Miguel Trevino, MD Internal Medicine Ehlers-Danlos Syndromes Are a Clinical Subtype of Characterized by: Connective Tissue Disorders Joint Hypermobility (joints They can be inherited and are that stretch further than varied in: normal) • How they affect the body Skin Hyper Extensibility (skin • In their genetic causes that can be stretched further than normal) Tissue Fragility, Easy Bruising Generalized Joint Hypermobility A B C

• Five or more of the • Positive family history • Pain in two or more following: • In first-degree extremities The 2017 International • Soft velvety skin relatives diagnosed • For three + month with these criteria Diagnostic Criteria for • Skin hyper extensibility • Recurrent joint hEDS have: dislocations • Striae (stretch marks ) • Atraumatic joint • Piezogenic heel papules Three Criteria (A,B,C) instability • Hernias • Atrophic scarring • Prolapse of pelvic floor ALL of which MUST be • Rectum or uterus present: • Dental crowding and high palate • Arachnodactyly (long, slender fingers) • Arm-span-to-height ratio >1.05 • Mitral valve prolapse or aortic root dilatation Evaluation of HSD There are NO Diagnostic Laboratory Tests for HSD

The Beighton Score is a Screening Technique for hypermobility

Used to Evaluate/Assess the Range Of Movement in some joints Joint Hypermobility or Laxity is the

Hallmark of most types of EDS Beighton Hypermobility Scale is widely used

The following maneuvers are performed:

Flexion of waist with Passive dorsiflexion palms on the floor of the fifth finger (and with the knees >90 degrees with fully extended) forearm flat

Passive apposition Hyper extensibility of the thumb to the of the knee >10 flexor aspect of the degrees forearm

Hyperextension of elbow >10 degrees • Assessed in the context of Age and Sex Beighton Scores Matched Norms

Scores which • ≥6 in children identify - • ≥5 in adolescents and younger adults Generalized Joint • ≥4 in adults aged 50+ years Hypermobility:

According to an • Fail to identify Males with unusually Analysis Of high levels of joint hypermobility Population Data the use of these • Over-diagnose young females as definitions may: having joint hypermobility Not a perfect tool! Clinical Subtypes: • Classical EDS (cEDS) Ehlers-Danlos • Classical-like EDS (clEDS) • Cardiac-valvular EDS (cvEDS) Syndromes • Vascular EDS (vEDS) • Hypermobile EDS (hEDS) • Arthrochalasia EDS (aEDS) 2017 • Dermatosparaxis EDS (dEDS) • Kyphoscoliotic EDS (kEDS) International • Brittle cornea syndrome (BCS) • Spondylodysplastic EDS (spEDS) Classification • Musculocontractural EDS (mcEDS) • Myopathic EDS (mEDS) • Periodontal EDS (pEDS) HSD/old JHD Hypermobile Spectrum Disorder

• Most common disorder among Hereditary Disorders of connective tissue Note: Patients with • Affects a subset of 10-20% of the general population with joint Vascular EDS may hypermobility not be hypermobile • Genetic testing unavailable Imaging Additional Echocardiogram (MRI Brain/spine) Labs (Rule out - MVP) HSD/EDS / Chiari 1

hEDS Dexa-Scan Gastrointestinal Dysautonomia (Rule out - (Caution – Complications during Evaluation colonoscopy/endoscopy such as Testing osteopenia/osteoporosis) perforations & bleeding can occur)

Pain Evaluation Bladder Dysfunction (Neuropathic/Musculo Spinal Instability skeletal)

Median Arcuate Genetic testing Ligament (Family history of Sleep Apnea Aneurysm Deaths or (Celiac Artery spontaneous bowel Ultrasound) perforation) Features suggesting an The presence of any of the following features alternative diagnosis suggests a need for further evaluation by a Medical Geneticist or EDS Specialist

• Extensive widened atrophic scars • Significant sagging skin • Premature aged appearance • Severe periodontal disease • Severe corneal thinning, retinal detachment • Significant kyphoscoliosis ( • History of organ rupture • Young-onset unexplained aortic root dilation, arterial dissection, or aneurysm • Hand and foot deformities • Unexplained significant or extensive varicosities at a young age • Recurrent large hernias • Recurrent pneumothorax • Hypertelorism (wide-set eyes), bifid uvula, or cleft palate • Intellectual disability IS NOT a specific medical diagnosis, instead, an umbrella term used to describe any Dysautonomia: malfunction of the autonomic nervous system

Dysfunction of the Autonomic Nervous System (ANS) Autonomic Dysfunction can affect you from Failure of the Sympathetic or Parasympathetic components Head to Toe. of ANS (Affecting multiple organs)

Excessive or Overactive ANS actions NOTE: Many of these symptoms can be caused by things other than autonomic Symptoms of nervous system dysfunction Ex. Medication Dysautonomia

Dry eyes/Dry Headaches/Migr Blurred vision Lightheadedness Fainting Mouth aines

Sensitivity to Difficulty Insomnia SOB/Palpitations Chest Pain light and noise Swallowing

Intolerance to Constipation/ Bladder Nausea/Bloating Abdominal Pain large meals Diarrhea Dysfunction

Heat/Cold Orthostatic Profound Abnormal Brain Fog Intolerance Intolerance Fatigue Sweating Primary Causes of Disability Patient Evaluation in patients w/ Autonomic Dysfunction in patients w/ Autonomic Dysfunction • • Orthostatic Intolerance Are there other Medical and Neurological conditions? • Fatigue • Determining the need for a referral to a Specialist • Brain Fog • Psychiatric/Psychological evaluations • Determination the extent of disability • Medication evaluation Diagnosis of Autonomic Disorders

Lab Tests

Tilt- Evaluates the patients blood pressure regulation table Test in response to orthostatic stresses  CBC  Tryptase  Beta2glycoprotein  B12  Thyroid Function  Antiphospholipid  Folate  Cortisol  Paraneoplastic Panel QSART Measures the function of the post-ganglionic  Vitamin D  Metanephrines (Autoimmune autonomic nerves that control sweat glands  Celiac panel  Urine Dysautonomia) also  Ana DS dna  Beta Prostaglandin f2 w/u for amyloid  SSA SSB (mast cell ) immunoglobulin free Cardiac Electrocardiography, Echocardiogram  Complement Total  N-methylhistamine light chain assay Workup  C3, C4  Leukotriene E4  Small Fiber Neuropathy  Iga, Igm, Igg,  Lupus Anticoagulant Skin Biopsy Postural Orthostatic Tachycardia Syndrome (POTS) - cause of POTS is unknown • A condition characterized by too little blood returning to the heart when moving from a lying down to a standing up position

Orthostatic Intolerance • Causes lightheadedness or fainting that can be eased by lying back down

• In people with POTS - these symptoms are also accompanied by a rapid increase in heart rate Common and can be disabling ……. Estimated to impact between POTS 1,000,000 - 3,000,000 in United States and millions more around the world

• Affect men and women of all ages • Most cases are diagnosed in women between the ages of 15 and 50 • Associated with the presence of excessive tachycardia and other symptoms upon standing

Orthostatic Intolerance How to do a Poor Man’s Tilt Table Test at home:

 Lay flat for 2-3 minutes. Take your bp & pulse and write it down.  Stand up for 10 minutes without moving from side to side and take BP & Pulse every 2 minutes and write down the results  Record any Symptoms while standing every minute during the test Take Note:  Lay back down for another 2 minutes, check BP & Pulse and record if your symptoms go away  If it’s too difficult to stay standing, then sit or lay back  What time of day you took the test down and stop the test  When your last meal was  What medications or supplements you were taking, if any Alpha Blockers: Terazosin Examples of… Antidepressants: Selective Serotonin Receptor reuptake inhibitors, Trazodone, Monoamine, Oxidase Drugs that can cause or Inhibitors, Tricyclic antidepressant exacerbate Anti-hypertensives: Sympathetic Blockers Anti-Parkinsonism Levodopa, Pramipexole, Ropirol symptoms of Orthostatic Drugs: Hypotension: Antipsychotics: Olanzapine, Risperidone

Beta Blockers: Propranolol

Diuretic Drugs: Hydrochlorothiazide, Furosemide ALCOHOL Muscle Relaxant Tizanidine Drugs:

Narcotic Analgesic Morphine Drugs:

Phosphodiesterase Sildenafil, Tadalafil Inhibitors:

Sedatives/Hypnotic Temazepam Drugs:

Vasodilator Drugs: Hydralazine, Nitroglycerin, Calcium Channel Blockers Symptoms of MCAS Mast Cell Activation Syndrome (MCAS)  Flushing  Diarrhea  Urticaria (Hives)  Gastric Hyperacidity  Angioedema  Abdominal Cramping Mast Cells are:  Nasal Congestion  Nausea +/- Vomiting • Part of the immune system   • Mast Cells are white blood cells found Rhinorrhea Wheezing Hypotension throughout the body  Bronchospastic Cough  Tachycardia st • 1 responder for your Immune System  Multiple Allergies  Fatigue, Lethargy  Intolerances ex. Foods,  Memory/Concentration Issues medicines, smells When Mast Cells come in contact with antigens, they decide whether  Unexplained rashes to create an Immune Response to  Allergic Hypotension protect you  Headache Diagnosis of MCAS

Tryptase Levels Before And After A Reaction

Consistent Tryptase Levels >20 may indicate other Mast cell disorder

Multiple Allergies/Or Inflammation (not IgE mediated)

Anaphylaxis with Hypotension (in response to a bee/wasp sting)

Search for Allergic Diseases like Immunocap

Citation: Up to Date Clinical Software Application: Mast Cell Symptoms and HSD/hEDS Dysautonomia MCAS some

Joint and Muscle Pain/Stiffness Dizziness/Fainting Hives Co-Morbidities of Back/Neck Dry Eyes/Dry Mouth Swelling Clicking Joints Difficulty Swallowing Nasal Congestion HSD/EDS/hEDS Joint Dislocation Shortness of Breath Nasal Discharge Early onset Arthritis Heat/Cold Intolerance Wheezing Dysautonomia Pain from Soft Tissue Injuries (Sprains) Bladder Symptoms Bronchospastic Cough Connective Tissue Weakness Neuropathic Pain Multiple Allergies MCAS Easy Fractures from Sleep Disturbances Anaphylaxis (hypotensive) Osteoporosis/Osteopenia Widespread Pain Intolerance of Foods, Meds, Smells Varicose Veins Adrenalin Rushes Rashes (Unexplained) Mitral Valve Prolapse (Palpitations) Headaches Irritability Poor Coordination Flushing (Generalized) Painful Urination Bladder Symptoms from Prolapse Nausea/Vomiting Gastric Hyperacidity/GERD Sleep Disturbances Hypotension/Hypertension Headaches Widespread Pain Fast Heart Rate Flushing (Generalized) Hiatal Hernia w/GERD Palpitations Nausea/Vomiting Bloating Sweating Hypotension (Allergic) Early Satiety Chest Pains Fast Heart Rate Abdominal Pain Cognitive Issues Palpitations Memory/Brain Fog Cognitive Issues GERD Memory/Brain Fog Diarrhea Fatigue Abdominal Pain Diarrhea Extreme Fatigue Abdominal Pain Urination Urgency/Frequency Urination Urgency/Frequency

Citation: Up to Date Clinical Software: EDS Treatment for JHS/EDS/hEDS

Avoid Exercises That Extra care for Invasive Management of Pain Physical Therapy Over Stretch Your Procedures Joints Informing Physician: • Musculoskeletal and • Muldowney or Divon • ex. Yoga, Competitive • That you may bleed more Neuropathic Protocols Dancing, Cheerleading, • Lidocaine/Novocaine May • (ex. Fibromyalgia) • 30 Minutes/Day or Every Some Martial Arts Not Work • Muscle Relaxants may help Other Day • Physical Exercise is an • That all tissues involved with spasms but can make • In A Laying Down Position important part of the should be handled gently subluxations worse Treatment of EDS because of increased risk of • Playing certain sports is ok, perforation ex. however, you must take Colonoscopy/Endoscopy extra caution to ensure your • It may take 3X longer to joints aren’t being over heal, possibly requiring stretched during the additional pain medicine exercise/sport Joint Subluxation > Ice Muscle Spasm > Heat Sleep Study (If needed) Treatment for Keep from getting Deconditioned! Dysautonomia It takes a lot of time and effort to get conditioned and Very Little Time to /Autonomic get Deconditioned! Dysfunction Exercise in lateral (flat) Compression Extra salt and water Diet position ex. Swimming, garments 30-40 mmhg Rowing, Recumbent Bike Orthostatic • Improve • Compress from knees up • Recommendation: • Organic/Whole Foods • Goal – Slowly increase Intolerance to belly button • 4 Grams of Sodium =10 • Gluten and Dairy Free for exercise to 30 • Improve Fatigue and Brain Fog • Better than just lower grams/2 teaspoons of at least 30 days minutes/day or every legs Ex. Brands: Salt • See if your intestinal other day • Heat/Cold Intolerance Mediven, Jobst, • 4 liters of fluid symptoms improve • If you’re deconditioned, • Use an umbrella to block the Sigvaris, Sankom • Electrolyte drinks: Nuun, start with 1 or 2 minutes sun • Put on first thing in the Liquid IV, Drip Drop, • Note: You may need to be morning/Take off at Scratch Labs on medications like • Limit the amount of time bedtime Midodrine before you outside • Frequent small meals vs. have enough energy to 3 meals/day exercise! • Use a wheelchair instead of • Helps with intestinal walking pooling and Gastroparesis Avoid Post-exercise Fatigue: Exercise Laying Down Stay Hydrated Go Low And Slow Treatment for Dysautonomia

• Reduce Blood Pooling by wearing compression garments and you will Reduce Adrenaline Rushes Treatment for Orthostatic Intolerance Dysautonomia • Ex. Midodrine, Northera, Mestinon, Florinef, Beta Blockers, Clonidine, Corlanor

Medications: Migraines

When taking • Ex. CGRP (Aimovig), Triptans Multiple Medications – (“Polypharmacy”) Adrenaline Rushes Use Caution • Ex. Beta blockers Propranolol, Central Alpha Agonists, Clonidine

Gastrointestinal • Ex. Zofran, Prochlorperazine, Rabeprazole, Carafate, Reglan

Bladder Dysfunction • Based on underlying causes

Insomnia • Ex. Belsomra, Ambien, Trazodone, Hydroxyzine HCL

Fatigue/Brain Fog • Mestinon, Possibly amphetamines Ex. Adderall, Provigil Important Treatment for  With Mast Cell always start with the lowest dose and increase slowly Mast Cell Activation  One drug at a time  May need to compound medications

Therapeutic Trial MCAS can be diagnosed with and may warrant H1 Blockers, H2 Blockers, If response is noted other treatments like Leukotriene Inhibitors, and Ketotifen,Xolair Cromolyn COVID 19 and Autonomic Dysfunction

COVID 19 Vaccine

In general all patients should be vaccinated • MCAS patients should pre-medicate with H1 Blockers, H2 Blockers, Leukotriene Inhibitors, and Cromolyn • Ensure you wait 30 minutes after the vaccination before leaving the facility • Have the vaccine at a medical facility in case there’s a reaction • Expect to have Flu Like symptoms and a Sore Arm for a few days • Patients who experience Anaphylaxis should consult a Mast Cell Specialist prior to getting vaccinated

COVID 19 is causing Autonomic Dysfunction (Long Haulers) Helpful Hints…. Sleep Habits

Use Natural Migraine Products Have a Set Schedule Prevention • ex. Sleep Well, Valerian Root, Lemon Balm, Passion Flower, Melatonin, THC/CBD

FeverFew • 100mg Magnesium daily Keep Head Raised Avoid Alcohol, In Your Bed Caffeine, and • About 6 -10” higher than Exercise Before Bed your body COQ 10 • 150mg daily

Optimize Bedroom Comfort Avoid Naps When Possible • ex. Lighting and temperature Sodium Supplements for Dysautonomia

Salt Stick Liquid IV Nuun Others: Vitassium

“Sport” Formula = NormaLyte, Drip 500mg Sodium, 500mg Sodium, 300mg Sodium, Drop, Skratch 370mg Potassium 100mg Potassium 150mg Potassium Labs

Use Code “Endurance” POTS30 Formula = 380mg for 30% off Sodium, 200mg Potassium Dysautonomia International FL Facebook Support Group Page

Contains helpful links, handouts, Provides support and education to videos for Patients, Employers, patients and their families while Educators, and Physicians promoting information sharing and • Annual Conference Information meetups • Note: On Home page, fill in the Search www.DysautonomiaInternational.org field with what you’re interested in researching https://www.facebook.com/g roups/DysautonomiaInternati onalFLSupport The Mast Cell Disease Society

Dedicated to patient support, scientific research, advocacy, and increasing awareness for the Ehlers-Danlos syndromes, hypermobility spectrum disorder, and related medical disorders Dedicated to supporting patients affected by Mastocytosis and Mast Cell Activation Diseases as well https://www.ehlers-danlos.com/ as their families, caregivers and physicians through research, education and advocacy

https://tmsforacure.org/ Article in ScienceDirect.com

Published in December 2018 by President and Co-founder of Dysautonomia International Lauren Stiles with 40+ Leading Dysautonomia Physicians throughout the world

Search: ScienceDirect.com Pharmacotherapy Journal: Autonomic Neuroscience Headaches & Chronic Pain 215 Volume: Cognitive & Psychological Issues Or… Managing Fatigue Sleep Disorders “Postural Orthostatic Tachycardia Syndrome” Gastrointestinal Symptoms https://www.sciencedirect.com/journal/autonomic-neuroscience/vol/215/suppl/C Autoimmunity (Please note there is a fee of $35.95 to view. Make sure you download or print within 24 hours) Mast Cell Activation Ehlers-Danlos Syndrome Adolescents Additional Articles Pregnancy in ScienceDirect.com Surgical & Dental Considerations How to Prepare for a New Patient Doctors Appointment

• Ensure you submit all of you new patient paperwork • Preform the Beighton Scale test at home prior to appointment • If you’ve never had a Tilt Table Test: Preform a Poor Man’s Tilt Table test at home if you’re not on any medications. If you’re on medications, wait for your appointment • If the visit is virtual: Ensure you have a blood pressure cuff available for the day of your appointment • Select the top 3 most disabling issues to discuss at each appointment

Make sure you’re Prepared Things to Remember • It takes time to find the right diagnosis and treatment plan • Include your family and community Goal of Therapy: • Try new things and be flexible enough to Getting patients from a 9 out change your day to day activities so that you of 10 Disability Level to a 2 can move forward and lead your best life out of 10 Disability Level with your diagnosis/disability • This is a chronic condition with ups and Note: Patients who achieve downs optimal results are the ones • When you get your period, get a virus, or who follow all intestinal flu, it’s going to knock you back recommendations every day down and you will have to fight to get yourself back up • With time and persistent effort, the crashes will be shorter and less severe and recovery will get easier