CFS is increasingly recognised as a heterogeneous condition
07 October 2009
Tom Kindlon
Information Officer (voluntary position)
Irish ME/CFS Association, Dublin, Ireland
Following on from my last e-letter[1]: I have now located the first edition of these guidelines[2]. This edition by Provan et al[2], when putting Chronic Fatigue Syndrome (CFS) in the "black indications" group, explicitly recommends CBT for CFS. This seems to ignore the fact that CFS is increasingly recognised as being a heterogeneous condition[3]. Also, Price et al. [4] reviewed 15 studies of CBT with a total of 1043 ME/CFS participants. At treatment end, 40% of people in the CBT group showed clinical improvement in contrast to only 26% in usual care, but changes were not maintained at a 1-7-month follow-up when including people who had dropped out, which hardly suggests CBT is a solution for all. Roberts et al[5] recently found that the subgroup of CFS with hypocortisolism had a poor response to CBT.
How many of the "eminent neurologists" that Provan et al. refer to had actually used on IVIg on CFS patients? If any have used it, did it help none of their patients? If none were helped, this would seem to be an unusual group from patients I've heard from. Did the "eminent neurologists" make any attempt to sub-group the patients? From what I have heard, most neurologists in the UK are not that interested in CFS so I feel these are valid points to raise.
At the main international conference for CFS, a poster demonstrated that in South Korean CFS patients IVIg improved kidney function[6]. The same researcher also reported a positive outcome for cognitive function. These are outcome measures that have not generally been used in trials of CBT for CFS.
Was the following study[7] looked at: "Antibodies against Epstein- Barr virus, associated with antibody dependent cytotoxic cell activity, were found to be present in diminished titer in 20 of 22 patients tested with chronic mononucleosis syndrome (CMS). Gamma globulin was shown to improve symptoms in 53% of the patients treated, compared with 32% of placebo injections. 89.5% of 57 patients treated with a gamma globulin treatment program remained in the treatment program because of relief of symptoms, and only four patients dropped out because there was no relief of symptoms or side effects. Four patients experienced complete relief of symptoms following a variable length treatment program. It would appear that intramuscular gamma globulin treatment is efficacious in the treatment of CMS and that the average interval between treatments is three weeks." "Chronic mononucleosis syndrome" would generally be called CFS these days.
I have just been reading the minutes of the last (US) Chronic Fatigue Syndrome Advisory Committee (CFSAC) meeting[8]. The CFSAC is a federal US committee which advises the Health and Human Services Secretary on matters relating to CFS. Dr. James Oleske, chairman of the committee mentioned his experiences of IVIg:
"I got involved with CFS mainly because I was studying very severe EBV patients and post-EBV people who were having some clear and defined immunodeficiencies. I was involved in a clinical trial to see if IV gammoglobulin helped them. The data I have is on a much more infectious disease-driven group than Dr. Jason's."
[..]
"There are a number of investigational therapies that I don't think we've done much with because we haven't had a clinical trial program where we can enroll patients from multiple sites. The numbers game becomes very important. I can tell you that immunoglobulin helps patients who have subclass deficiency and recurring pulmonary infections"
[..]
"I also had analyzed the kids on gammaglobulin. I can't publish this data because when I submitted it, most of the people said, "What are your criteria for diagnosis?"
I thought I would also mention this successful double-blind, placebo- controlled trial[9] which had the following results and conclusions: "RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each). CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder."
In my last reply[1], I included information on the successful trial by Kerr and colleagues[10] on the CFS subgroup associated with Parvovirus B-19. A case-study[11] also found IVIg to be successful for a case of CFS associated with Parvovirus B19.
Given this information, I hope for the next edition of the guidelines, serious consideration will be given as to whether it would be better to put CFS in the grey indications group, rather than the black indications group. ["Grey indications are those for which the evidence base is weak, in many cases because the disease is rare; IVIg treatment should be considered on a case-by-case basis, prioritised against other competing demands." Black indications: "Indications for which IVIg is not recommended - The prescription of IVIg is not appropriate for the following conditions."]
References:
[1] Kindlon T. On what basis was it decided that Immunoglobulin was not suitable for CFS?
http://www.bmj.com/cgi/eletters/337/oct20_2/a1831#203678
[2] Provan D et al. Clinical guidelines for the use of intravenous immunoglobulin. (1st edition)
http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/di... [Last accessed: 2 Oct 2009]
[3] Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C. Chronic fatigue syndrome: the need for subtypes. Neuropsychol Rev. 2005 Mar;15(1):29-58. Review. PMID: 15929497
[4] Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database of Systematic Reviews Issue 2. Art No.: CD001027. doi:10.1002/14651858. CD001027.pub2.
[5] Roberts AD, Charler ML, Papadopoulos A, Wessely S, Chalder T, Cleare AJ. Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome? Psychol Med. 2009 Jul 17:1-8. [Epub ahead of print] PMID: 19607750
[6] Park T. Improved renal function in CFS patients with IV immunoglobulin treatment. Poster Presentation, 9th International IACFS/ME Research and Clinical Conference, March 2009.
[7] Dubois RE. Gamma globulin therapy for chronic mononucleosis syndrome. AIDS Research 1986; 2(1): 191-5.
[8] Minutes of the CFSAC Meeting, May 2009. US Dept of Health & Human Services website:
http://www.hhs.gov/advcomcfs/meetings/minutes/cfsac052709min.pdf [Last accessed: 2 Oct 2009]
[9] Lloyd A, Hickie I, Wakefield D, Boughton CR. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. American Journal of Medicine 1990; 89: 561-68.
[10] Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN. Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19 -associated chronic fatigue syndrome. Clin Infect Dis. 2003 May 1;36(9):e100-6
[11] Jacobson SK, Daly JS, Thorne GM, McIntosh K. Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case history and review. Clin Infect Dis. 1997 Jun;24(6):1048-51.
Competing interests: None declared
Competing interests: No competing interests
