with cockcroft-auld formula. "We found there were significant renal blood flow improvements in 60 patients (50%) with IVIG treatment...the improvement of renal blood flow is between 35% and 60% of previous GFR. These findings of improved renal blood flow may be evidence of improved cerebral blood flow...[and] may explain the improvement of cognitive function and other symptoms of ME/CFS patients with IVIG treatments."
• 2021, Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - (Full text)

Negative results

• 1990, A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Done by the Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
• 1997, Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome
• 2015, Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome, Attard, Luciano et al.Journal of Clinical Virology , Volume 62 , 54 - 57

Clinicians

Dr. Irving Spurr of the UK, "uses immunogloulin treatment extensively and has not done a RCT [randomized controlled trial] because he does not believe it is ethical to not offer it to clients. There are apparently problems with the use of IVIG in the UK and so he used IM."

Dr. John Chia of the US, uses IVIG in patients with both hypogammaglobulinemia and CFS.

Risks & safety

The risks of IGIV administration must be carefully weighed against potential benefits.

From 1-15% of people receiving IVIG infusions report mild self-limited symptoms, including: fever, chills, headache, myalgia, nausea and/or vomiting, low back pain, increased heart rate, blood pressure changes, shortness of breath and chest tightness. Onset of symptoms range from 30 minutes to several days post-infusion. The cause is thought to be from pathogen die-off and/or a mild allergic reaction. As with any blood product, severe and even fatal anaphylactoid reactions may occur. When using IVIG, the risk is in patients with anti-IgA antibodies of the IgG and IgE isotypes in the patient's serum, though this condition is extremely rare.

Reports of renal failure associated with IVIG occur in less than 1% of cases. Caution is urged for those patients with pre-existing renal insufficiency.

One case study recorded a paradoxical effect where IVIG administration increased the replication of Parvovirus B19, a pathogen associated with CFS.

Costs & availability

IVIG for ME/CFS is considered an off-use or non-FDA approved treatment. As a result, few physicians prescribe it and insurance companies will not cover it, unless a co-morbid condition that merits IVIG exists. The estimated out of pocket cost in the U.S. for a four dose course of IVIG for a 70 kg/155 lb person at 2 g/kg could cost $25,000-$26,000.

See antibody.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

See chronic fatigue syndrome.

See myalgic encephalomyelitis.

double blinded trial A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias. (Learn more: www.nottingham.ac.uk)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

involving, related to or in the area of the kidneys

renal involving, related to or in the area of the kidneys

(CBF) - the amount of blood that goes through the arterial tree in the brain in a given amount of time

cerebral blood flow (CBF) - the amount of blood that goes through the arterial tree in the brain in a given amount of time

cognition Thought processes, including attention, reasoning, and memory.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

See randomized controlled trial.

randomized controlled trial (RCT) - A trial in which participants are randomly assigned to two groups, with one group receiving the treatment being studied and a control or comparison group receiving a sham treatment, placebo, or comparison treatment.

(HR) - the number of times the heart beats within a certain time period, usually a minute

heart rate (HR) - the number of times the heart beats within a certain time period, usually a minute

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)