Triad Basics

	MCAS (Mast Cell Activation Syndrome)	POTS (Postural Orthostatic Tachycardia Syndrome)	hEDS/HSD (Hypermobile Ehlers-Danlos Syndrome)
Common Symptoms	Common Symptoms Flushing Hives, rashes, or itching Nausea/vomiting Abdominal pain/diarrhea Anaphylaxis Tachycardia Fatigue Hypotension Brain fog Bone pain Headaches Food/medication intolerances Wheezing/shortness of breath Swelling (angioedema) Anxiety or Panic attacks	Common Symptoms Dizziness/lightheadedness on standing Tachycardia Palpitations Fatigue Brain fog Nausea Heat intolerance Sweating abnormalities Exercise intolerance Headaches/migraines Chest pain Gastrointestinal discomfort Anxiety-like symptoms	Common Symptoms Joint hypermobility Chronic joint pain Frequent dislocations/subluxations Soft/stretchy skin Poor wound healing Fatigue Gastrointestinal symptoms (e.g., IBS) Easy bruising Chronic pain Dysautonomia symptoms Pelvic floor dysfunction Sleep disturbances We recommend this symptom guide from Dr. Linda Bluestein
Typical Patient Demographic	Typical Patient Demographic Affects all genders but more common in females Often starts in childhood or young adulthood Can occur in individuals with allergies or autoimmune conditions	Typical Patient Demographic Primarily affects females (80–85% of cases) Common onset in adolescence or early adulthood	Typical Patient Demographic More common in females Often apparent in childhood or adolescence but may worsen with age Family history of hypermobility syndromes common
Diagnostic Criteria	Diagnostic Criteria Consensus-2 Criteria: Symptoms in ≥2 organ systems (e.g., skin, GI, respiratory) Elevated mast cell markers (e.g., histamine, prostaglandin D2) Improvement with mast cell-targeted treatment Sources: Afrin et al., 2020 (Link) "Consensus-1 Criteria" in Valent et al., 2012	Diagnostic Criteria Heart rate increase ≥30 bpm (≥40 bpm in adolescents) within 10 minutes of standing, without a significant drop in blood pressure Symptoms ≥3-6 months Exclusion of other causes (dehydration, anemia, etc.) Sources: Raj, 2013; PMD guidelines, 2021	Diagnostic Criteria Beighton score ≥5 (adults) with systemic signs (chronic pain, skin abnormalities) Exclusion of other connective tissue disorders Musculoskeletal complications (joint instability) Sources: Malfait et al., 2017
Underlying Mechanisms	Underlying Mechanisms Mast cell dysregulation → excessive mediator release (histamine, prostaglandins) Triggers vary: allergens, stress, temp changes, infections Multisystemic symptoms affect skin, GI, respiratory, cardiovascular, neuro	Underlying Mechanisms Dysautonomia → impaired blood vessel constriction & excessive HR on standing Inadequate blood flow to the brain & overactive sympathetic system Often linked to low blood volume & vascular tone	Underlying Mechanisms Collagen/connective tissue abnormalities → joint instability, skin issues, vascular problems Weak connective tissue affects many systems (GI, cardiovascular, neuro) Often linked to dysautonomia & chronic pain
Non-Pharmacological Management	Non-Pharmacological Management Avoid triggers (e.g., alcohol, temp extremes) Stress management Allergen control Gentle exercise Mast cell stabilizing supplements (quercetin, luteolin, vitamin C, vitamin D) Adequate hydration Air/water filters Trial of low-histamine diet or low FODMAP diet - * with assistance of RD, as this population may be at elevated risk for eating disorders	Non-Pharmacological Management Adequate hydration (2–3 L/day) Increased salt intake Compression garments Gradual upright training Small, frequent lower-glycemic meals Physical therapy (endurance, strength) Cooling for heat intolerance Assessment of potential reactions to caffeine, alcohol, energy drinks, high-carbohydrate meals, gluten or other potential dietary triggers* We recommend these additional tips from Standing Up to POTS	Non-Pharmacological Management Physical therapy (proprioception, joint strengthening) Low-impact exercises (swimming, yoga) Joint bracing Pain pacing Lifestyle adjustments (avoid overexertion) Address comorbidities (GI, sleep) Anti-inflammatory diet*
Pharmacological Treatment	Pharmacological Treatment H1 & H2 antihistamines (loratadine, famotidine) Low-dose naltrexone Sodium cromolyn Leukotriene receptor antagonists (montelukast) Mast cell stabilizers (cromolyn) NSAIDs or low-dose corticosteroids (if needed) Biologics (omalizumab) for severe cases	Pharmacological Treatment Beta-blockers (propranolol) for HR control Fludrocortisone for volume expansion Midodrine for low BP Ivabradine for tachycardia SSRIs or SNRIs for autonomic symptoms	Pharmacological Treatment Symptomatic treatments per comorbidities Low dose naltrexone Low-dose tricyclics or gabapentinoids for chronic pain NSAIDs for pain Muscle relaxants (e.g. cyclobenzaprine) Surgical intervention for severe joint instability (rare)
Websites for More Information	Websites for More Information Mast Cell Action	Websites for More Information Standing Up to POTS The Dysautonomia Project Dysautonomia International POTS UK Dysautonomia Support Network	Websites for More Information The Ehlers-Danlos Society Ehlers-Danlos Support UK
Podcasts with More Information	Podcasts Mast Cell Matters: Deep dives on MCAS with Tania Dempsey, MD	Podcasts The POTScast	Podcasts Bendy Bodies with Dr. Linda Bluestein
Recommended Books	Recommended Books Never Bet Against Occam by Dr. Laurence Afrin, MD Link on Amazon	Recommended Books The Dysautonomia Project: Understanding autonomic nervous system disorders Link on Amazon	Recommended Books Disjointed
Hypotheses about Relationships	Hypotheses about Relationships There are many hypotheses, including: Inflammatory mast cell mediators, when chronically released due to MCAS, may damage nerves, blood vessels, collagen or tissues Chronically heightened sympathetic activation from POTS hypoxia may help promote mast cell activation Overly stretchy blood vessels from hEDS may contribute to blood pooling exacerbating POTS More explanation of hypotheses can be found in this video by Dr. Andrew Maxwell, MD, FACC

Triad Basics

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