Comorbidities

As I’ve mentioned numerous times throughout this blog, people with a form of Ehlers-Danlos Syndrome or Hypermobility Spectrum Disorders seriously win the bad health lottery when it comes to comorbidities, or conditions you have along with a primary condition. (Aka “co-occurring conditions”.) In fact, the list sometimes seems a little unreal, as it hardly seems possible a body could experience so much trouble.

Edited to add (ETA) March 1, 2022: I am finding “co-occurring conditions” to be a preferred term over time, as it’s less pathologizing and, sounds less, well, “morbid”. Alas, the title of this page is probably linked in many places so I probably won’t change it any time soon. But I just wanted to note that I’m slowly changing my terminology with time. I will probably use a mix of the two below for the foreseeable future.

But again, if I didn’t have the pleasure of experiencing several of them myself, and observe upwards of 10,000 fellow patients daily in various online support groups with every variation on the theme, I would have trouble believing it too.

But it’s true. And the sooner the medical system wraps their collective brain around this painful fact, the quicker we’ll save time, money, energy and suffering for all involved. One group now has over ~~30,00~~0 –now 60,000! – in it. They keep growing quickly!

No, we won’t have everything listed below in the same patient. But… very often one person will experience a fair number, easily ten or more of the following. And family members (if known) may experience even more as well as overlapping ones with the patient. Do keep an open mind!

Mast Cell Activation Syndrome

I think it helps when you remember that collagen runs through 80% of the body, so affects virtually every system. To borrow a phrase from MCAS savvy Dr. Afrin, a la Occam’s Razor, “do you really think there are 57 different things wrong with your patient, or maybe just a couple underlying systemic conditions that might explain it all?”

That said, one of the most common, with some of the most disabling effects yet least often diagnosed is any form of Mast Cell Disease (MCD) , which includes the more rare forms of Mastocytosis and the newly recognized much more common, but rarely diagnosed MCAS: Mast Cell Activation Syndrome. The Mast Cell Diseases Society (formerly The Mastocytosis Society until 2020) just established an ICD-10 code for this in 2016 after lots of hard work. (As well as HaTS since 2016.)

Think of MCAS as being like “extra” or “hidden” non-food and chemical “allergies” that traditional allergy testing cannot find. (The mast cells are being activated, but NOT via the traditional IgE-mediated pathway, but this can result in anaphylactoid reactions – just like allergies – just the same, though not all episodes will be fully throat-closing or require epi, so may not be recognized.)

Dr. Josh Milner at the NIH actually studied this comorbidity of atopy (allergic diseases including MCAD) and connective tissue disorders (most commonly hypermobile Ehlers-Danlos) as he shared here in the summer of 2015 at the 3rd Annual Dysautonomia International Conference. (The forms of HSD weren’t invented yet.) The study ultimately found a subset of patients who have a form of Hereditary Alpha Tryptasemia Syndrome (or Familial Tryptasemia), that is, a baseline elevated tryptase exhibiting a familial (genetic) inheritance pattern. (Described here and here in autumn, 2016.)

I’ve been given to understand that all with this condition are hypermobile, leading many to suspect it may play a role in hypermobility or hEDS. That said, this only explains a very small subset of the hEDS patient population still and this hasn’t been confirmed with any studies yet. (Correlation does not equal causation.) In other words, not all with HaTS have hEDS, and vice versa: not all with hEDS necessarily have HaTS.

Many more like myself are still very hypermobile with lots of MCAS reactions in the absence of elevated tryptase, begging the question: what else is causing our hypermobility? And others suffer oodles of soft tissue troubles and tears, and all of the pain and comorbidities of hEDS, but are not flexible at all, and never have been. And it is unclear if all have elevated tryptase or not. (I doubt it.) And I was actually in the study.

MCAD manifests in lots of GI trouble (nausea, vomiting, constipation and sudden diarrhea), frequent urination, skins signs including flushing and various rashes including hives and urticaria pigmentosa (persistent hive-like patches that wax and wane), and all signs of the various levels of anaphylaxis, which most don’t realize comes in grades according to the number of body systems involved. (Not all is throat closing!)

I’ll share more on this elsewhere, but just wanted to be sure people were aware how common we are finding it in the EDS /HMS /Fibromyalgia and autistic community. It is often mis-diagnosed as Multiple Chemical Sensitivity or porphyria. Here’s a bit on when to suspect it.

Lastly, I’ll note that there are often BOTH bio-mechanical (physical, e.g. impinged nerves, muscle tension, herniations, loose ligaments), and bio-chemical (e.g. allergy, MCAD) causes to many of our issues (e.g. headaches, frequent urination) lending to the diagnostic and treatment challenge! Don’t forget to consider both when trying to diagnose and treat. Yes, tricky! Last updated April 15, 2024:

Semi-common Comorbidities (Unofficial)

With that, here is an unofficial list of common and semi-common comorbidities (besides hypermobility) I’ve observed in the EDS community online:

Fibromyalgia
Chronic fatigue, often diagnosed as CFS/ME
Chronic Pain of ALL kinds, including RSD/CRPS, arachnoiditis, neuropathies, radiculopathy, neuralgia, fibromyalgia, etc. often invisible on scans
MCD (Mastocytosis or the newly recognized Mast Cell Activation Syndrome aka MCAS – ICD-10 code to come soon hopefully in 2014)
Fibromyscular dysplasia (deformity of the arteries, especially leading to the kidneys)
Autism (all “levels”) and related conditions (OCD, ADHD, SPD, anxiety, depression)
Auditory Processing Disorders
Semi-circular Canal Dehiscence SSCD (a rare bony defect in the petrosal temporal bone, creating a new opening between the inner ear and middle cranial fossa) causing auditory issues (hearing bodily sounds much louder than external sounds, more), can be on one side, or bilateral (both sides)
Apraxia (trouble actually moving the mouth properly to speak) and/ or situational (so-called “selective” which is a misnomer) mutism in some settings or speech burnout even in hyperverbal people who have “hit a wall” or are too stressed sometimes. Also, stuttering.
Dystonia – or movement disorders from multiple causes too (including dopa responsive dystonia)
Mood disorders, especially anxiety and depression (likely organic in origin and/or secondary from things like histadelia or high histamine from occult MCAD)
Involuntary Emotional Expression Disorder (IEED) (co-occurs with POTS) – crying easily, unexpectedly
Thyroid issues (high and low, often auto-immune despite normal TSH “levels”)
MS and other auto-immune disorders (RA, Sjogren’s, Lupus, Ankylosing Spondylitis, OA, more)
Arthritis of all kinds, especially early onset Oestoarthritis in the spine, neck and hands, but RA common also (really AI also)
Irritable Bowel Syndrome (IBS) & proclivity toward constipation, but with quick flips to diarrhea (likely food allergies/MCAD)
“No burp syndrome“, aka C-RPD in which people cannot burp at all or ever, not just sometimes
Intussusception (folding over/overlapping) of the GI tract at any age
Compression syndromes, including: Median Arcuate Ligament Syndrome (MALS), Nutcracker Syndrome (NCS), Superior Mesenteric Artery Syndrome (SMAS), and May Thurner (MT)
Incontinence at any age (often from occult tethered cord and/or MCAD or allergy induced)
Uterine or rectal prolapse, pelvic floor dysfunction
Frequent (seemingly idiopathic) nausea and vomiting (may be from impinged vagus nerve/MCAD/hiatal hernia/gastroparesis/Chiari) including cyclical vomiting syndrome
Dysautonomia of all kinds, most notably poor temperature and BP regulation (high or low, see POTS below)
Raynaud’s phenomon (blood vessel constriction from cold, stress) pronounced “ray-noe’s”) – a form of dysautonomia
POTS (Postural Orthostatic Tachycardia Syndrome) – a subset of dysautonomia involving BP drops and syncope (fainting). See also Hyperadrenergic POTS among other types too.
NMH (Neurally Mediated Hypotension) – another form of dysautonomia affecting BP
Livedo Reticularis (purplish/white “mottling” on skin surface from likely small capillary spasming)
Frequent joint dislocations and subluxations (partial dislocations) or being so-called “double-jointed“
Club foot at birth
Partial syndactyly (connected fingers or toes seen at birth)
Dupuytren’s Contracture of the hand
Snapping Hip Syndrome
Slipping rib or ribs
Mitochondrial disorders and diseases
Kidney trouble including diabetes insipidus
Diabetes miellitus and Metabolic X syndrome
Sensory Processing Disorders
Tinnitus (ringing in the ears), including Pulsatile Tinnitus from impinged vasculature near the ear
Empty Sella Syndrome (common wtih Chiari Malformation apparently too fwiw)
Insomnia (trouble falling and staying asleep, multiple causes in the EDS patient including pain and hyperadrenergia)
Sleep apnea, both obstructive airway issues and Central Nervous System (CNS) Apnea (neurologic in origin requiring a sort of breathing “pace maker”)
Cranio-cervical settling (which may cause the CNS Apnea) and attendant neuropathic issues and glaucoma
Cervical Medullary Syndrome – lends to neurologic issues from inflammation or irritation of the lower brain by the C2 bone rubbing it. Numbness, tingling, headaches, brain fog, dizziness, more.
Hypotonia (unusually weak muscles despite “training”) sometimes presenting as “floppy babies”
Syncope and pre-syncope (fainting and near fainting) and unusually low BP
Dizzyness (with or without syncope, or fully passing out)
Common Variable Immune Deficiency (CVID) of all kinds leaving us prone to frequent & worsening recurrent infections of all kinds, especially respiratory & UTI’s
Deviated septum
Chronic and recurrent sinus infections and sinusitis (treating MCAD helps some), swollen turbinates
Interstitial cystitis
Lymphedema (usually secondary and bilateral) and angioedema (the latter comes with MCAD triggering usually)
Lipedema (also spelled “lipoedema” in the UK, not the same as lymphedema, which often comes with it but is secondary ) an adipose (fat) tissue disorder causing unavoidable weight gain
Dercum’s disease (see Lipedmea above, looks a lot like that plus MCAD) causes fatty lipomas
Endometriosis
PCOS and menorraghea (very heavy periods)
NCAH (Non-classical Congenital Adrenal Hyperplasia) has also been associated with some EDS
Tendonitis and bursitis of all kinds (aka “soft tissue rheumatism”, alt. tendinitis)
Keratoconus or thinning, “droopy” or “pointy” corneas that lend to astigmatism
Uveitis (inflammation of hte uvea of the eye, common with ankylosing spondylitis)
Varicose and spider veins, often early onset, easy bruising and bleeding from same
Phlebitis
Pelvocaliectasis or pelvic caliectasis (back up and/or retention of urine in the kidneys, at any age, NB)
Migraines and headaches of ALL kinds and durations, (often driven by hydrocephalus from MCAD)
Food and drug allergies and sensitivities with a lot of paradoxic and unexpected super sensitive reactions
Bleeding disorders including Von Willebrand’s and Achenbach syndrome (deep bruises in the fingers and hands likely from spontaneous small capillary ruptures)
Strokes
Mitral valve prolapse
Aneurysms of all kinds, anywhere
Easy bruising often from no apparent cause or injury
GERD (weak hiatal sphincters and MCAD can contribute here – the stomach produces acid in response to histamine from food reactions)
Gastroparesis (slow or no stomach emptying) and dysmotility (poor digestive movement) beyond just constipation and IBS, possibly from impinged nerves & vessels (and maybe also dyssynergic defecation)
Idiopathic postprandial syndrome and/ or “Adrenergic hormonal postprandial Syndrome” (sort of “pseudo-hypglycemia” in absence of low blood sugar measures)
Chiari malformation, including occult (hidden) Chiari aka “Chiari Zero” formation (“saggy” hind brain, often protruding through the back skull, but not always)
Tethered cord
Syringomyelia or “syrinx formation” in the spinal cord (may be caused by long term hydrocephalus)
Ganglion cysts, Baker’s cysts and Tarlov cysts
Spondylolysthesis, spondylolisis (misalignment of the spinal vertebrae in various directions – front -to-back, side-to-side)
Cranial cervical instability, esp C1-C2 “owl turns” and “bobble-head” issues (trouble keeping head on neck, literally, with resulting neurologic issues)
Thoracic outlet syndrome, brachial outlet syndrome
Seizure disorders and epilepsy
Fallen arches (pes planus)
Sciatica
Bilateral hip dysplasia (both at birth, and later ability to “pop” – aka sublux – hips out and back in easily, which should be avoided!)
Pelvic Obliquity (offset hip bones, torsion in lower spine)
Cerebral Spinal Fluid (CSF) leaks including CSF (watery) rhinorrhea, CSF otorrhea (CSF leaks out nose and ears) or anywhere along the dura (lining of spinal column & brain)
Celiac disease and all forms of gluten sensitivity
Malabsorption and malnutrition and nutritional deficiencies despite diet and even supplementation sometimes. (Poor absorption). Especially low magnesium which lends to Hypokalemia.
Electrolyte imbalances (often low potassium)
Osteopoenia (low bone density) and osteoporosis (brittle bones), often early onset
Scoliosis (deformity of spinal curve) of all kinds including kyphosis (aka “roundback”, forward bent spine)
Hiatal hernia (stomach to esophagus sphincter) and all other forms of hernias just about anywhere (inguinal, duodenal, abdominal, etc.)
Costochondritis (pain at front rib attachment point to sternum)
Chondromalacia (cartilage loss) of all kinds, especially patellae (loss of cartilage in the knees, but can occur elsewhere, e.g. hips)
Frozen shoulder
Petechiae (reddish purple spots) or Purpura (essentially flat blood blisters under the skin especially in MCAD patients)
Metal and other environmental allergies, especially nickel sensitivity (ELISA testing often helpful, pre-test all implant materials)
Diastasis recti, (splitting of abdominal wall along the midline) even in males and unpregnant females
Striae aka “stretch marks” even in males and young (prepubescent) females (i.e. not always associated with pregnancy!)
Myopia (often severe), macular degeneration, astigmatism, keratoconus
Strabismus (crossed eyes) or wandering eyes from likely weak eye ligaments
Bruxism (jaw clenching, tooth grinding)
TMJ pain and issues, subluxations and dislocations (Temporo-mandibular joint syndrome, jaw alignment trouble)
Restless Leg Syndrome (RLS) and leg cramps (often eased by increased magnesium)
Neuromas in the feet
Plantar Fasciitis
Chronically low Vitamin D and B12 levels (caution urged for those with MTHFR mutations with the latter, may need a different form of Vit B)
Hyperparathyroidism (lending to high serum calcium levels and calcification in tissues)
Weak or crowded teeth, many need early or partial dentures
Receding gums
Urticaria (hives) and Urticaria Pigmentosa (persistant hive-like patches, part of MCAD above)
Aquagenic urticaria (in particular, from water exposure) and/or pompholyx (itchy water “blisters” on the hands and feet).
Hair loss early, and even in women, especially those with signs of MCAD or iron imbalances
Deviated septum (misaligned nasal cartilage)
Trouble swallowing & choking issues, often neuropathic in origin from CCI, sometimes due to floppy laryngial tissues
Esophageal spasms (can extend to anywhere along GI tract also)
Skin tears or rips, trouble suturing, would dehiscence (trouble healing post surgery, especially soft inner tissues)
Liver problems, including fatty liver and lesions, enlarged liver
Enlarged gallbladder & spleen, appendicitis (may be MCAD driven)
Vocal cord dysfunction (often mistaken for refractory asthma)
Hearing loss from a variety of causes, some bio-mechanical, others neurologic
Diverticulitis and diverticulosis
Breast Ptosis (sagging, droopy breasts)
Crohn’s and colitis
Leaky gut syndrome
Retinal detachment and tears (rips)
Dry eyes and blepharitis (bacterial eyelid infections), as well as retinal tears and more
Fistulas
Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) – hat tip Ky on Twitter for this one in November 2022. (A friend with clEDs was also just diagnosed with it a couple months ago.)
A perpetual case of dishes – seriously. From having to cook only whole, unprocessed organic foods you tolerate right? (Mine are all consuming anyway…) Last Updated April 9, 2024

Oh TWIST!

I could actually go on, but I think that’s plenty! Hopefully this is helping to broaden people’s perspective on just how incredibly wide-ranging the effects of faulty and insufficient collagen can be.

Other things that are “signs” are not listed, as they are not technically comorbidities. (E.g. stretchy skin is a sign, not a complaint, usually, as is also blue sclerae). And, I don’t want to overwhelm anyone!

I will also add that many of the above “comorbidities” are syndromes in and of themselves, and can often explain some of the other listed issues. MCAD alone can lead to many of the issues shown, as can thyroid imbalance.

Given a choice, outside of one of the very few well-trained geneticists and specialists in the world currently I’d try to work with a functional medicine doctor and/or a naturopath (functional or not) or DO (Doctor of Osteopathy) who might be willing to drill down with you to help address some of the more underlying causes of so many disorders holistically rather than trying to solve each individual issue (unless they’re show stopping or critical of course).

And, as overwhelming as this can all be, realize several things:

a) unless you’re one of the rare few with Vascular EDS or a more rare connective tissue disorder, you probably aren’t going to die any quicker than you were before you read this list (even if it feels like it, and it can feel like it sometimes alright).

And b) you need to triage and pick your battles, and address the most disabling and life-altering with your doctor first. (I would pick the top three issues for any given visit, they won’t have time for more, and maybe not even all three at that, alas. Try asking for a longer appointment whenever possible.)

And lastly c) be patient with your doctor – they can be just as overwhelmed as you are with so many issues to treat. They cannot possibly treat them all at once, nor should they. Point them here for some good resources to help them get up to speed and find answers to all their questions too.

I haven’t even treated half of mine – it’s not worth it. I’m focusing on my nutritional health and sleep, both of which have reduced my pain levels and joint instability greatly and improved several of the other issues. Work with your doctor to determine your best plan of attack, and lastly: do not worry! THAT will not help anyone.

Many issues can at least be mitigated (reduced/diminished) if not outright solved with a variety of therapies I’ll be getting to elsewhere. I keep telling my friends, my life isn’t over since my onset storm of 2012, it’s just different. (Oh but how, ow!)