The Holmes definition, published in 1988 for “research purposes,” is also known as the CDC 1988 criteria. It was the first official definition of chronic fatigue syndrome (CFS) used by the US Centers for Disease Control and Prevention (CDC). The CDC later adopted the 1994 Fukuda criteria for CFS then the 2015 IOM criteria for ME/CFS.
The term CFS was used to replace a “popular” term used mostly in mid to late 1980s – Chronic Epstein-Barr virus (EBV) syndrome – largely because research found no consistent link between EBV and the defined symptoms, and that whilst one study suggested associations with EBV, the authors noted that other viruses – such as cytomegalovirus, herpes simplex virus, and measles virus – had equal or stronger associations. Thus, the authors proposed a name – CFS – that according to them described “the most striking clinical characteristic of the chronic Epstein-Barr virus syndrome” – fatigue – “without implying a causal relationship with” EBV.
The paper stated that “physicians must recognize [CFS] not necessarily as a single disease but as a syndrome—a complex of potentially related symptoms that tend to occur together—that may have several causes.” It seems the authors did not predict the controversy that would occur as a result of including fatigue within the name, including the fact that many would simplify the syndrome to simply that one feature (and further mischaracterise it as just tiredness) despite this not being the original intent of the publication.
Summary of Holmes Definition
To be diagnosed with CFS, a patient must meet all major criteria. For minor criteria, the patient must meet 6 or more of the symptom criteria and 2 or more of the physical criteria, OR 8 or more of the symptom criteria.
Major criteria
Mandatory for diagnosis:
- Fatigue – “New onset of persistent or relapsing, debilitating fatigue or easy fatigability in a person who has no previous history of similar symptoms, that does not resolve with bedrest, and that is severe enough to reduce or impair average daily activity below 50% of the patient’s premorbid activity level for a period of at least 6 months.”
- Exclusion of other similar clinical conditions by thorough evaluation. Some examples included – malignancy, chronic or subacute bacterial disease (e.g. Lyme disease), chronic psychiatric disease (e.g. “endogenous depression)
Minor Criteria
Symptom criteria
“To fulfill a symptom criterion, a symptom must have begun at or after the time of onset of increased fatigability, and must have persisted or recurred over a period of at least 6 months (individual symptoms may or may not have occurred simultaneously)”
- Mild fever (oral temperature 37.5° C – 38.6° C) or chills
- Sore throat
- Painful cervical or axillary lymph nodes
- Unexplained generalised muscle weakness
- Muscle discomfort or pain (myalgia)
- “Prolonged (24 hours or greater) generalized fatigue after levels of exercise that would have been easily tolerated in the patient’s premorbid state.”
- Generalised headaches (different type, severity, or pattern to premorbid state)
- Migratory joint pain (without swelling or redness)
- “Neuropsychologic complaints (one or more of the following: photophobia, transient visual scotomata, forgetfulness, excessive irritability, confusion, difficulty thinking, inability to concentrate, depression).”
- Sleep disturbance (hypersomnia or insomnia)
- “Description of the main symptom complex as initially developing over a few hours to a few days (this is not a true symptom, but may be considered as equivalent to the above symptoms in meeting the requirements of the case definition).”
Physical Criteria
“Must be documented by a physician on at least two occasions, at least 1 month apart.”
- Low-grade fever (oral 37.5° C – 38.6° C, or rectal 37.8° C – 38.8° C)
- Nonexudative pharyngitis (inflammation of back of throat without pus)
- Palpable or tender cervical or axillary lymph nodes (anterior or posterior)
Critique and considerations
Terminology:
Chronic fatigue syndrome as a standalone term is problematic because it is often shortened to chronic fatigue or people overlook the definition of a syndrome. This leads to a disproportionate on fatigue, which many healthy individuals do not look at differently from common tiredness or exhaustion that can be alleviated by rest, thus resulting in invalidation of lived experience.
Bristol’s NHS web article [accessed Aug 2025] explains why the NHS combined the term ME with CFS – “The short answer is that they are the same. M.E. was first used in the UK, and CFS was first used in the USA, and both terms have been used to describe the same problem. The NHS has for many years used the combined term “CFS/ME” and is moving towards using the term “ME/CFS”…”
Post-Exertional Malaise:
Whilst the term post-exertional malaise (PEM), considered to be the hallmark feature of ME/CFS, is not stated explicitly in the criteria, the phrase “Prolonged (24 hours or greater) generalized fatigue after levels of exercise that would have been easily tolerated in the patient’s premorbid state” seems to partially describe it. Nevertheless, similar to the Fukuda criteria, as it is not mandatory for diagnosis, it is possible to be diagnosed with CFS without the presence of this symptom.
Psychiatric exclusions:
One criticism of the Holmes criteria is its approach to psychiatric conditions – “Although chronic psychiatric disease is listed as an excluding condition, it did not rule out all psychiatric conditions. For example, the criteria specifically listed ‘endogenous depression,’ which is a term used to describe depression which is caused by the patients’ physiology, such as a major depressive disorder or bipolar disorder. However, it did not exclude ‘exogenous depression,’ which is a term used to describe depression precipitated by a life-altering event such as grief or loss.”
In a year 2000 editorial, Dr Anthony Komaroff, who was involved in both the Holmes and Fukuda definitions, stated: “Some of us who study the syndrome suspect that it can be triggered, in susceptible patients, by chronic infection with any of several agents that are difficult or impossible to eradicate… Furthermore, the report is inconsistent with the hypothesis that chronic fatigue syndrome involves symptoms that are only imagined or amplified because of underlying psychiatric distress—symptoms that have no biological basis. It is time to put that hypothesis to rest and to pursue biological clues … ”
CDC’s relations with ME community:
A 2017 blog post critiqued the CDC’s approach towards the ME community over the years, stating “Dr. Lee, the previous DFO of CFSAC, stated at one of their meetings – ‘it is not the job of the government to create definitions for diseases, it has to come from the community of experts.’ Yet, since the 1980’s the CDC has perpetually ignored the name and criteria authored by experts and has produced one faulty definition after another (Holmes, Fukuda, Fukuda, and IOM).”
Reference:
Holmes, G.P., Kaplan, J.E., Gantz, N.M. and Pahwa, S. (1988). Chronic Fatigue Syndrome: A working case definition. Annals of Internal Medicine, [online] 108(3), pp.387–9. [Accessed 1 Sep. 2025].
