Twenty of so years ago, I was invited to go on a lecture tour of Calcutta. This gave me the opportunity to fulfil a lifetime ambition to visit the Himalayas, so I and a few colleagues from Sheffield took the hissing and clanking narrow gauge railway up to the old British hill station of Darjeeling. I remember the thrill of waking up with views on the sun on the slopes of Mount Everest. We started the trek the next day at an altitude of 14,000 feet, but within a mile I hardly had the energy to put one in front of another. I had altitude sickness and spent the next two days unable to move, wrapped up in blankets in front of a dish of glowing charcoal. I had never experienced anything quite like it; even when, some years later, I had malaria, I was not nearly so exhausted. My symptoms cleared up within two days. What must it be like to have such enervating fatigue for years and years, to be so weak that you can hardly do anything, yet to be faced with a climate of disbelief, not only from doctors but also friends and family. This is what people with Myalgic Encephalomyeltitis/Chronic Fatigue Syndrome (ME/CFS) experience.
Yet knowledge about ME/CFS has moved on the last five years. In a recent webinar, Dr Anthony Komoroff, Professor of Medicine at Harvard University, stated that it is no longer just a set of symptoms with no obvious biological determinants; a range of abnormalities have been identified in CFS/ME. They include disturbances in the neuro-endocrine (limbic-hypothalamic-pituitary axis) and autonomic nervous systems, changes in cognition, disturbances in immune function not only in the body but also the brain, and changes in energy metabolism at a cellular level (reduced oxygen consumption and increased lactic acidosis). None of these are specific for ME/CFS; they can occur in other conditions. Furthermore, they do not amount to a coherent cause or disease mechanism and they have not yielded a diagnostic test or any proven effective treatment.
In this, CFS/ME shows a remarkable similarity to IBS, with which there is extensive overlap. IBS is also associated with neuro-endocrine, autonomic and immunological disturbances as well as changes in mood and cognition and alterations in the brain gut axis, but none of these amount to a definitive cause or mechanism. Both conditions are associated with a range of other unexplained symptoms including headaches, faintness, sleep disturbance, muscle pain and joint pain. And like CFS/ME, IBS has no definitive diagnostic test and no specific treatment.
Psychological factors have been implicated in both illnesses, but the biological features in IBS and CFS/ME are not generally found in primary psychiatric disorders such as schizophrenia, autism or major depression. This may suggest that psychological disturbances may be secondary to the biological disturbance; chronic ill health always has a major effect on our emotions and bacterial products can affect mood and fatigue. Alternatively, it could indicate that psychological disturbance perhaps in association with some injury or infection could set in train a longstanding debilitating inflammatory illness through the affective nervous system and the immune and endocrine systems.
This however begs the questions: why does CFS/ME often commence in teenagers and why is it more common in girls? Is it that teenage is a time when children come into contact with wider communities? Does this not only expose them novel infections but also novel and possibly traumatic experience?
Twenty years ago Dr Kok-Ann Gwee and I showed that when a gut infection was associated with anxiety, depression or a traumatic life event, the inflammation and symptoms of the original illness were more likely to continue as post infectious IBS. We said at the time that it was as if the physical symptoms were recruited to express the presumed ongoing stress. The same applied to other infectious illnesses though we found that after a time the symptoms of each tended to coalesce into chronic fatigue. ME/CFS also often starts abruptly with an infectious illness, but the symptoms do not clear up and may last for years, just like post infectious IBS. Several candidates have been proposed as instigators of CFS/ME, including the Epstein-Barr virus in Glandular Fever, the influenza virus, herpes virus and candida albicans. Dr Komaroff suggests that there is not a specific infectious agent, but the important thing might be that the infection is not easily cleared by the immune system.
With appropriate caution, Dr Komaroff said that there was now abundant evidence to indicate that CFS/ME was a long standing inflammatory condition involving disturbances in immunological mediators (cytokines) both in the body and the brain. Cytokines arising from tissue damage or infections may act via the blood stream or afferent nerves to cause all the features of illness behavior. Furthermore he suspected that this condition may arise from a disturbances in the gut microbiome since these have been shown to cause changes in immunological activity and changes in the nervous system. A similar hypothesis has been suggested for IBS.
It is unfortunate that ME/CFS is still seen as too controversial to excite investment from the pharmaceutical industry, despite the existence of anti-inflammatory agents that can permeate the blood-brain barrier, but he nevertheless anticipates a diagnostic test and specific treatment in the next five years.
In the meantime, graded exercise and cognitive behavioural therapy are seen as standard treatment for CFS/ME and are said to improve symptoms in 22 % of patients although this study is highly controversial with patient groups claiming it is unethical. When I was ill in Darjeeling, there was no way I had the energy to engage in exercise or any form of thought or even food. I was just too exhausted.
Do people get over CFS/ME? The literature is unclear, though it does suggest that, like IBS, the symptoms of ME/CFS may go into remission, but there might always be a tendency to relapse. Dr Komaroff suggested that in his experience, it was rare to find anybody who completely recovered from CFS/ME but many people were eventually able to live active and productive lives despite a lingering tendency to periods of exhaustion. The same situation applies to IBS, where many people find that life changes and and IBS recedes into the background, but there is always a lingering sensitivity to food and to life.