Pinpointing chronic fatigue
Two decades after chronic fatigue syndrome was defined, the illness continues to baffle doctors and wreak havoc on patients’ lives. Rosemarie Milsom looks at some of the theories behind the origin of the condition.
THEDA Myint’s list of symptoms is as long as it is debilitating: crippling exhaustion; intense, constant head pain; severe fibromyalgia partially controlled by tramadol; extreme sensitivity to light, sound and touch; food and inhalant allergies; gastrointestinal problems; migraines; dizziness; poor memory and concentration; and hormone imbalances.
The 34-year-old spends most of her days bedridden in a darkened room, being cared for by her mother in their Perth home.
Her illness began a decade ago when she contracted influenza while travelling in the UK. She never bounced back and was diagnosed with myalgic encephalomyelitis – better known as chronic fatigue syndrome (CFS) – a few years later.
Ms Myint is too sick to participate in an interview, but her partner, Blake Graham, describes the devastating impact CFS has had on her life.
“Theda has had to give up virtually everything,” he says. “She can’t see her friends, she lives in severe physical pain and is incredibly bored. She is unable to do anything other than listen to book tapes in the dark.”
Ms Myint has received numerous conventional treatments for CFS, including psychiatric, sleep and pain medication, cognitive behavioural therapy, graded exercise therapy, transcranial magnetic stimulation and counselling. Non-traditional treatment has included hormone therapy, oral and IV nutrients, herbs, acupuncture, hyperbaric oxygen therapy, homeopathy and meditation.
Ms Myint’s range of symptoms, while protracted, is not uncommon among the 0.5%–2.5% of Australians diagnosed with CFS, though the variation and severity can differ greatly.1
This is what makes CFS, 22 years after it was first defined by the US Centers for Disease Control and Prevention, one of the most misunderstood and challenging illnesses confronting medicine.
Despite decades of research, there is no clear-cut cause or treatment and no diagnostic test.
“There is no specific treatment, as we do not, as yet, understand the disease mechanisms,” says microbiologist Dr Jonathan Kerr, a consultant at London’s St George’s University who is investigating the involvement of key genes in CFS.
Another significant issue that continues to surround CFS is the ongoing tension between those who believe that the illness is primarily psychological and those who believe it is biological.
Definitions of CFS also vary between countries, making it difficult for both doctors and patients.
“This issue has caused problems in comparing research studies one with another, for obvious reasons,” Dr Kerr says.
“For individual patients too, the fact that there are various definitions has weakened the case for the existence of the syndrome, which further erodes its reputation within the medical profession.”
In Australia, doctors can refer to Clinical Practice Guidelines: Chronic Fatigue Syndrome, which was produced by a working group convened under the auspices of the Royal Australasian College of Physicians and published in the MJA in 2002.2
The guidelines were met with criticism from patient groups for the use of psychological language and the downplaying of biological aspects of CFS. They believed the guidelines skipped too lightly over emerging evidence that metabolic disorders, infections and immunological problems could cause CFS.
“The overall impression is that it’s an illness that’s very much exacerbated or somehow caused by perceptions, by a cognitive problem,” the then president of the ME/CFS Association of Australia, Simon Molesworth, told media.
According to the guidelines, if a person experiences disabling fatigue for longer than six months, and has symptoms like headaches, joint pain, impaired concentration and is not refreshed by sleeping, they should be considered candidates for CFS.
Doctors were urged not to rush into a diagnosis: “When the prognostic features are favourable... a more non-committal diagnosis, such as ‘post-infectious fatigue state’ may be more appropriate.”
Beyond the guidelines, Mr Graham, who is also president of the ME/CFS Society of WA, adds: “There have been over 5000 peer-reviewed articles on ME/CFS published... and while there is still much to learn, there is more information out there than people realise.”
One important work, he says, is Missed Diagnoses: Myalgic Encephalomyelitis & Chronic Fatigue Syndrome by Dr Byron Hyde, a Canadian doctor who heads the Nightingale Research Foundation, 3 which has been investigating the condition since the mid-1980s. The foundation’s extensive definition of the syndrome is also widely supported by sufferers as being the most detailed and precise.
The path to diagnosis isn’t easy, despite guidelines and increased awareness.
“The patient will have to make multiple visits to, typically, several doctors in order to obtain symptomatic management for their problems,” Dr Kerr says.
“These interactions with doctors may be frustrated by the fact that they are not trained to treat this illness – many do not accept its existence.”
A lingering misconception is that CFS is an atypical form of depression, which is not surprising according to Professor Andrew Lloyd, infectious diseases physician at the University of NSW’s school of medical sciences.
“We know that approximately 50% of all patients with CFS, sometime in the course of their illness, will have clinically significant depression. It can be considered reactive – terrible illness, upturns your life, no wonder you’re depressed – but in addition, there’s evidence that it’s a neurochemical disturbance.
“That fits with where the money is about the pathophysiology of chronic fatigue syndrome. If you believe major depression ultimately has a neurochemical basis, it’s not a surprise that patients might develop it as part of the biology of chronic fatigue syndrome.”
Professor Lloyd, who helped write the 2002 clinical guidelines and is a lead researcher for the Dubbo Infection Outcomes Study (DIOS), emphasises that traditional antidepressant medication when prescribed to patients with CFS has little impact, and some people report feeling worse.
There is increasing evidence and acceptance that CFS is a brain disorder that is multifactorial in origin. Studies show that certain infections can be a trigger for the onset of CFS, the best known being Epstein-Barr virus, and the DIOS adds Ross River virus and Q fever.4
“Maybe it’s an aberrant host response, an exaggerated immune response against the initiating infection, and that really it’s a protracted resistant response that’s the driver. I’m pretty confident the persistence of the organism isn’t the driver,” Professor Lloyd says.
Dr Kerr’s research and that of others, including Dr Nancy Klimas from the University of Miami’s department of immunology, have centred on genetics and have found that abnormalities are frequently found in CFS patients:
“For example, abnormal expression of 88 human genes and five microRNAs, DNA mutations, and abnormal perforin levels in natural killer cells,” Dr Kerr says.
In Dr Kerr’s study, 16 genes were abnormal, and although they had varying functions, the number one function was the immune system. CFS might be split into a number of distinct genetic types in the future.5
While research is expanding our understanding of CFS, for now it brings little joy to Theda Myint, though her loved ones are hopeful about further testing and possible treatment options overseas.