Does anyone remember CFIDS, aka Chronic Fatigue and Immune Dysfunction Syndrome? Back in the 1990s this was the accepted term for what is now called CFS, or, if you are so inclined, ME/CFS. The “ID” was quietly dropped by researchers and doctors about 10 years ago in favor of Steven Straus’s infamous legacy: chronic fatigue syndrome. Everyone agrees that CFS is a confusing, misleading and utterly dismissive name for the illness. Not only does it harm the people who have CFS, it harms the people who don’t. In a recent study of patients newly diagnosed with MS, nearly one-third had been diagnosed with CFS (or with the even more vague, “fatigue”) for one to two years prior to being diagnosed with MS.
Imagine how many other patients with incipient cancer, heart disease, liver disease, diabetes (to name a few “fatiguing” illnesses) have had the catch-all diagnosis of CFS slapped on them simply because they were tired. The term CFS has been just as much a curse to those patients, whose correct diagnoses and treatments have been delayed by years, as it has been to patients with CFIDS.
Who did this? Who managed to drop the all-important feature of immune dysfunction from the name? After all, it is obvious that people with CFIDS have an immune dysfunction. Chronicity is, in fact, the product of an altered immune system. With a fully functioning immune system, the host recovers. Immune dysfunction is not just a feature of chronic disease, it is its definition.
What’s more, the furor over what to call the “Disease of a Thousand Names” has only intensified since the “ID” dropped out. Prior to its deletion, people who had been diagnosed with (depending on their geographic location) ME (myalgic encephalomyelitis) or CFIDS maintained a cordial relationship. Since the change, they are at each other’s throats. People with ME do not want to be diagnosed with an illness that not only reduces all their symptoms to the “f” word, but is doggedly lumped into some ill-defined category of mental illness.
Who did this? Who managed to divide what was once a unified community into squabbling sororities? The CFIDS community could, and did, accomplish so much when it spoke with one voice: national organizations, political lobbies, well-subscribed magazines. Now, it is factionalized, torn apart by the desire to achieve maximum distance from the stigma of “fatigue.”
An even more disturbing consequence of dropping the “ID” is that supposed friends, clinicians who once championed the cause, have not only slipped into the term CFS, but are adding insult to injury by dropping the S part and referring to an illness which not only destroys lives, but can eradicate them, simply as “chronic fatigue.” It’s bad enough when patients call their illness “chronic fatigue,” but Nancy Klimas, head of the Neuro Immune Institute and world-renowned CFIDS specialist, should know better.
Who did this? Who trivialized this illness among formerly committed researchers and clinicians? Who robbed CFIDS patients of their defenders?
In 2002, Benjamin Natelson, noted CFIDS researcher, was given a grant by the NIH to do a meta-analysis of immune studies in CFIDS patients. Meta-analyses are not research studies, they are merely analyses of studies that have been performed in the past. Because meta-analyses basically serve as CliffsNotes for researchers who are too pressed for time to read the original work, their ultimate value to the research community has been questioned.
Natelson’s meta-analysis, entitled “Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome,” examined 79 studies of immune function in CFIDS patients. Natelson found that that there was no consistent immune dysfunction. Some studies indicated that there were increased pro-inflammatory cytokines, others found increased anti-inflammatory cytokines.
Given the fact that one of the hallmarks of CFIDS is waxing and waning symptoms, this should not have come as a surprise. The immune dysfunction that characterizes CFIDS is that it both under- and over-responds. This is the ultimate outcome of the loss of homeostasis which lies at the heart of the illness.
Natelson ignored this aspect of immune dysfunction, just as he ignored the one consistent piece of data he found across these studies: low natural killer (NK) cell function. He concluded that “the available evidence does not support chronic fatigue syndrome as being due to any consistent immunological dysfunction […] we believe that the term “chronic fatigue syndrome” is preferable to the older “chronic fatigue and immune dysfunction syndrome.”
Aside from the damaging consequences of this conclusion, it turns out that Natelson was wrong.
In 2012, a group of Australian researchers headed by Ekua Brenu completed the first longitudinal study of immune function in patients with CFS/ME (CFIDS). This was the first time researchers had examined immune function over a long period of time, in this case, 12 months. The value of longitudinal studies to measure immune function is that the immune system is a moving target. It responds instantly to environmental input. Even the best short-term study of the immune system can’t give researchers more than a snapshot.
The Brenu study found that patients with CFIDS do indeed have an immune system dysfunction. It is the same immune dysfunction that most other immune studies have found over the past two decades: low NK function. The natural killer cells of CFIDS patients ignore invaders, tumor cells among them (which is perhaps why so many people diagnosed with CFIDS in the 1980s went on to develop lymphomas). The authors concluded that because cytotoxic activity was consistently decreased during the course of the 12-month study it “may be a suitable biomarker for diagnosing CFS/ME.”
Notwithstanding the tantalizing possibility that a biomarker may have finally been found, the real clincher came at the end of the discussion section, where the authors explained why previous short-term studies had been equivocal:
“Cytokine release in CFS/ME patients undergoes shifts during the course of the disease where patients may present with either an amplified or depressed anti-inflammatory or pro-inflammatory cytokine profile. These alterations in cytokine secretion may occur during the course of the disease and at different times causing either a shift towards a predominant Th1 or Th2 immune response in CFS/ME This makes it difficult to establish a unique CFS/ME-like inflammatory cytokine profile. The observed pattern of cytokine distribution among our CFS/ME patients is consistent with equivocal findings in the literature. In adolescents with CFS/ME, cytokine secretions have been observed to be correlated with seasonal variations. Therefore, CFS/ME may be associated with oscillations in pro and anti-inflammatory cytokines, supporting the heterogeneity and multifactorial nature of the disease and the diversity in symptom presentations.”
That paragraph alone should have heralded a new age in CFIDS research. It should have stimulated a lively discussion. It should have prompted a retraction of Natelson’s damning conclusion. It should have reinserted the ID.
But instead of doing any of those things, it was ignored, not just by the broader scientific community, but by CFIDS researchers, clinicians and, saddest of all, by those who would have benefitted the most – the patients. We are now lying in the bed that has been made for us.
And it is a hard one.
Berger JR, Pocoski J, Preblick R, Boklage S. “Fatigue Heralding Multiple Sclerosis,” Mult Scler. 2013 Feb 25. [Epub ahead of print].
Natelson, Benjamin H., Mohammad H. Haghighi, and Nicholas M. Ponzio. “Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome.” Clin Diagn Lab Immunol. 2002 July; 9(4): 747–752.
Ekua W Brenu, Mieke L van Driel, Donald R Staines, Kevin J Ashton, Sharni L Hardcastle, James Keane, Lotti Tajouri, Daniel Peterson, Sandra B Ramos, and Sonya M Marshall-Gradisnik. “Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis.” J Transl Med 2012; 10: 88 doi: 10.1186/1479-5876-10-88.