My doctor recently handed me a copy of a journal article on the relationship between Ehlers-Danlos’ Syndrome and Mast Cell Activation Syndrome. It was co-written by Dr Stéphane Daens and Dr Daniel Grossin; the President and Vice-President of GERSED (Belgium’s Francophone society for EDS research). I am actually eagerly awaiting an appointment with Doctor Daens in July 2022, so I was excited to read more about his philosophy on tackling these challenging multi-systemic illnesses.
What I read has been nothing short of life-changing. It has validated my lived experiences, confirmed the belief (held by my doctor and me) that I surely have some form of Mast Cell Disorder, and has also given me new hope that there are more treatments that I can try (and things that I can try avoiding) whilst I wait for my appointment and (hopefully) official diagnoses.
I know that many of my amazing readers are struggling with these disorders and that even more have similar undiagnosed symptoms that they “just can’t quite figure out,” so I felt that it was my duty to translate this article into English and make sure as many people as possible have access to this important information!
Disclaimer: I am not a medical professional, nor am I a certified translator. I am simply a person with knowledge of the French and English languages who believes that this information needs to be more widely circulated among patients and doctors alike.
While I am confident that I have portrayed the main points of this article in an accurate fashion, there is a high likelihood of small translation errors. If you are a native Francophone, I encourage you contact me with any errors that you find. There are a few words for which I am not confident that I found the best translation, these are followed by a “(?)” and I hope to have your input on this. This original article can be viewed at the bottom of this page.
As always, this is not medical advice, please use this information to inform your conversations with your doctor before trying any of the treatments mentioned.
P.S. Dr Daens, if you see this, I love you <3, please squeeze me in for an earlier appointment!
Ehlers-Danlos Syndrome and Mast Cell Activation Syndrome: EDMCAS?
Ehlers-Danlos Syndrome (EDS) and Mast Cell Activation Syndrome (MCAS) are known as two distinct entities, even if they are sometimes associated or have overlapping symptoms. Their diagnosis can only be established by a clinical examination (when other possible diagnoses have been ruled out). A clinical diagnosis of MCAS, by studying the signs and symptoms of the illness, leads to rapid and efficient treatment options that are easy to implement and complimentary to the usual selection of therapies offered to patients with EDS.
EDS is a hereditary connective tissue disorder which principally affects collagen (and more rarely other interstitial tissues). It does not appear to follow a pattern of Mendelian inheritance. More than one in two children with EDS have only one parent whom carries this multifaceted, multi-systemic illness. The prevalence of EDS is likely largely underestimated. EDS is widely unknown or poorly understood (and therefore undiagnosed) by the majority of general and specialist doctors.
Research papers such as Hakim and Sahota (2006), Hamonet et al. (2005), Mulvaey et al. (2013) and Morris (2016) have recently re-evaluated the prevalence of EDS to be as high as 2% of the Caucasian population. This figure corresponds to around 220 00 patients in Belgium, 1 million in France, and can be extrapolated to 17 million people around Europe and 225 million world-wide!
Claude Hammonet et al. recently confirmed a clinical somatosensory scale (which denotes certain physical sensations) for EDS at the Académie Nationale de Médecine, establishing the overall prevalence of the key signs and symptoms:
Multiple rebellious (?) pains (93%), fatigue (95%), sleep difficulties (85%), difficulty with proprioception (87%), dystonia (66 %), skin fragility (69%), neurovegetative disorders (dysregulation of the autonomic and/or endocrine systems?) (76%), easy bleeding (83%), respiratory dysfunction (79%), hypersensitive skin (69%), auditory/binocular vision disorders (80%), significant digestive issues (70%), significant oral abnormalities (70%), vesical-sphincter disturbances (59%), dyspareunia (painful sex) (61%), gynaecological problems (66%), cognitive difficulties (contrasting with a mind that is clearly developed) (68%).
The two historically recognised symptoms of EDS: stretchy skin (76%) and Hypermobility (96%), are frequent and commonly cause no functional problems. The high number of other disabling manifestations of this illness have long been obscured as co-morbidities, although they contribute largely to the diagnosis by their diverse effects.
MCAS is a disease by which the body’s mast cells (or mastocytes) degranulate too readily. The mastocytes are fragile or “touchy” (ticklish?). They may degranulate “en masse” in response to light stimulation to which they are unaccustomed or unadapted, regardless of whether the source of stimulation is known. The body’s mastocyte count is often within the normal limits, eliminating a diagnosis of Mastocytosis. The symptoms may involve any organ in the body. The type and intensity of the symptoms is very variable from person to person, and they may also vary for the same individual over time.
Dermatological: red ‘flushing” of the skin with the sensation of heat, rashes and hives.
Digestive: pain, problems with gut motility, diarrhoea, constipation, nausea, vomiting, bloating, gas, aerophagia (excessive air swallowing), excessive belching.
Cardiovascular: palpitations, ill feeling sometimes associated with low blood pressure, even an anaphylactic reaction, fainting, postural tachycardia.
Musculoskeletal: all types of joint, muscle and tendon pain, bone pain.
Urology: pollakiuria (frequent urination) (>6 per day), burning sensation when urinating, interstitial cystitis (painful bladder), libido problems.
ENT: cough, breathing difficulties, allergic type conjunctivitis and sinusitis.
Neurology/Psychology: intense fatigue, sleep difficulties, sleep apnea, vertigo, mood problems (abnormal sadness, anxiety, irritability, difficulty with concentration and memory).
The substances released during the degranulation of the mast cells are many, and explain the diversity of the symptoms.
- Platelet Activating Factor (P.A.F)
- Angiotensin Converting Enzyme (A.C.E)
- Proteolytic enzymes
- Tumor Necrosis Factor Alpha (T.N.F Alpha)
Mastocytes are involved in many bodily processes such as:
Defence against tumor proliferation
Formation of fibrous tissue
Formation of new blood vessels
Diagnosis is uniquely clinical in the absence of positive complimentary test results (a differential diagnosis?).
Specific rare case:
- When tryptase is elevated (>10ng/ml), with all the signs of MCAS and Hypermobility, we can assume a Hereditary Alpha Tryptasemia Syndrome (HATS) (?). That is to say that extra copies of the alpha tryptase exist (TPSAB1). A diagnosis by genetic testing can be difficult.
- It is equally important to rule out Mastocytosis by medullary biopsy when the basal serum rate is above 20ng/ml or in the case where the patient is fainting (or has pre-syncope symptoms), regardless of tryptase results.
In certain cases, considering the signs and symptoms, diagnoses of EDS and MCAS are difficult to make as the distinctions between the two are not always clear.
Are these disorders associated? Entangled? Mixed up? Overlapping?
Mast cells come from stem cells which form at the bone level. They circulate in the blood as progenitors (precursors to other substances) and finish maturing in the connective tissues, particularly in the skin, but also in the mucous membrane of the digestive and respiratory systems.
Are mastocytes fragile BECAUSE they finish maturing in the connective tissues that are already affected by EDS?
It’s essential, and of primary importance, that the treatments for these two syndromes can be linked and compliment each other to improve the lives of patients who have what we can call “EDMCAS” or Ehlers-Danlos’ Mast Cell Activation Syndrome.
We have to recognise EDMCAS when we see the specific signs of mass degranulation:
- Skin rashes/flushing (notably in the case of illness after a hot shower), dermatographism, itching, atopy, venom allergies
- Food intolerances, vomiting, IBD etc.
- Angioedema, anaphylactic shock
Potential triggers: (individual/personal)
- significant temperature changes, exercise, emotions, venoms
- Foods that release histamines (alcohol, eggs, chocolate, strawberry, exotic fruit, shellfish, fish, Chinese food)
- Medications (NSAIDS, opiates, anticholinergics, muscle relaxants, procaine, polymyxin, aspirin (although in certain cases it can be useful as a prostaglandin inhibitor), Amphotericin B, interferon alpha, iodine contrast.
MCAS treatments can therefore inform EDS treatments if necessary. As in the case of EDS, treatments need only be adapted if they are causing further symptoms. In the majority of cases, potential secondary effects are minimal.
H1 antihistamines – (loratadine, mizolastine, cetrizine,) (fexofenadine is an anglophone example), associated with H2 antihistamines (ranitidine, famotidine) (no longer available in Belgium 🙁 ) can be used as a first line of treatment to block the mastocytes’ histamine receptors.
Ketotifine and Montelukast – leukotriene antagonists, also have antihistamine properties and reinforce membranes (of what?).
Sodium Cromolyn (oral) – available in a vial (Intercron) but is no longer reimbursed. A mast cell stabiliser. 6-8 vials a day for adults.
We can also add simple medications like vitamin C, aspirin, cannabinoids and bioflavonoids (?). Immunosuppressants such as cyclophosphamide, cyclosporine, azathioprine, and even monoclonal antibodies like Omalizumab and Alemtuzumab are rarely useful. The use of corticosteroids is not encouraged unless there are severe respiratory or skin problems.
Before benefiting from a new therapeutic starting point, it’s important to look for the specific signs of MCAS associated with EDS.
To improve the lives of affected patients, the therapeutic and academic (the diagnostic criteria?) protocol for Ehlers-Danlos Syndrome can be enriched by the limited but precious history of cases associated with Mast Cell Activation Syndrome.
For references, please see the original article below. This copy is correct at the time of publication but you can view it in its original location here.