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Intravenous immunoglobulin
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'''Intravenous immunoglobulin''' (IVIG) is a proposed treatment for [[chronic fatigue syndrome]]. ==Theory== ==Evidence== There has been inconsistent evidence for the use of IVIG in the treatment of [[myalgic encephalomyelitis|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.<ref name="lloyd1990" /> *1992, Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome<ref name="Hickie, 1992"/> *1997, Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents<ref name="Rowe, K, 1997"/> *1999, Five-Year Follow-Up of Young People with Chronic Fatigue Syndrome Following the Double Blind Randomised Controlled Intravenous Gammaglobulin Trial<ref name="Rowe, K, 1999"/> *2003, Successful Intravenous Immunoglobulin Therapy in 3 Cases of Parvovirus B19-Associated Chronic Fatigue Syndrome<ref name="Kerr, 2003"/> *2008, [[Tae Park]], MD, presented his study about IVIG for ME/CFS patients at the [http://www.investinme.org/IIMEC3.shtml#report 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."<ref name="iime2008" /> * 2021, Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Brownlie2021">{{Cite journal | title = Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2021-11-12 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623195|journal=Healthcare|volume=9|issue=11|pages=1546 | last = Brownlie | first = Helen | authorlink = | last2 = Speight | first2 = Nigel | authorlink2 = Nigel Speight|doi=10.3390/healthcare9111546|pmc=PMC8623195|pmid=34828592|access-date=|issn=2227-9032|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623195 (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.<ref name="peterson1990" /> *1997, Intravenous immunoglobulin is ineffective in the treatment of patients with [[chronic fatigue syndrome]]<ref>{{Cite journal | last = Vollmer-Conna | first = U | author-link = UtΓ© Vollmer-Conna | last2 = Hickie | first2 = I | last3 = Hadzi-Pavlovic | first3 = D | last4 = Tymms | first4 = K | last5 = Wakefield | first5 = D | last6 = Dwyer | first6 = J | last7 = Lloyd | first7 = A | authorlink7 = Andrew Lloyd | date = 1997 | title = Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome | url = http://dx.doi.org/10.1016/S0002-9343(97)90045-0|journal=American Journal of Medicine|volume=103|pages = 38-43 |doi=10.1016/S0002-9343(97)90045-0|via=}}</ref> *2015, [http://www.journalofclinicalvirology.com/article/S1386-6532(14)00447-8/abstract 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."<ref name="iime2008" /> Dr. [[John Chia]] of the US, uses IVIG in patients with both hypogammaglobulinemia and CFS.<ref>[https://med.stanford.edu/chronicfatiguesyndrome/infections/entero/entero-treatment.html Stanford ME/CFS Initiative β Enteroviruses Treatment Options β Physician Perspective: John Chia, MD]</ref> ==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.<ref name="duhem1994" /><ref>[https://primaryimmune.org/wp-content/uploads/2011/11/Work-Group-Report-III.pdf American Academy of Allergy, Asthma & Immunology β Work Group Report on the appropriate use of intravenously administered immunoglobulin (IGIV)] (pdf)</ref> 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.<ref name="ahsan1998" /> One case study recorded a paradoxical effect where IVIG administration increased the replication of [[Parvovirus B19]], a pathogen associated with CFS.<ref name="attard2015" /> ==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.<ref>http://www.medscape.com/viewarticle/523523_5</ref> ==See also== ==Learn more== ==References== <references> <ref name="Hickie, 1992"> {{Cite journal | last1 = Hickie | first1 = I. | authorlink1 = Ian Hickie | last2 = Lloyd | first2 = A. | authorlink2 = Andrew Lloyd | last3 = Wakefield | first3 =D. | authorlink3 = | title = Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome. | journal = The Australian and New Zealand Journal of Psychiatry | volume = 26 | issue = 2 | pages = 249-56 | date = June 1992 | pmid = 1642616 | url = http://www.ncbi.nlm.nih.gov/pubmed/1642616 }}</ref> <ref name="Rowe, K, 1997"> {{Cite journal | last1 = Rowe | first1 = K.S. | authorlink1 = Kathy Rowe | title = Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. | journal = Journal of Psychiatric Research | volume = 31 | issue = 1 | pages = 133-47 | date = 1997 | pmid = 9201655}}</ref> <ref name="Rowe, K, 1999"> {{Cite journal | last1 = Rowe | first1 = K.S. | authorlink1 = Kathy Rowe | title = Five-Year Follow-Up of Young People with Chronic Fatigue Syndrome Following the Double Blind Randomised Controlled Intravenous Gammaglobulin Trial | journal = Journal of Chronic Fatigue Syndrome | volume = 5 | issue = 3-4 | pages = 97-107 | date = 1999 | doi = 10.1300/J092v05n03_08}}</ref> <ref name="Kerr, 2003"> {{Cite journal | last1 = Kerr | first1 = J. R. | authorlink = Jonathan Kerr | last2 = Cunniffe | first2 = V. S. | authorlink2 = | last3 = Kelleher | first3 = P. | authorlink3 = | last4 =Bernstein | first4 = R.M. | authorlink4 = | last5 = Bruce | first5 = I. N. | authorlink5 = | title = Successful Intravenous Immunoglobulin Therapy in 3 Cases of Parvovirus B19-Associated Chronic Fatigue Syndrome | journal = Clinical Infectious Diseases | volume = 36 | issue = 9 | pages = 100-106 | date = 2003 | doi = 10.1086/374666 }}</ref> <ref name="attard2015">{{Cite journal | doi = 10.1016/j.jcv.2014.11.021| issn = 1386-6532| volume = 62| pages = 54β57| last1 = Attard | first1 = Luciano | last2 = Bonvicini | first2 = Francesca | last3 = Gelsomino | first3 = Francesco | last4 = Manfredi | first4 = Roberto | last5 = Cascavilla | first5 = Alessandra | last6 = Viale | first6 = Pierluigi | last7 = Varani | first7 = Stefania | last8 = Gallinella | first8 = Giorgio| title = Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome| journal = Journal of Clinical Virology| access-date = 2016-12-12 | date = 2015-01-01| url = http://www.journalofclinicalvirology.com/article/S1386-6532(14)00447-8/abstract| pmid = 25542471}}</ref> <ref name="ahsan1998">{{Cite journal | issn = 1121-8428| volume = 11 | issue = 3| pages = 157β161| last = Ahsan | first = N.| title = Intravenous immunoglobulin induced-nephropathy: a complication of IVIG therapy| journal = Journal of Nephrology | date = June 1998 | pmid = 9650125}}</ref> <ref name="duhem1994">{{Cite journal | issn = 0009-9104| volume = 97 | issue = Suppl 1| pages = 79β83| last1 = Duhem | first1 = C| last2 = Dicato | first2 = M A| last3 = Ries | first3 = F| title = Side-effects of intravenous immune globulins.| journal = Clinical and Experimental Immunology| access-date = 2016-12-12 | date = July 1994| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550378/| pmid = 8033440}}</ref> <ref name="peterson1990">{{Cite journal | issn = 0002-9343| volume = 89 | issue = 5| pages = 554β560| last1 = Peterson | first1 = P.K. | last2 = Shepard | first2 = J. | last3 = Macres | first3 = M. | last4 = Schenck | first4 = C. | last5 = Crosson | first5 = J. | last6 = Rechtman | first6 =D. | last7 = Lurie | first7 = N.| title = A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome| journal = The American Journal of Medicine | date = November 1990 | pmid = 2239975}}</ref> <ref name="lloyd1990">{{Cite journal | issn = 0002-9343| volume = 89 | issue = 5| pages = 561β568| last1 = Lloyd | first1 = A. | authorlink1 = Andrew Lloyd | last2 = Hickie | first2 = I. | authorlink2 = Ian Hickie | last3 = Wakefield | first3 =D. | last4 = Boughton | first4 = C. | last5 = Dwyer | first5 = J.| title = A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome| journal = The American Journal of Medicine | date = November 1990 | pmid = 2146875}}</ref> <ref name="iime2008">{{Cite web |url = http://www.investinme.org/IIMEC3.shtml#report | title = 3rd Invest in ME International ME Conference 2008 β Report | last = Baken | first = Don|website =Invest in ME Research |access-date=2022-01-16}}</ref> </references> [[Category:Potential treatments]] [[Category:Immunomodulators]] [[Category:Antibodies]] [[Category:Immunology]] [[Category:Biochemistry and cell biology]] [[Category:Glycoproteins]]
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