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First International Francophone Symposium
"Treatments for Ehlers-Danlos Syndrome (EDS)"
Meeting Report

Medical School of Paris-East University Creteil, March 7th 2015

Professor Claude Hamonet (UPEC / Hôtel-Dieu Hospital, Paris) and Isabelle Brock, MD (Chicago). Translation by Gaël Torlay and Isabelle Brock.

 

Horse rider affected with EDS, competing with orthoses

Horse rider affected with EDS, competing with orthoses

We all have obstacles to overcome to make a difference and increase EDS awareness

 

This symposium is the first scientific meeting dedicated exclusively to the treatment of Ehlers-Danlos Syndrome. In fact, EDS is still largely ignored by the medical profession and often go unrecognized, so that the average delay between onset of symptoms and diagnosis is estimated as 20 years. This leads to difficult situations for patients and families, who often embark on a road paved with obstacles. Wandering from one diagnosis to the next, they are sometimes exposed to aggressive treatments that may adversely affect their functional and social autonomy. These may include: immunologic treatments, corticosteroid therapy with disastrous effects, mutilating and disabling surgeries (reaching the outstanding number of 45 surgeries for one patient!) When diagnosed, it is often neglected, due to a commonly held misbelief that EDS is benign. Consequences are denial of medical attention and refusal to provide health care. One medical consultant of the French Healthcare System justified his refusal of long term care coverage, with the following: "This patient obtained 100% cover for an illness not on the list, hypogonadism, requiring only substitution treatment. However, Ehlers-Danlos Syndrome does not require any treatment, and, therefore, does not fall within the scope of exemption of co-payment by social security". This symposium proved the exact opposite: Treatments for Ehlers-Danlos Syndrome do exist! They often provide significant improvement in the life of patients, considering the unpredictable evolutionary process of the syndrome and the difficulty to manage certain crises. Ignorance of the disease and its diagnosis, and therapeutic failures, often lead to inappropriate psychiatrization, expressed, "at best", by the usual phrase "it's in your mind",  and responsible, in the worst case scenario, for abusive psychiatric institutionalization.

200 healthcare professionals, mostly doctors, attended the symposium which was characterized by the quality and the originality of interventions, and the extraordinarily positive communication among participants. All attendees expressed their appreciation for an event considered a major step in the History of Ehlers-Danlos.

The presence of three professors of Rheumatology (Rodney Grahame of the University of London; Jaime Bravo of the University of Denver, Colorado and Santiago de Chile; Daniel Manicourt, UCL of Brussels) and one geneticist (Doctor Marco Castori of San Camillo-Forlanini University Hospital, Rome) with extensive clinical experience of the syndrome, shed light to a global health problem, which remains a very distressing issue in France. Participants, particularly those directly affected, were glad to realize that they were no longer fighting alone against ignorance and denial. On the previous night, experts shared a dinner meeting which contributed greatly to the constructive and pleasant atmosphere of the event. All of them expressed their desire to continue this valuable work and take part in further related projects. The creation of a medical association called GERSED, Groupe d'Études et deRecherches sur le Syndrome d'Ehlers-Danlos (EDS Study and Research Group), with its constitutive assembly held in one of the lecture hall of the Medical School of Paris-East University Creteil during the symposium, will foster future medical and scientific collaboration. Professor Grahame, Professor Bravo, Professor Manicourt and Doctor Castori, all willingly accepted to join the association as honorary presidents. Professor Boris Bienvenu, internist in Caen, will assume the presidency, Doctor Daniel Grossin, will be the treasurer, and Doctor Michel Horgues, the secretary general.

Presentations were filmed by the Audio Visual Services of the Medical School of Paris-East University Creteil. Documents will be broadly disseminated, especially through the university's website.

Professor Rodney Grahame, hosted this First International Francophone Symposium and roundtables discussions, in an excellent french, with the elegance and courtesy for which he is so well known.

Professor Jean-Luc Dubois-Randé, Dean of the Medical Faculty, welcomed all participants to this important event, shedding light to a disease wrongly considered as rare, despite its increasing prevalence. As a cardiologist, he expressed his interest in the results of today's findings.

In his introductory talk, Professor Grahame, highlighted the overlapp between joint hypermobility syndrome (JHS) and Ehlers-Danlos Syndrome (EDS), hypermobility type, who share symptoms like gastrointestinal disorders and dysautonomia. Bringing Genetics (with Brighton classification) and Rhumatology (with Beighton score) together, he paved the way for an interesting discussion, which was taken up throughout the day, and lead to the tendency to interpret EDS as a unique disorder with variable expression and various manifestations (depending on the patient and time-dependant for the same patient), and characterized by complex clinical pictures dominated by pain and fatigue.

 

 

The opening presentation was given by Doctor Marco Castori. The communication titled "From genetics to clinics-hypermobility and extra-articular manifestations and their impact on treatment: an italian contribution", was done in italian with a slideshow in english (with french sub-titles provided by Doctor Isabelle Brock and Doctor Sophie Mainguy) and simultaneous translation by Doctor Isabelle Brock and an italien teacher from the University of Paris-East Creteil. This work highlights the collaborative efforts of doctors coming from different medical specialties : genetics, pediatrics, physical and rehabilitation medecine, dermatology, pneumology, ophthalmology and statistics. Doctor Castori insists on the notion of pleiotropy (a single gene influences multiple phenotypic traits) and recalls that hypermobility naturally decreases with age: the Beighton score tends to fall below 5 at the mean age of 33 years (which is the recommended cut-off value for diagnosis). He differentiates localized and peripheral hypermobility from generalized joint hypermobility. Common associated symptoms are: fatigue, dystonia, gastrointestinal disorders, headaches, tachycardia. The differential diagnosis includes Marfan syndrome and Loeys-Dietz syndrome. Doctor Castori considers that Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome, constitute a homogeneous group sharing the same clinical and molecular features. The hypothesis of a non-mendelian transmission is discussed. In this light, JHS and EDS-hypermobility type appear as a congenital disorder that evolves over time. The natural history of the disease can be reconstructed and lead to appropriate preventive measures. Sleep studies, MRI brain scans and pain management plan are part of the follow up proposed to his patients. A severity score is urgently needed to better follow disease evolution and tailor treatments to the specific needs of individual patients. His  recommendations include: healthy lifestyle with regular physical activity, vitamin supplementation (C and D), magnesium, melatonine, and L-Carnitine. Local treatments should be preferred to centrally acting medications. Morphine is highly contra-indicated.

 

 

Doctor Richard Amoretti presented the cardiologist's clinical approach to Ehlers-Danlos Syndrome, insisting on pseudo-cardiac symptoms which are in fact extra-cardiac manifestations. Common signs are: tachycardia crises accompanied by palpitations, precordial chest pain, shortness of breath related to other respiratory symptoms of EDS. A complete exploration of arterial vessels is recommended for all types of EDS, to look for any arterial fragility or dilations. Heart conditions (regurgitations, prolapses) are common and relatively harmless. The heart appears to be the strongest organ in the body of EDS patients. Low dose Beta-blockers significantly  improves tachycardia, related to dysautonomia. Hypotension and vasomotor instability are of particular concern.

 

 

The following session was devoted to the presentation of 15 posters, related to the topics covered by oral communications: EDS joint mobility with evidence of muscle retractions (harmstrings), EDS respiratory manifestations, postural data, dysautonomia, walking orthoses, effects of thermal treatments, and psychopathological manifestations of EDS. Two practical workshops were organised: one on orthoses, and the second, on oxygen therapy and use of Bird Percussionator®, with the latest design in demonstration.

The first round table was dedicated to proprioception and locomotor disabilities. First to deliver his oral presentation, Professor Roland Jaussaud from Reims, discussed the importance of proprioceptive disorders in EDS patients, that may be evaluated following techniques used in posturology, and is confirmed by the postural improvements gained with orthopaedic insoles, throracolumbosacral orthesis, and compression garments.

Professor Claude Hamonet and Mrs. Elodie Vlamynck (orthotist), presented the principles, technology and performance of orthotics. The original and innovative intention was to compress soft tissues to improve the perception of sensors inserted in over-flexible connective tissue (Créteil, 2000). The first orthotics were developped by the Thuasne Pharmaceutical Company research team (Saint-Etienne, France), from garments designed for the treatment of severely burned patients. The following study demonstrated without doubt the effectiveness of these new medical devices. Benefits included: improved efficiency of sensors located in a poorly reactive connective tissue (by compression), increased proprioceptive stimulations (when combined with orthopaedic insoles, lumbar belts and hand orthoses), and reduced contact pain via Gate control. Technology has improved dramatically over the last few years, in terms of texture and adaptation, so that compression garments have now become an integral part of EDS treatment plan, particularly for children. Early application, associated with proprioceptive rehabilitation and movement neurological regulation, represent a reasonable objective. Therapeutic effects of compression garments were assessed by Mrs. Elodie Vlamynck when completing the final project for her university degree (Paris-East University Creteil, 2010). Common findings were: improved functional abilities (particularly walking) and significant pain relief associated with reduced intake of painkillers (including morphine-type medications, for those concerned). 1300 patients benefited from these orthoses. Mrs. Hutin, engineer, conducted a study on gait analysis (under publication) in the Department of neuromotor rehabilitation of Professor Jean-Michel Gracies (Henri Mondor Hospital, Paris). It confirms the improvement in gait parameters (e.g. step length, rolling motion, gait speed), in combination with or without orthopaedic insoles (median retrocapital or/and arch support), which also play an important role in proprioceptive input. To date, nearly 2000 sets of custom-made garments have been prescribed and used. Great progress has been made in the tolerance of these orthotics, particularly in warm weather conditions, and to reduce skin reactions in areas prone to friction or compression. Current research into new materials, carried out in co-operation with a team of engineers, promises to generate further improvements. Compression garments come in addition to pressure relieving supports (cushion, back support and mattress with memory effect) which are systematically prescribed to our patients. The lumbar belt, preferably with 3-points pressure system (lumbar and bilateral anterior scapular support) is one of several assistive devices that we recommend to improve proprioception. Resting hand orthosis, are made from a semi-rigid and light material (Scotchcast), not only because those made out of thermoplastic are often badly tolerated (due to their weight and rigidity) but also to avoid skin injuries in patients with increased skin fragility. These orthoses are indicated to prevent wrist pain, typically caused by writing or similar uses, and provide almost instant relief. Functional hand orthosis, designed in the same material, or eventually ready-to-wear (removing stabilisation bars to lower the weight) facilitate functional use of the hand, in the presence of pain.

 

 

For the past few years, the team of Hotel-Dieu has been prescribing rigid orthesis - designed by Monsieur Rami Haidar (ortho-prosthetist) and his colleagues in Lille - to stabilize the pelvis and torso (custom molded seats adjustable in height with tables, similar to those used by children suffering from early brain injury, rigid trunk orthoses and cervical collars). Initial results are very promising, particularly for school children. Resting orthoses, initially intended for children to ease pain during bedtime, are increasingly requested by adults who tend to feel less pain, and uncomfortable sensations in the legs, when waking up. Major walking devices (initially, Chignon orthoses with dynamic assistance, now replaced by articulated orthoses with free-motion joints and sometimes, safety stops) have been prescribed to over 100 patients affected by EDS. A recent study conducted by the team of Mr. Rami Haidar on 22 patients, showed positive and encouraging results : improved functional ability and significant pain relief.

 

 

Docteur Geoffroy Nourissat (orthopedic surgeon, Maussins-Nollet Clinic, Paris), Professor Levon Doursounian (Chief of orthopedic surgery at Saint-Antoine Hospital, INSERM UMRS-938, Paris) and Professor Claude Hamonet presented the results of their shared experience, gained in the first 3 years of a new combined medical/surgical consultation for EDS patients, set up in Hôtel-Dieu Hospital. The main objectives are to discuss indications for surgical treatment, to provide the best orthopedic care for every patient, and to assess the overall importance of surgery in Ehlers-Danlos Syndrome. In the absence of genetic testing for EDS, hypermobile type (the most frequent type of EDS), diagnosis is based entirely on clinical signs, among which articular problems are frequent. The most common orthopedic manifestations are: pain, dislocations, hemorrhages and hematomas of the limbs. The shoulder is the most mobile joint in the body, thus it is frequently affected, and suffers misdiagnosis often leading to surgical failure. Clinical manifestations are: dislocations, scapular dyskinesis (impaired shoulder proprioception, altered scapular position to prevent pain, dance of the shoulder blades, periscapular pain). Not necesseraly linked to capsular and ligamentous laxity, symptoms are more likely to arise before the age of 35. Medical imaging does not show any osteoarticular injuries in particular. Treatment strategies aim to improve proprioception (mainly using compression garments), relieve periarticular pain and prevent dislocations due to dystonia (when present) with antiparkinsonian medications. Hyperlaxity associated to EDS is responsible for luxations and may affect the outcome of surgery. Dislocations can occur at any age. They are atraumatic and indolent at the time of injury. If early surgery is often the best course of treatment for most patients, it should be delayed for EDS patients, and only be considered as a last resort to restore comfort (when all else failed). The risk of osteoarthritis is highly unlikely, as with any other joint. Surgery should follow specific guidelines: only anatomical lesions should be treated, cartilage should not be touched, reduce glenohumeral mobility (if shoulder mobility is the issue). Surgery should always be undertaken with caution (plications). Painful shoulders are characterized by weak spatial stabilizers, with impaired proprioception, and possibly, a protection against rotator cuff injuries. Rehabilitation is mainly based on self-reeducation, with little immobilization (removable arm sling), to prevent aggravation of proprioception disorders. Surgeons should be aware of several particularities: abundant bleeding, slow healing process requiring gradual sutures removal to avoid scar disunion, bone graft resorption (possibly due to vascular problems?), prolonged consolidation of bones and ligaments. Effects of general anaesthesia are often minimized, with the risk of early awakening. Local and epidural anaesthesia are not very efficient. All in all, in terms of surgery, EDS patients suffer common pathologies with atypical presentations. Conventional therapies often have adverse effects. A sound knowledge of the syndrome and its particularities, is essential to tailor surgical treatment to the specific needs of EDS patients.

Dr Daniel Deparcy (Chief of the Physical Medecine and Rehabilitation Départment, Tourcoing Hospital centre), made a very detailed pathophysiological analysis of muscular and postural disorders in EDS and presented the benefits of rehabilitation techniques based on Kabat mérhodv  to regain muscular synergies. This presentation completed perfectly previous analysis of Pr Jaussaud and Pr Hamonet on proprioception and proprioceptive effects of orthoses. It gave participants the opportunity to better understand and follow the postural and movement anarchy that is commonly observed in EDS. Dr Deparcy provided specific rehabilitation principles for patients affected with EDS. He described the kinetic chain. It starts with the foot conformation, gets dampened in the crural region, and is channelled towards the lumbar rachis via the pelvis. It ensures proper alignment of curvatures to offer the right balance with the descending chain. He considers the diaphragm as a breathing motor, generator of lordosis, modulator of inspiration, and aspirator of fluids. He establishes a link between rachis and gestures, following Kabat and Sohier techniques, and Zen postures.

 

 

Dominique Ouhab (physical therapist, Paris), reminded participants of physiotherapy principles and provided useful guidelines for effective patient management. As a proprioceptive re-education, physical therapy can benefit greatly from the use of compression garments during sessions. Oxygen therapy before sessions also seems logical. Basic recommendations should be followed: avoid exercises that may lead to immediate or delayed onset of pain; prioritize isometric exercises while in a stationary position (with no movement); prefer gentle pacing of exercise without sustained contractions and limit the number of repetitions; provide rest intervals; sessions should be adapted to patients functional state, particularly the neurovegetative (dysautonomia), to prevent hypotension and fatigue; use all physical appropriation methods available (relaxation and derivated techniques). Massages combine great analgesic effect and muscle-relaxant properties, thus improving proprioception. Pressotherapy is effective for the treatment of lymphoedema associated with EDS. Muscle retractions are common (triceps and harmstrings). Respiratory re-education is needed to show how to use the diaphragm and abdominal muscles more efficiently. Learning voluntary control of respiration (brief respiratory pause in case of inspiratory blockage, small voluntary expiration, pause, short inspiration, etc.) is also of importance. These techniques should be used during sessions and repeated frequently as self-rehabilitation. Singing is a great way to improve bucco-laryngo-tracheo-diaphragmatic control and helps prevent aphonia and swallowing problems, frequent in the syndrome. Individual cryotherapy, was mentioned by a physiotherapist from Rennes, who has started using it in his practice. Performed at very low temperature, it was dedicated until recently to athletes. Although the number of EDS patients treated with this new therapy remains scarce, it may represent a promising and innovative therapeutic approach.

 

 

Doctor Michaël Delarue, (Hendaye, Toulouse), odontologist, presented his vast knowledge and experience of dental and oral care in Ehlers-Danlos Syndrome, which was also the subject of his doctoral thesis on odontology. He highlighted the lack of awareness about EDS, by patients and fellow practitioners, and insisted on the need for more epidemiological data (still relatively scarce and unproductive). He describes anatomic anomalies (high cuspids, deep grooves, abnormalities in root morphology, microdontia), structural anomalies (intrapulpal calcifications, enamel hypoplasia), occlusal problems (misaligned teeth, tendency to prognathism), articular disorders (recurrent dislocations, chronic facial pain). He also outlines the fragile and thin mucosa, the absence of the inferior labial and/or lingual frenula (Gorlin's sign), and periodontal diseases (early periodontitis, periodontal complications are present in 34% patients). Conservative dentistry treatments are to be started as early as possible, same with anticaries prophylaxis, atraumatic prosthodontics, preventive periodontal care and regular check ups. Surgery should be performed with extreme precaution to prevent the risk of abnormal bleeding. Healing is often slow and difficult. Local anesthetics may not be efficient. He recommends the following: dental procedures performed more rapidly, recare appointments every three months and the use of orthodontic contention after treatment. Doctor Delarue concludes that early detection of these patients, based on a thourough interrogation and complete medical examination, is key to improving treatment. He insists on the importance of following appropriate precautions and deplores the absence of a specific standard of care.

 

 

Relying on his extensive clinical experience (nearly 3000 patients treated), Professor Jaime Bravo (Denver, Colorado and Santiago de Chile) presented dysautonomia in Ehlers-Danlos Syndrome, hypermobile type (Dysautonomia in EDS-III), and shared his innovative treatment plan. The communication was done in English with a slideshow in english (with french sub-titles) and simultaneous translation by Carolina Baeza-Velasco. For Professor Bravo, dysautonomia plays a major role in symptoms reported by patients. An impaired autonomic nervous system is responsible for extreme fatigability present throughout the day, regardless of the effort exerted. These symptoms are commonly mistaken for depression, fibromyalgia, chronic fatigue syndrome, hypothyroidism, etc. Patients are often considered as lazy by their circle of family and friends, because fatigue can prevent their involvement in social interactions. Undiagnosed dysautonomia significantly impairs EDS patients' quality of life. Many problems are linked to soft tissue fragility: pelvic organ prolapse, joint disorders, mitral valve prolapse… Professor Bravo prefers the term EDS-type III rather than hypermobility type, since in a series of 1751 patients, 55% scored 3/9 or less on the Beighton score. The following symptoms of dysautonomia are present: chronic fatigue with persistent sleepiness, low blood pressure, cold intolerance, memory problems, impaired concentration, attention and orientation. To the best of his understanding, dysautonomia in EDS is due to a weakness of the vein walls of the lower limbs and abdomen,  linked to an altered collagen. It is responsible for venous stasis and deprives the brain of sufficient blood supply, cause of ischemia. Orthostatic hypotension is common in patients with EDS (Postural Orthostatic Tachycardia Syndrome/POTS). However, if arterial pressure is normal, dysautonomia will remain undiagnosed, thus untreated. Aggravating factors are: dehydration, high altitude, prolonged standing, rapid changes in position, staying in one position for a long period of time, walking slowly and heavy meals including alcohol. His study followed 1734 patients. Dysautonomia is present in 56,1% men and 79,5% women under the age of 30. Osteoporosis affects 13,6% men and 14,9% women in the same age group. Pr Bravo recommends the following treatments: avoid sitting or standing without moving for prolonged periods of time, avoid walking at a slow pace; lie down as soon as first symptoms appear after a heavy or fairly alcoholic meal; keep drinking until urine is clear; wear elastic compression garments (particularly on the lower extremities); a high sodium diet (in the absence of any specific contraindication), moderate aerobic exercises. Fludrocortisone, Midodrine, Atenolol are effective in preventing tachycardia. Anti-depressants are prescribed. As a conclusion, Pr Bravo shared a few pictures of artists (dancers, musicians), and athletes, who were able to turn their hypermobility into an asset.

 

 

Second round table session (on fatigue, sleep disturbances, respiratory manifestations, dysautonomia and dystonia) and third one (on pain, psychopathology and social inclusion) were combined to minimize the delay due to an overly ambitious programme for a first symposium. Some interventions could not be presented and will be the subject of an additional post-conference dissemination, but will be included in a joint publication by Elsevier.

Professor Claude Hamonet (Paris-East University Creteil and EDS consultation, Hôtel-Dieu Hospital, Paris), Franck Leroux (ASV Company, Paris), and Monique Vienne (IMAP Company, Nice), discussed the prevalence of respiratory manifestations in EDS patients and the beneficial effects of oxygen therapy and percussionator®. A statistical analysis based on data collected from the first 644 patients receiving this treatment between 1999 and 2010, was performed by the team of Pr Philippe Ravaud (Center of Clinical Epidemiology & Medical Statistics, Hôtel-Dieu Hospital, Paris). Dyspnea, particularly when climbing stairs, occurs in 85% patients. Inspiratory blockages are present in 65% subjects. Dysphonia is found in 45% women. 35% have recurrent bronchitis, women are more severely affected than men. Aspiration of food or fluid into the airways occurs in 45% women and 25% men. The initial study was repeated in 2013 with 107 EDS patients with the following results. Dysphonia is present in 52% individuals. 93% suffered frequent upper respiratory tract infections, often complicated by otitis, mainly during childhood. Aspirations are present in 33% subjects. Chest pain is felt by 81% patients. High prevalence of gastroesophageal reflux (86% subjects). Exceptionally: pneumothorax, accute respiratory failure requiring resuscitation. Pulmonary function tests are normal. 20 patients perfomed the 6-Minute Walk Test (6MWT); results are waiting to be interpreted. Several factors seem interlinked: absence or distortion of signals transmitted towards respiratory centers, by sensors drowned in poorly reactive connective tissue, resulting in sensation of respiratory distress; diaphragmatic function impaired by overly flexible abdominal wall and abdominal bloating; chest pain responsible for thoracic restriction; painful and impaired respiratory muscles (diaphragm more specifically). The link with fatigue seems to be of great importance. Simple things can make a real difference, like, taking voluntary control of breathing using the following exercise: respiratory pause, small expiration, small inspiration, small expiration, larger inspiration... Orthoses (vests, belts) improve abdominal motion and diaphragmatic function as well as costal proprioception. Lidocaine injections into trigger points, to relieve costal and xiphoid pain, are most effective.

Carl Leroux's team conducted an experimental study on 30 patients. Data collected before the introduction of home oxygen therapy, and after 30 days of treatment, were compared and lead to the following results : 47% of participants used oxygen therapy twice a week; 57% for a duration of 20 minutes; 64% with a volume of 1,5L to 2,5L per minute. Fatigue is improved for 73% of patients, 93% if those feeling episodic relief are included. 67% of participants experienced efficacy on headaches. 53% reported an improvement of subjective quality of life.

 

 

Monique Vienne (IMAP Company; respiratory therapist, former student of Dr Bird, Bird Institute, USA) introduced Bird Percussionator® in France. This medical device has been used successfully by patients with EDS to reduce  respiratory manifestations (blockages, dysphagia, dysphonia) possibly due to an impaired broncho-thoraco-diaphragmatic proprioception. In 2011, Monique Vienne conducted a study of 40 patients, as a final project for the degree "Disability, fragility and rehabilitation" (Paris-East University Creteil). Besides confirming the effectiveness of Bird Percussionnator, the study also showed a significant effect on fatigue. Believing that hyperventilation provoked by the percussionator was responsible, oxygen therapy followed as a trial. Results were immediate and oxygen therapy, with or without percussionator, has now become an integral part of many effective treatments for EDS. However, the road ahead remains long. Monique Vienne presented several publications (A.W. Morgan and Coll., M.J. Cavanaugh and D.M. Cooper, R. Dinwiddie and S. Sonnappa...) to reaffirm the importance of respiratory manifestations in Ehlers-Danlos Syndrome, which are too often neglected.

 

 

Doctor Arnaud Metlaine (National centre for rare hypersomnias, Professor Damien Léger, Hôtel-Dieu Hospital, Paris) presented a paper titled "Sleep, fatigue and vigilance in Ehlers- Danlos Syndrome". Dr Métlaine followed 98 patients diagnosed with Ehlers-Danlos Syndrome, hypermobility type, in Hôtel-Dieu Hospital. All patients reported complaints of fatigue and sleep disturbance. Participants (19 men and 79 women, aged between 15 to 75 years old) underwent complete exploration of vigilance and sleep. Clinical observations lead to the following results: nocturnal leg cramps, sleep latencies, sleep-disordered-breathing (SDB), high prevalence of sleep complaints and impaired vigilance, total sleep time. Less than 60% of patients obtained less than 7 hours of sleep per night. 24% got less than 6 hours. There is no association with anxiety or depression. Sleep fragmentation is observed. Vigilance is correlated with fatigue. An international publication of this paper is in preparation.

 

 

Carolina Baeza-Velasco and Antonio Bulbena (Department of  of Psychology of Paris-Descartes University, Department of Psychiatry at Autonomous University of Barcelona) presented an outstanding report titled "Joint Hypermobility Syndrome, SED and Psychopathology". This is a major breakthrough for patients with EDS who are often thought to have psychopathological troubles, without consideration of manifestations specific to the syndrome. Madame Carolina Baeza-Velasco completed her doctoral thesis in psychology focusing on this subject. Marching in rhumatologists footsteps, she follows the common thread running from joint hypermobility to Ehlers-Danlos Syndrome. Psychiatric conditions associated with the syndrome in the medical litterature are: depression, autism, attention deficit and hyperactivity disorder, substance abuse, eating disorders, personality disorders, anxiety disorders. Patients with joint hypermobility are twenty-two times more likely to suffer from anxiety than other rheumatological patients. The following hypotheses have been proposed: difficulties in dealing with disabling syndrome, genetic factors, structural brain abnormalities specific to EDS. Several factors may lead to anxiety: an autonomic nervous system dysfunction known as postural orthostatic tachycardia syndrome (PoTS), enhanced psychophysiological reactivity (interoception) and tendancy to amplify somatic sensations interpreting them as intense, noxious and disturbing (somatosensory amplification).  This is commonly observed among patients with EDS, who can often describle accurately the path that the blood follows through their vessels. Anxiety is an additional cause of impairment. It is responsible for poor quality of life, has a negative impact on observance and increases pain perception. The need to explore psychiatric symptoms in patients with joint hypermobility and EDS is enormous. A very limited number of studies have explored the impact of psychosocial interventions for EDS patients. However, two studies based on Cognitive-Behavioural-Therapy (CBT) for the treatment of pain and emotions in EDS patients have shown encouraging results.

 

 

Mr Philipe Bézire, psychologist (Paris) completed his research for the degree "Disability, fragility and rehabilitation" (Paris-East University Creteil-2010) focusing on the management of patients with Ehlers-Danlos Syndrome. He delivered a presentation titled "A light at the end of the tunnel, trial of integrative therapy", relying on 7 years of clinical experience following patients and families affected with EDS. Mr Bézire considers his work more of a psychological support than an actual therapy. He takes patients through the following steps: situational analysis, perception of the disease, acceptance of the syndrome, life balance of those affected, and finally, ways to live a more integrated life.

 

 

Dr Jennifer Flandrin discussed gynecological aspects of the disease, on behalf of Professor Gompel, gynecologist and endocrinologist, who was unable to attend the symposium. She presented the results of a study awaiting publication, conducted on 387 women diagnosed  with Ehlers-Danlos Syndrome, hypermobile type (in French with a slideshow in English). Common findings were: heavy menstrual bleeding and metrorrhagia (in women already affected by increased bleeding tendancy), frequent dyspareunia, dysmenorrhea, spontaneous abortion, and  possible confusion with endometriosis. The many hormonal changes that occur during a woman's lifetime (puberty, pregnancies)clearly influence symptoms. Hormonal treatments are proposed.

 

 

Doctor Rabih Klink, pediatrician and pneumologist, made a significant contribution to the diagnosis and treatment of children with Ehlers-Danlos Syndrome in a department of Northern France (l'Aisne), more specifically in the town of Laon. He improved doctors awareness of the disease, including school doctors, and organised the screening and management of 300 affected families. Today, he gave a clinical description of his patients, which not surprisingly echoed clinical pictures presented by other symposium participants, proving once more the clinical uniqueness of Ehlers-Danlos Syndrome.

Professor Claude Hamonet presented the diverse manifestations of the disease, relying on years of clinical observations at Hotel-Dieu Hospital. A considerable convergence with the descriptions of previous speakers, particularly those of Dr Castori, Pr Bravo and Pr Grahame,  is evident. EDS symptoms often contribute to impaired quality of life and functional impairment. Therefore, care strategies that prioritize symptomatic relief are needed. The most common symptoms are: diffuse pain, fatigue, proprioceptive and articular disorders, sleep disturbance, dysautonomia (including vascular disorders of the extremities, hypotension, chill, dry mucous membranes, temperature regulation problems), bleeding, hypermobility coexisting with muscle retractions (triceps and hamstrings), fragility of the skin, dystonia, respiratory difficulties, oral and dental problems, gastroesophageal reflux, visual fatigue, hyperacusis, memory and attention problems.

Appropriate treatment strategies will aim to relieve and even eliminate these symptoms.

Professor Daniel Manicourt (UCL, Brussels) endorsed the need for better care for EDS patients who are just as ignored in Brussels, as they feel in Paris or anywhere else in the world. Participants expressed appreciation for his tremendous dedication to patients with Ehlers-Danlos Syndrome and welcomed his humanism. A particular aspect of Belgian Social Security Office is the mandatory use of dermal histology and electron microscopy-a negative result does not necessarily exclude the diagnosis. Pr Manicourt highlighted the need for multicenter international studies. Hopefully, this symposium will pave the ground for this highly desired international cooperation.

 

 Pr. Rodney Grahame

Professor Grahame ended the symposium with a complete and historical review of the symptomatology, presented in an excellent french. He explained how the symptom pyramid changed over the years, and how its base had to be broadened with the influx of new symptoms.

As a Professor of Clinical Rheumatology with extensive experience, he made a severe but realistic assessment of the situation, picturing the dark side of the disease management and welcoming small but encouraging signs of recent progress.

The dark side is the lack of an identified genetic marker associated with the disease. Genetic technology will only play a role in patients lives when available. Unfortunately, patients affected with Ehlers-Danlos Syndrome are not well-cared for by medical professionals, and often feel that they are not listened to, nor believed. They are neither diagnosed, nor treated. Professor Grahame believes that we are confronted with a major international public health issue. To his knowledge, no other disease has been so seriously neglected, patients knowing the syndrome better than any doctor.

The bright side is the growing number of professionals actively dedicated to the syndrome, the existence of effective treatment, the creation of national reference centers, the opening of specialized treatment centers, the existence of active associations and support groups.

 

 

The symposium ended with this message of hope. All attendees uninamously agreed on the progress made to improve the lives of families affected by this seriously neglected genetic disease, often the source of disability. All four invited participants shared their appreciation of the event and expressed their willingness to establish a new promising collaboration, followed by future scientific meetings. All reaffirmed the need to take urgent action to improve awareness and education, to endorse patient advocacy, and to offer effective management strategies. It is imperative to develop multicenters studies to expand clinical and treatment research and to investigate the relationship between phenotype and genotype in Ehlers-Danlos syndromes. A joint declaration by speakers from England, Chili, Italy, Belgium and France is in preparation.

Thus, this First International Symposium on Ehlers-Danlos therapeutics is a natural continuation from the First International EDS Conference held in Ghent (Belgium) in September 2012, and appears as an introduction to the EDS International Symposium organised in New York City during May 2016, by EDS UK and the Ehlers-Danlos National Foundation (USA).

The symposium will be held every year in order to discuss recent findings, improve knowledge-sharing and promote new therapeutic advances in the field.

The next symposium will be held on March 19, 2016

It will bring together health professionals, psychologists, social workers, and students in these fields.

Pre-registrations and paper proposals or posters, can be submitted as of now to the GERSED medical association (EDS study and research group), via the following links: michel.horgue@free.fr or pr.hamonet@wanadoo.fr

A post-conference workshop intended for patients and families, will be held on June 11, 2016. If appropriate, they may choose to invite their doctors, health professionals, and education teams.