When we think of allergic reactions, we usually imagine hay fever, food allergies, or asthma triggered by pollen, peanuts, or animal hair. But what happens when someone experiences allergy-like symptoms, yet allergy tests come back negative? This Allergy Awareness Week (22–28 April), we’re joining forces with Mast Cell Action to spotlight Mast Cell Activation Syndrome (MCAS), a frequently misunderstood and under-recognised condition that often goes misdiagnosed or undiagnosed for years.
MCAS is not a typical allergy, though it shares some of the same biological mechanisms. It's a condition where mast cells, which are part of the immune system, release chemical mediators like histamine inappropriately or excessively even when there’s no allergen present.
These episodes can be triggered by everyday things: temperature changes, stress, certain foods, medications, exercise, hormones, or sometimes no clear trigger at all.
Why Mast Cell Activation Syndrome (MCAS) is often misdiagnosed
The symptoms of MCAS mimic classic allergic reactions, such as hives, swelling, anaphylaxis, itching, GI distress, which is why it’s often misdiagnosed as an allergy or overlooked entirely. Patients may go years without a clear diagnosis, especially when allergy tests come back normal. This is why raising awareness is crucial for both healthcare professionals and patients.
What do Mast Cell Activation Syndrome (MCAS) symptoms look like?
MCAS can affect multiple systems at once. Common symptoms include:
- Skin: flushing, itching, hives, swelling
- Respiratory: wheezing, throat tightness, shortness of breath
- GI: bloating, cramps, nausea, diarrhea, reflux
- Neurological: headaches, brain fog, anxiety
- Cardiovascular: rapid heartbeat, low blood pressure, fainting
- Others: fatigue, anaphylaxis, bladder or joint pain
Symptoms can wax and wane unpredictably, often worsening after stress, infection, or physical trauma.
Diagnosing Mast Cell Activation Syndrome (MCAS) and overlapping conditions
Diagnosing MCAS can be particularly challenging. Its symptoms are often widespread, fluctuating, and overlap with many other conditions, making it a diagnosis that requires clinical vigilance and a structured approach.
Key diagnostic criteria:
- Clinical symptoms
Recurrent or persistent symptoms involving two or more organ systems, such as skin, gut, respiratory, neurological, or cardiovascular. - Positive response to mast cell-targeted therapy
Improvement with medications like H1/H2 antihistamines, mast cell stabilisers, or leukotriene receptor antagonists supports the diagnosis. - Mediator tests
Elevated levels of mast cell mediators (e.g. histamine, tryptase, prostaglandins, leukotrienes) in blood or urine, ideally collected during or soon after a flare. - Exclusion of other conditions
Differential diagnosis is essential as some symptoms overlap
In cases where not all criteria are met, but the clinical picture is strongly suggestive, a diagnosis of “suspected MCAS” may be made to guide treatment while further evaluation continues.
The importance of recognising comorbidities
Adding another layer of complexity, MCAS often coexists with other chronic, multisystem conditions, many of which share overlapping symptoms. These comorbidities include: Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (PoTS), Chronic Fatigue Syndrome (CFS/ME) and Long COVID.
These conditions can all involve fatigue, cognitive dysfunction (ie brain fog), gastrointestinal issues, and autonomic dysregulation, which can mask or mimic MCAS, and vice versa. Understanding these overlaps is critical for accurate diagnosis and holistic management.
A collaborative, multidisciplinary approach can help practitioners address the full scope of a patient's experience, moving beyond symptom management to improve quality of life.
Common triggers of Mast Cell Activation Syndrome (MCAS)
- Foods (especially histamine-rich or processed foods)
- Temperature extremes
- Fragrances and chemicals
- Stress and sleep disturbance
- Hormonal shifts
- Exercise
- Medications, including excipients in medications
Practical guidance for managing MAST Cell Activation Syndrome (MCAS)
According to the Mast Cell Activation Syndrome: A Primary Care Guide there’s no one-size-fits-all treatment, but symptom management is the goal through a combination of self-care and pharmacological interventions.
While no medications are currently licensed specifically for MCAS, various medications can help stabilise mast cells and alleviate symptoms.
Treatment typically follows a stepwise approach, starting with H1 and H2 antihistamines, followed by mast cell stabilisers, leukotriene receptor antagonists, and other adjuncts as needed. Dosing is often individualised, with some patients requiring higher-than-standard doses for symptom control.
Pharmacological treatments 
Some patients may require higher-than-standard antihistamine doses, as per NICE guidelines for chronic urticaria.
Compounded medication to support patients with MAST Cell Activation Syndrome (MCAS)
Managing MCAS or histamine sensitivity can be complex, especially when excipients (inactive ingredients) in medications, such as fillers, dyes, or preservatives can trigger symptoms. While antihistamines are widely accessible over the counter, they might not be the best approach, particularly in patients requiring higher dosages or potential reactions to inactive ingredients.
To support this, Rosway Labs offers compounded medications with minimal excipients, using only the active ingredients required (some patients take a capsule with more than one ingredient) and minimum suitable fillers. This tailored approach can significantly improve tolerability and treatment success for sensitive patients.
Both MCAS and Long COVID can present with symptoms of histamine intolerance. For these patients, standard medications may contain additional ingredients eg fillers, preservatives, or dyes that provoke symptoms. Even small amounts of these additives can cause issues. At Roseway Labs, we:
- Offer compounded antihistamines with minimal fillers
- Use only the active ingredient required plus a single, well-tolerated filler or bulking agent
- Can adapt the filler to the individual needs of the patient
- Can modify the capsule shell (some contain titanium dioxide or other ingredients that are not well-tolerated)
- Can modifying the strengths of medications
This greatly reduces the risk of side effects and supports those with hypersensitive systems. We work with pharma-grade ingredients, including Famotidine, Loratadine, Ketotifen, Cetirizine and Sodium cromoglycate.
Every treatment is compounded precisely to suit the patient, offering a more personalised approach to managing complex conditions like MCAS, histamine intolerance, and Long COVID.
Roseway Labs collaborates with clinicians seeking tailored formulations for sensitive patients to help deliver optimal, patient-specific care for complex conditions.
Practical strategies for patients managing Mast Cell Activation Syndrome
Alongside medical treatment, lifestyle changes play a vital role in managing MCAS symptoms and improving overall quality of life. Patients may find the following strategies helpful in reducing flares and identifying personal triggers:
- Keep a symptom and trigger diary
- Work with clinicians to trial medications one at a time
- Avoid triggers where possible
- Explore stress reduction techniques (yoga, CBT, mindfulness)
- Consider dietary adjustments, particularly low-histamine diets with input from a knowledgeable dietitian
Education and support to improve diagnosis and patient care
By recognising the signs of MCAS and differentiating it from traditional allergies, we can improve diagnoses, patient outcomes, and quality of life.
If you’re a medical professional, we encourage you to consult the full MCAS Primary Care Guide and explore continuing education on this emerging condition using the resources and clinical insights for medical professionals on the Mast Cell Action website.
This blog was informed by the Mast Cell Activation Syndrome: A Primary Care Guide, with medical expert contributions from:
- Dr. Johanna Theron, MBChB, MSc Pain Management, PG Cert Clin Ed
- Dr. Bethan Myers, MA(Cantab), MB BCh, FRCP, FRCPath
- Dr. Jose Costa, MD FRCPCH
For more resources visit mastcellaction.org or to join the Mast Cell Action medical professional network, visit Healthcare Professionals Registration Form. If you would like more information and support on working with Roseway Labs to treat sensitive conditions like MCAS or allergies, please contact us at info@rosewaylabs.com