Three complex overlapping conditions Hypermobile Ehlers-Danlos Autonomic Dysfunction Mast Cell Activation Poorly understood. I am presenting observed features correlated with these conditions, though we don’t truly understand why yet. Lack of research. Three complex overlapping conditions

hypermobileEDS/HSD Hereditary Connective Tissue Disorder affecting collagen Characterised by joint laxity Autosomal Dominant inheritance (variable symptoms) No gene identified No test Criteria-based diagnosis for hEDS, remainder Hypermobility Spectrum Disorder Differential diagnosis Other rarer EDS subtypes Other rare connective tissue disorders such as Marfan’s Autoimmune rheumatological conditions Managed with physiotherapy and by symptom

Features associated with hEDS/HSD Numerous & Vague Focal or generalised joint pains or fibromyalgia, including joint dislocations, ‘Growing pains’, Complex Regional Pain Syndrome Gastrointestinal disorders like IBS, reflux, disordered gut motility Fatigue, muscle spasms, muscle weakness, restless legs, migraines Disorders of pelvic floor/bladder/menstruation Poor sleep, anxiety, symptoms of vitamin & mineral deficiencies Fragile/stretchy skin, hernias, easy bruising, poor wound healing Flat feet, varicose veins, piezogenic papules, scoliosis

Mast Cell Activation Syndrome Hypersensitive Mast Cells “Master regulators" of the immune system De-granulate releasing multiple cytokines when triggered Inflammatory & allergic symptoms Diagnosis Symptoms of MCA (Mast cell mediators elevated), biopsies? Improve with mast cell mediating medications 1-17% prevalence (NIH study – 5% Familial Tryptasaemia) Stepwise worsening with ‘stressors’

Features associated with MCAS Numerous & VaguE Gastrointestinal IBS, leaky gut, malabsorption, nausea, vomiting, disordered gut motility Swallowing problems, throat tightness, globus Cardiovascular Light-headedness, pre-syncope, syncope, labile BP Tachycardia or POTS Dermatological/Haematological Flushing, itch, urticaria Easy bruising/clotting disorders Psychological & Neurological Brain fog, short term memory dysfunction Headaches, migraines, vertigo, tics, tremors Autistic Spectrum Disorders(?) ADHD(?) Respiratory Congestion, coughing Asthma (may be poorly controlled) Vision/Eyes Ocular discomfort, allergic conjunctivitis Constitutional Fatigue, fibromyalgia-type pain, Complex Regional Pain Syndrome(?) Weight loss/gain Multiple food, drug, and chemical intolerances (especially fragrances) Autoimmune conditions Musculoskeletal Osteoporosis/osteopenia or osteosclerosis ANAPHYLAXIS Features associated with MCAS Numerous & VaguE

POTS & Autonomic Dysfunction Orthostatic Intolerance with sustained rise in pulse on standing No prevalence data – ‘frequently seen’ in specialist clinics Can be highly debilitating Diagnosis by tilt table or active stand test Triggers – pubertal growth spurt, viral illness Autonomic dysfunction can be secondary to other conditions Effective treatments are available Fluids, salt, exercise and sometimes medication POTS & Autonomic Dysfunction

Features associated with POTS Numerous & Vague Palpitations, pre-syncope Brain-fog – poor memory, poor concentration, word-finding difficulties Fatigue & exercise intolerance Tremulousness Headaches/migraines Lack of vasoconstriction Temperature dysregulation Poor sleep Anxiety

PUTTING IT ALL TOGETHER Fatigue Low BP and PoTS IBS-like symptoms, indigestion Poor healing Stretchy skin Bruising Allergies Autoimmunity Hypermobile joints, Dislocations Sprains Anxiety Poor sleep Family history Chronic pain ‘Medically unexplained symptoms’ Weak pelvic floor Migraine