Are a subset of us members of a lost tribe?

Everyone keeps telling me I have Ehlers-Danlos Syndrome (EDS) even though I don’t meet the criteria. What might this mean for me and for (some) ME patients?

A little over a year and half ago, I received an email from a neurosurgeon who had watched my TED Talk. He has a subspecialty treating patients with Ehlers-Danlos Syndrome (EDS) and shared with me an observation both tantalizing and maddening: “Many of my EDS patients, after a severe infection, develop exactly your symptoms, Jen.” Tantalizing because through my advocacy for Myalgic Encephalomyelitis (ME) and the making of my film, Unrest, I met countless people with EDS, a disease that prior to getting sick I’d never even heard of. Maddening because the last thing I wanted to do at the time was open up a whole other door of potentially overwhelming possibilities.

A lot has happened to me since then. That door threw itself wide open, whether I wanted it to or not. I had my thyroid removed for cancer. That surgery led to a severe worsening of my undiagnosed craniocervical instability (CCI); I suddenly developed central apnea (I’d stop breathing for 15–45 seconds at a time, over and over and over again) and all my neurological symptoms got worse. I got diagnosed with CCI, had a craniocervical fusion to stabilize my neck, and was then diagnosed with a hematoma and tethered cord in my lumbar spine, leading to two more surgeries. All told, July to January I had five surgeries and was under anesthesia eight times. It’s been hell but it’s also taken me to places I never imagined. In the process, I’ve learned a tremendous amount about the specific, concrete mechanisms and abnormalities underlying my illness. (That’s the thinest silver lining I’ve ever put on a tough experience, but I’ll take what I can get!)

A few weeks ago, I wrote to update the neurosurgeon on my progress (he was not the surgeon who performed my recent craniocervical fusion and tethered cord release surgeries). When I described my initial response to surgery and current symptoms, as well as my new diagnoses, he told me “almost every EDS patient that I have spoken to that has gone through what you have says very similar things.”

“You almost certainly have EDS,” he said.

For the last seven years I’ve been living and fighting with a diagnosis of Myalgic Encephalomyelitis (commonly called, although hopefully that sun is setting, “Chronic Fatigue Syndrome”). That diagnosis was absolutely correct. However, in the last year, I’ve also been told so many times by EDS or EDS-adjacent doctors that I have EDS, it is now being written down regularly on my medical charts or dropped in casual conversation, even though I have never been formally diagnosed.

At first I was annoyed and tried to correct this assumption at every turn. After all, I haven’t had the genetic testing for EDS. I don’t seem to have the symptom profile of any of the 12 types for which there is a genetic test and Hypermobile EDS (hEDS) doesn’t have a gene marker. (Like ME, it is diagnosed clinically, but via criteria comprised primarily of objective signs.) Squint and I look like a lot like people with hEDS, namely because I share so many of the common comorbidities and complications associated with it: craniocervical instability, tethered cord, postural orthostatic tachychardia syndrome and mast cell activation syndrome. The only catch is that other than at my craniocervical junction, that region where skull meets spine, I’m not really hypermobile. I wasn’t hypermobile as a child. Nor am I a “stiff zebra” — a person with hEDS whose joints have stiffened up to try to cope with the instability — inasmuch as prior to surgery, I never had any kind of pain. I don’t meet any of the current, past or proposed diagnostic criteria. And by that I don’t mean that I don’t pass the bar , I don’t even check off any of the boxes. In fact, I am pretty sure I have none of the signs included in any criteria.

I share all this because there are many people in the Myalgic Encephalomyelitis and Chronic Fatigue Syndrome community who are probably in the same boat as me. We meet every diagnostic criteria for ME including the oldest criteria (like Ramsay) and the most comprehensive (like the International Consensus Criteria (ICC)). The majority of us are here in part because we got sick after an infection and post-exertional malaise/neuroimmune exhaustion is one of our most distressing symptoms. However a significant proportion of us probably also have POTS and/or MCAS, co-morbidities so frequently found in the EDS community, they are collectively called the “trifecta.” We may have weird neurological symptoms that do not squarely fit onto any list, and a growing number of us (not without some controversy!) are being diagnosed with craniocervical instability, spinal stenosis or other structural issues — co-morbidites also frequently associated with EDS.

I for one have all reasonable bonafides of an ME diagnosis when it comes to symptoms and lab testing, and was diagnosed by ME specialists. Yet after reading countless journal articles about ME, writing umpteen MEpedia medical and science pages, talking to dozens of doctors and researchers, meeting thousands of patients, and reading more stories of illness and recovery than I can count, I was surprised to find how much of my own case I had managed to miss.

And so I am left with a series of questions with no clear answers that I humbly offer up to ME and EDS researchers and clinicians to help us figure out:

  • Are the hypermobile EDS criteria incomplete? Is it possible they shouldn’t be organized around overt hypermobility in a select set of joints but rather some other standard? To be sure, people with a more classic presentation of hEDS face their own health issues and widening the criteria may dilute their meaning. How do we, then, categorize people with circumstantial evidence of a connective tissue disorder who don’t meet any current criteria (including that of hypermobility spectrum disorder) but share the same systemic symptoms and “cousin” diagnoses?
  • Or, do people like me constitute a fourteenth type of EDS? If so, how could we know or find out? Researchers at the UK biobank found a rare gene variant that encodes for a subunit of prolyl 4-hydroxylase, an enzyme involved in the production of collagen that also plays a role in the regulation of energy metabolism, and may increase the risk of developing ME. This finding is very preliminary but still turned my head. A group at Stanford is studying families to try to determine if there is a genetic link between ME and EDS.
  • Was I misdiagnosed with ME? It’s not a question I or likely anyone else can definitively answer until the science of all these diseases dramatically improves. ME, like hEDS, is a clinical diagnosis with no consensus biomarker. However, misdiagnosis seems highly improbable given that I meet every ME and CFS criteria, and my case includes many of the abnormalities found in the research literature: post-enteroviral sequelae, herpesvirus reactivation, low natural killer cell function, carnitine deficiency, pyruvate deydrogenase dysfunction, acetylcholine receptor autoimmunity a la Fluge & Mella, or my positive response to common (US) treatments for ME/CFS. Which of these findings are unique to ME? Which might we also find in adjacent diseases?
  • Or, similar to POTS, is ME a common comorbidity of some types of EDS and is EDS a common comorbidity of ME? Not all people with ME have POTS and not all people with POTS have ME, but some people with ME, Sjogren’s, EDS and several other conditions also have POTS at higher rates. How many people with ME diagnoses also have EDS? How many people with EDS also have ME?
  • Are there EDS patients who have ME but are undiagnosed (and vice versa)? Many EDS patients have what they call “fatigue” and attribute said “fatigue” to their EDS. Sometimes this is the fatigue associated with the pain of the condition itself, but is not exercise intolerance or post-exertional malaise. I’ve seen many people with EDS who use physical therapy to manage their condition do things in PT that would be very difficult for the typical ME patient. However, some descriptions I’ve seen sound exactly like post-exertional malaise. They may be using different language, but they are describing PEM. Many of these EDS patients have the multi-system symptom presentation described in the ICC (which, interestingly, references joint hypermobility as a symptom of pediatric ME) but will never be diagnosed with ME because their doctors will interpret their PEM as fatigue and attribute it to EDS. And yet there may be management strategies and emerging science that could help EDS patients who also meet ME criteria.
  • How many people with ME have one or more of the “neurological and spinal manifestations” of EDS described in this article by Fraser Henderson? This is probably the easiest and most basic question to answer. Either Jeff Wood and I are unicorns or there are a signifiant number, in which case in establishing this, we will have achieved a deeper understanding of the disease and opened up new avenues for potential diagnosis, prevention and treatment. 71% of people with fibromyalgia have some kind of spinal compression and researchers have found evidence, albeit preliminary, of cervical spinal stenosis and intracranial hypertension in some ME/CFS patients. We’ve done so little to study the spine in a disease that has “myelitis” in the name.

Personally, I think much of this is a “blind men and an elephant” problem — for clinicians, for researchers, and for many of us patients. The sooner we can understand both the overlaps and the edges, the better I believe we’ll get at diagnosing and treating all of these conditions, deepening our knowledge of their respective pathophysiologies along the way.

Near my discharge, the surgeon who operated on me shared a list of diagnoses he had arrived at in consultation with a neurologist on staff and my internist. I know getting a new diagnosis can be overwhelming, but for me it felt like closure, the most complete explanation of all of my signs and symptoms I’ve ever had:

  • Hereditable Disorder of Connective Tissue (HDCT)
  • Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
  • Mast Cell Activation Disorder (MCAD)
  • Craniocervical Instability
  • Tethered Cord
  • Adrenal Insufficiency (recent onset, common in HDCT)
  • Dysautonomia
  • Postural Orthostatic Tachycardia Syndrome
  • Intracranial Hypertension

“Hereditable Disorder of Connective Tissue” is to me the most intriguing of my new diagnoses. To be clear: we aren’t yet sure which one I have or what the genes underlying it might be. It’s the overall pattern that gives my doctors this impression. I think the tethered cord diagnosis is really the smoking gun for both the “genetic” and the “connective tissue” parts. We don’t know for certain but most people think those with adult tethered cord syndrome, like the children who have it, are born with it. I have one close family member who I strongly suspect also has tethered cord and numerous family members with hypermobility but no symptoms of any chronic illness.

Genes may have played a role, but I don’t think what I inherited was at all a determined outcome. After all, no one in my family tree has ever gotten sick like this. I think they were a risk factor and had I known what I know now, perhaps living in one of the most polluted cities on the planet for two years, Beijing, wasn’t the best idea. Or moving into a black mold-ridden apartment while I was there. Or spending as much time as I did in malaria endemic regions. Or being as adventurous as I was, eating and drinking in any restaurant and off any food stand, which may have increased my risk of contracting an enterovirus. (Just what this interplay of genetics and environment may have been in my particular case is a topic I’m keen to explore in more depth in a future post.)

There are more than 200 known heritable connective tissue disorders. It’s possible I have one that is known. As we learn more about hEDS, we might find out that is the best classification for mine. Given my luck and experience so far — everywhere I go, I seem to keep breaking the box — there is a chance my specific flavor is unknown. The question is, how many others out there might share it with me? I’d love to find out.

Read all the posts in my CCI + tethered cord series

Read this disclaimer. Crucially, surgery carries risks and it’s important to remember that in medicine, the same exact symptoms can have multiple, different causes. We have no idea how prevalent CCI is in our community and there’s been no research into its relationship with ME. We do know that it is more common among patients with EDS.