Allergies and Sensitivities in hEDS
See below for Difference Between MCAS and Allergies
Allergies and sensitivities are empirically more prevalent in people with hypermobile Ehlers-Danlos syndrome (hEDS) than in the general population. These may include food allergies, drug reactions, chemical sensitivities, and environmental allergies, often accompanied by skin and gastrointestinal symptoms. These reactions can be mild to severe and frequently overlap with other common hEDS complaints such as chronic pain, fatigue, and autonomic dysfunction.
Allergies vs. Sensitivities
Although people often use the words interchangeably, allergies and sensitivities are not the same.
Allergies are typically IgE-mediated, meaning the immune system produces a specific antibody (IgE) that reacts to an allergen such as pollen, peanuts, or medications. When IgE is triggered, mast cells release histamine and other chemicals, causing classic allergic symptoms like hives, swelling, sneezing, wheezing, or even anaphylaxis. Allergies can usually be confirmed with standardized tests (skin prick or blood IgE).
Sensitivities cause reproducible symptoms but are not IgE-mediated and usually do not show up on allergy tests. These include drug sensitivities, chemical sensitivities, histamine intolerance, or food intolerances such as lactose intolerance. The mechanisms vary — sometimes involving enzyme deficiencies, altered chemical processing, or other immune pathways — but they can still cause significant symptoms.
MCAS (mast cell activation syndrome) overlaps with both: it is not triggered by a specific allergen, but instead by mast cells releasing mediators inappropriately. This produces allergy-like symptoms without a clear allergen trigger and may coexist with either allergies or sensitivities.
Prevalence and Symptoms
Empirically Observed in hEDS
Higher rates of
Food allergies
Drug sensitivities
Asthma
Urticaria (hives)
Anaphylaxis
Common symptoms
Flushing, pruritus (itching)
Urticaria and angioedema (swelling, especially of the lips, eyes, or face)
Gastrointestinal issues: nausea, bloating, abdominal pain, diarrhea
Systemic symptoms: fatigue, dizziness, brain fog (may overlap with POTS or MCAS)
Respiratory: wheezing or shortness of breath
These symptoms may be episodic or chronic, and can interfere significantly with daily functioning.
Causes: Why Are Allergies and Sensitivities More Common in hEDS?
Empirically Supported Mechanisms
Strong association exists with mast cell activation disorders (MCAD), particularly mast cell activation syndrome (MCAS), with many hEDS patients meeting diagnostic or probable criteria for MCAS.
Aberrant mast cell activity occurs, where mast cells inappropriately release chemical mediators such as histamine, prostaglandins, and tryptase, leading to widespread inflammation and allergic-type symptoms.
Primary immunoglobulin deficiencies have been reported in hEDS, contributing to immune dysregulation.
Theoretical Mechanisms
Connective tissue fragility may compromise mucosal barriers (gut lining, airway lining), increasing exposure to allergens and irritants.
Chronic immune activation from biomechanical strain and tissue microinjury may lead to hypersensitivity.
Shared genetic or molecular pathways between hEDS and MCAD are suspected, though not yet fully mapped.
Autonomic dysfunction (e.g., in POTS) may intensify reactions to environmental triggers through abnormal vascular and immune signaling.
Diagnosis
Patients with hEDS and unexplained allergic symptoms should be evaluated for
Mast cell activation disorder (MCAS)
Primary immune deficiency syndromes (e.g., IgG subclass deficiencies)
According to the GeneReviews guideline from the University of Washington, clinicians should screen for Mast Cell Activation Disorders (Mast Cell Activation Disorder, Systemic Mastocytosis and other rarer diseases) and immunodeficiency in patients with recurrent allergic symptoms, frequent infections, or anaphylaxis-like episodes.
For information on anesthesia, see the separate page on Surgical Considerations.
Treatment and Management
Empirically Supported Treatments
Trigger avoidance: identify food, medication, or environmental triggers via diary tracking or specialist testing
Non-sedating antihistamines (H1 blockers) as first-line treatment (available over-the-counter)
Cetirizine (Zyrtec) – mild sedation possible in some people
Loratadine (Claritin) – generally non-sedating
Fexofenadine (Allegra) – least sedating of the group
Levocetirizine (Xyzal) – active isomer of cetirizine
Desloratadine (Clarinex) – active metabolite of loratadine
Intranasal corticosteroids (available over-the-counter) for allergic rhinitis, especially nasal congestion and seasonal/environmental allergies.
Fluticasone (Flonase, store brands) – broad anti-inflammatory effect; often considered the most effective single-agent therapy for nasal allergies.
Other options include triamcinolone (Nasacort) and budesonide (Rhinocort).
H2 blockers for additional histamine control, especially for GI symptoms (available over-the counter)
Famotidine (Pepcid and store brands at major retailers)
Leukotriene receptor antagonists (available by prescription) to address respiratory and inflammatory pathways
Montelukast
Mast cell stabilizers (available by prescription). Mast cell stabilizers are used in MCAS to prevent mast cells from releasing histamine and other mediators, especially when H1 and H2 blockers alone are insufficient. They are most helpful for gastrointestinal and systemic mast cell symptoms, require prescription, and may take time to show benefit. Unlike antihistamines (which block histamine after it is released), mast cell stabilizers act upstream by preventing mediator release.
Cromolyn sodium (Gastrocrom, oral solution). This is the form most often used in MCAS for GI and systemic symptoms.
Epinephrine autoinjector: prescribed for those at risk of anaphylaxis
Immunoglobulin replacement therapy: if a primary immunodeficiency is confirmed
Many people with hEDS find that taking an H1 blocker, famotidine, and montelukast daily helps control MCAS symptoms, although robust trial data in this specific population are limited.
Theoretical or Adjunctive Strategies
DAO enzyme supplements for suspected histamine intolerance
Low-histamine or low-salicylate diets
Gut repair protocols: probiotics, barrier support for leaky gut
Stress reduction and autonomic regulation (yoga, breathwork, pacing)
Functional medicine approaches for overlapping chemical sensitivity or immune dysregulation
Summary
People with hEDS are significantly more likely to experience allergies, sensitivities, and immunPeople with hypermobile Ehlers-Danlos syndrome (hEDS) experience higher rates of allergies, sensitivities, and immune-related reactions compared to the general population. These may include food allergies, drug sensitivities, chemical sensitivities, and environmental triggers, often with symptoms that overlap pain, fatigue, gastrointestinal dysfunction, and autonomic problems. Mechanisms are varied — from IgE-mediated allergies, to non-IgE sensitivities, to mast cell activation syndrome (MCAS) — and can make diagnosis complex.
Management usually combines trigger avoidance with treatments such as H1 and H2 antihistamines, leukotriene blockers, intranasal corticosteroids for nasal symptoms, mast cell stabilizers, and epinephrine for severe reactions. Adjunctive strategies like dietary modification, enzyme support, and autonomic regulation may also help. A multidisciplinary approach, guided by allergists, immunologists, and clinicians familiar with hEDS, is often necessary to improve quality of life and reduce the burden of symptoms.e-mediated symptoms, often due to mast cell dysfunction or immune dysregulation. These symptoms can affect multiple systems and are frequently misattributed to anxiety or unrelated disorders.
Treatment requires a multidisciplinary, individualized approach, involving allergists, immunologists, and providers familiar with hEDS, with a focus on trigger avoidance, antihistamines, and mast cell stabilization. Management should be integrated into the broader care of hEDS, as allergic symptoms can intensify pain, fatigue, GI dysfunction, and autonomic symptoms.
Difference Between MCAS, Allergies and Sensitivities
In someone with hypermobile Ehlers-Danlos syndrome (hEDS), mast cell activation syndrome (MCAS), allergies, and sensitivities can all cause overlapping symptoms — like itching, hives, flushing, stomach upset, and even breathing difficulty — but they are distinct conditions with different causes, triggers, and treatments.
Core Differences
Feature | MCAS | Allergies | Sensitivities |
What it is | Dysregulation of mast cells — overreacting inappropriately | Immune system reaction to specific allergens (e.g., pollen, peanuts, medications) | Non-IgE reactions such as drug sensitivities, chemical sensitivities, food intolerances, or histamine intolerance |
Trigger type | Often nonspecific: heat, cold, stress, scents, friction | Specific allergens like food, pollen, animal dander | Variable: foods, medications, chemicals, or high histamine load |
Immune mechanism | Mast cells release mediators without a true allergen | Usually IgE-mediated (immune antibodies drive histamine release) | Not IgE-mediated; may involve enzyme deficiencies, altered chemical processing, or other immune pathways |
Common in hEDS? | Very commonly reported; overlaps with POTS, GI issues, skin fragility | Also common, but may be separate or sometimes misdiagnosed MCAS | Frequently reported, often mislabeled as “allergy” |
Diagnosis
MCAS | Allergies | Sensitivities | |
Testing | Often difficult; labs may be normal | Standardized (skin prick or IgE blood tests) | No standardized test; usually diagnosis of exclusion plus symptom diary |
Workup | Diagnosis of exclusion or medication trial; may need tryptase, histamine, prostaglandin D2 | Positive IgE or skin test to specific allergen | Clinical history; sometimes food challenges, elimination diets, or drug re-challenges |
In hEDS Patients Specifically
MCAS | Allergies | Sensitivities | |
Symptom pattern | Widespread, fluctuating, systemic (flushing, GI upset, fatigue, anaphylaxis) | Usually tied to identifiable triggers (e.g., pollen, latex, peanuts) | Often inconsistent; symptoms reproducible but not linked to IgE (e.g., bloating from dairy, reaction to fragrances) |
Overlap | Commonly co-occurs with POTS, GI dysmotility, skin fragility | Can coexist with MCAS or sensitivities | Frequently coexists with MCAS; sometimes mistaken for allergy |
Recognition | Often mistaken for anxiety, IBS, or “functional” disorders | More likely to be recognized and diagnosed early | Often dismissed or minimized due to lack of standard testing |
Treatment Differences
MCAS | Allergies | Sensitivities | |
Approach | Combination therapy: H1 + H2 antihistamines, mast cell stabilizers (e.g., cromolyn), leukotriene blockers, low-histamine diet | Allergen avoidance, H1 antihistamines, epinephrine if anaphylaxis risk | Trigger avoidance (e.g., lactose-free diet, fragrance avoidance, low-histamine diet); sometimes enzyme replacement (e.g., lactase, DAO) |
Response | Often requires multiple meds taken regularly; trial-and-error | More predictable and testable response to treatment | Improvement depends on identifying and eliminating triggers; medications often less effective |
Summary
Allergies, sensitivities, and mast cell activation syndrome (MCAS) share overlapping symptoms but arise from different biological pathways. Allergies are usually IgE-mediated responses to specific allergens, sensitivities cause reproducible reactions without IgE involvement, and MCAS reflects inappropriate mast cell mediator release without a true allergen trigger. In hEDS, these conditions often coexist, creating complex and fluctuating symptom patterns.
Clear diagnosis is important because treatment approaches differ. Allergies respond best to allergen avoidance, antihistamines, and epinephrine when needed. Sensitivities often improve with trigger identification, dietary or lifestyle changes, and sometimes enzyme support. MCAS generally requires a multi-drug approach using combinations of antihistamines, mast cell stabilizers, and leukotriene blockers. Recognizing the distinctions between these conditions allows patients and providers to better tailor management strategies in hEDS.
