A Long Struggle for Diagnosis
Ella Engel spent her late teens and early 20s isolated in her own bedroom. She experienced chronic fatigue, pain, and dizziness or fainting when standing up. For eight years, she had no visitors and for four years, she didn’t even see her brother, who lived next door, due to her extreme sensitivity to sound, light, and touch.
In the years leading up to her isolation, Ms. Engel met nearly 40 different doctors and specialists, seeking a diagnosis or ways to ease her symptoms. “Every appointment felt like starting over, retelling the same story, answering the same questions,” she said. “I felt reduced to a case file, a cluster of symptoms, rather than a young girl watching her life progressively narrow.”
After multiple misdiagnoses, hospitalizations, and an unnecessary surgical intervention, Ms. Engel finally met GP and researcher Richard Schloeffel, who diagnosed her with a severe form of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). She is not alone in this struggle; there is no single test for ME/CFS, and people often wait six years for a diagnosis, missing out on early intervention.
Now, eight years later, Ms. Engel’s blood is helping Dr. Schloeffel and a team of Australian researchers learn more about ME/CFS. She and 60 others with the condition donated blood samples as part of a study published in Cell Reports Medicine, investigating whether ME/CFS was associated with biological changes at a cellular level.
When compared with blood samples from healthy volunteers, there appeared to be differences in immune cells and molecules involved in energy production in the blood of people with ME/CFS. “This study provides compelling evidence that ME/CFS is associated with dysfunction across multiple biological systems, challenging its dismissal as a psychological disorder,” the researchers wrote.
While the small study had limitations and more work was needed to replicate the findings, other experts said the results were a step forward in understanding if any biological processes underlie the debilitating illness. Having more information about these processes could help researchers develop tests for the condition in the future.
Understanding ME/CFS
ME/CFS is a complex condition characterized by extreme fatigue and other symptoms that make it hard to function, such as memory loss, pain, dysfunctional sleep, and dizziness. Dr. Schloeffel, who has seen about 6,000 patients with ME/CFS over his 46 years as a doctor, now works as a clinical senior lecturer at the University of Sydney. He said the condition’s hallmark feature was post-exertional malaise (PEM), where symptoms worsen following physical or mental activity.
It is unclear what causes ME/CFS, but it can be triggered by viral or bacterial infections, injury, or environmental exposures. In Australia, about 250,000 people are living with ME/CFS, with women about twice as likely to live with the condition as men. Penelope McMillan, spokesperson for advocacy group ME/CFS Australia, said the true figure could be about 500,000 if people with long COVID who meet the diagnosis criteria are included.
But Ms. McMillan, who also has ME/CFS, said unless you “almost trip over a knowledgeable clinician,” the chances of getting a diagnosis were low. “And that’s still not accounting for all the people who never get a diagnosis.” Many patients, like Ms. Engel, experience a diagnosis of exclusion, where medical professionals rule out other possibilities before considering ME/CFS.
“A system that relies on exclusion rather than identification leaves enormous room for error,” Ms. Engel said.
Finding a Way to Test for ME/CFS
To find out what was happening at a biological level in people with ME/CFS, a team led by Benjamin Heng, a research fellow at the University of Sydney, compared the cellular function of people with the condition to healthy volunteers of the same age and sex. Dr. Heng said energy production in the immune cells of people with ME/CFS was low and not “geared towards responding to pathogens.”
Researchers also observed elevated plasma proteins in people with the condition, which Dr. Schloeffel, a study co-author, said were often associated with circulation issues. “If there’s disturbance in the vascular system, disturbance in the immune system, disturbance in the cell energy function, that would explain why people [with ME/CFS] have 200 or 300 symptoms,” he said. “Because every tissue and organ in the body is impacted by this illness.”
Using machine learning, Dr. Heng’s team then generated a series of laboratory tests he said could, in future, be used to help identify patients with ME/CFS. Work is now underway to validate these tests that measure for a broad range of cellular function. If validated, the tests could be used to help diagnose people with ME/CFS easier and earlier in the future.
Study Size ‘Significant’ for an In Vitro Study
The study involved 122 people in total, a relatively small sample size. But Emma Tippett, a Burnet Institute clinical research fellow who did not contribute to the study, said the group size was “significant” for this type of research. “This figure of 61 [ME/CFS patients] is actually quite significant for an in vitro study, usually they’re closer to 10 or 20 [participants],” she said.
Dr. Tippett said in vitro studies, which involved extracting blood from a person and running complex blood tests, were “extremely expensive and extremely time-consuming.” “You are really limited in the number of specimens you can process from a resource prospective as well as a data productive point of view,” she said.
Dr. Tippett pointed out limitations in the study, such as a slightly uneven number of male participants: 23 healthy men and 14 men with ME/CFS. “While it wasn’t significantly different, it might have an impact on findings,” she said. Patients involved in the research were also at different stages in their disease process, Dr. Tippett explained, with potentially different triggers for the condition.
But, even considering these limitations, Dr. Tippett said the study was sound and helped strengthen researchers’ understanding of the complex condition. “I was very happy to see this study, which confirmed some of the previous findings for ME/CFS as well as pushes forward some of our understanding,” she said.
Ms. Engel’s Health Journey Continues
Today, Ms. Engel considers herself “one of the lucky ones” after regaining some of her mobility. With help from Dr. Schloeffel to manage her symptoms, Ms. Engel has gone from having very severe, to moderate ME/CFS. “Many people with ME don’t recover or notice any improvements,” she said.
She is grateful for the simple things in life, such as watching the sunrise, walking along the beach, showering by herself, and eating a meal at the table with her mum and dad. “While my health has improved, I’m still navigating ongoing concerns and know I have further to go,” she said. “Being part of research like this gives me hope that more effective treatments, and perhaps one day a cure, are within reach.”
