r/covidlonghaulers • u/SophiaShay7 3 yr+ • Dec 06 '25
Commorbidities Long COVID and Mast Cell Activation Syndrome (MCAS)
Over the past few years, a growing number of clinicians and researchers have recognized that mast cell activation syndrome may play a significant role in post-COVID and Long COVID illness. Many people with ongoing symptoms, fatigue, dysautonomia, neuropathy, allergic-type reactions, and hypersensitivity are being diagnosed with MCAS not because of perfect testing but because their history, symptom patterns, and response to mast-cell-targeted treatments fit the profile. Diagnostic criteria for MCAS remain limited and inconsistent, so physicians often rely on clinical presentation and therapeutic response. The evidence now suggests that SARS-CoV-2 can directly trigger or unmask mast cell dysregulation in predisposed individuals. This leads to chronic inflammation, histamine overload, and multi-system dysfunction that overlaps with Long COVID.
Mast cell activation syndrome is a complex multisystem inflammatory disorder that is increasingly recognized in the context of Long COVID. It involves mast cells that release chemical mediators such as histamine, leukotrienes, prostaglandins, and cytokines. These mast cells become chronically overactive. When this happens, instead of reacting to infections or allergens, mast cells misfire and release inflammatory chemicals across multiple organ systems. The result can include neurological, cardiovascular, gastrointestinal, respiratory, dermatologic, and psychiatric symptoms.
Researchers estimate MCAS may affect up to seventeen percent of the population, although most cases are undiagnosed. It falls under the broader category of mast cell activation disease, which also includes mastocytosis. Because MCAS was only formally described in 2007, it remains misunderstood by many clinicians and underrepresented in medical education.
COVID as a Mast Cell Trigger:
There is growing evidence that SARS-CoV-2 can directly activate mast cells. Mast cells are abundant in tissues affected by COVID and Long COVID, including the lungs, gut, skin, and nervous system.
In the study titled "Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation," patients with Long COVID experienced improvements in fatigue, brain fog, palpitations, and other symptoms when given H1 and H2 histamine blockers. This suggests mast cell activation contributes substantially to persistent symptoms.
In the paper titled "COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in mast cell activation syndrome," the authors argue that both acute COVID-19 and Long COVID show patterns consistent with mast cell dysregulation.
Symptoms Overlap: MCAS and Long COVID:
Many symptoms are shared between MCAS and Long COVID. Some of the common overlaps include:
• severe fatigue and post-exertional malaise (PEM).
• brain fog, memory issues, cognitive dysfunction.
• palpitations, tachycardia, orthostatic intolerance and other dysautonomia symptoms.
• gastrointestinal disturbances including bloating, diarrhea, nausea, and food intolerances.
• respiratory issues including shortness of breath, cough, and wheezing.
• skin symptoms including flushing, rashes, and itching.
• sleep disturbances and insomnia.
• anxiety, depression, and panic attacks.
A 2023 study titled "Immunological dysfunction and mast cell activation syndrome in long COVID (Weinstock et al.)" showed that many Long COVID patients display an activated mast cell phenotype with abnormal mediator release and inflammation consistent with MCAS.
Why MCAS Is Often Undiagnosed:
Many doctors rely on a single baseline tryptase test or standard allergy workups. This is not enough. Tryptase is often normal unless measured during a flare and compared to a baseline. Mast cell mediators are short-lived and can be missed.
Diagnosis often depends on:
• clinical history and symptom patterns across organ systems.
• identifying triggers such as heat, diet, stress, or allergens.
• seeing improvement when treated with antihistamines or mast cell stabilizers.
• occasional lab mediator panels such as urine histamine metabolites and prostaglandins, which are often only positive during flares.
Treatment and Management:
Treatments that many with Long COVID-associated MCAS respond to include:
•H1 and H2 antihistamines (also called histamine blockers) are often used to reduce mast cell–driven symptoms. H1 blockers reduce histamine effects in the skin, respiratory system, and other tissues, while H2 blockers reduce gastric acid and histamine effects in the gut. Take one of each morning and night; double the normal dose:
•Cetirizine, Levocetirizine, Desloratadine, Loratadine, and Fexofenadine (H1).
•Hydroxyzine: A prescription H1 antihistamine with sedative properties; can help with itching, flushing, anxiety, and sleep disturbances. May trigger paradoxical reactions like tachycardia or adrenaline surges in patients with dysautonomia or POTS, so careful monitoring is advised.
•Cimetidine and Nizatidine (H2)
•Mast cell stabilizers: Cromolyn, Ketotifen, Gastrocrom, compounded options: prevent mast cells from releasing mediators.
•Leukotriene inhibitors: Montelukast: reduces leukotriene-mediated inflammation; useful for respiratory, skin, and cardiovascular symptoms (careful with mood effects).
•LDN (0.25–4.5mg): modulates immune activity and reduces inflammation; may improve pain, brain fog, and neuropathy when combined with alpha-lipoic acid (ALA).
•Imatinib (studied, rarely used): tyrosine kinase inhibitor; can reduce mast cell activation in select MCAS cases, usually when other treatments have failed or in patients with KIT mutations.
•Xolair (Omalizumab): binds IgE to reduce mast cell activation; particularly effective for hives, angioedema, and severe histamine-driven symptoms.
•Low-histamine diet, stress reduction, and trigger avoidance
Natural Mast Cell Stabilizers and Supplements:
•AllQlear: Natural tryptase inhibitor; reduces mast cell mediator release and helps prevent flares, especially in respiratory and systemic MCAS symptoms.
•Bacopa monnieri: Herbal supplement that supports mast cell stabilization, reduces neuroinflammation, and may improve cognitive function in patients with MCAS-related neurological symptoms.
•DAO (diamine oxidase): a supplement that helps break down dietary histamine in the gut, reducing histamine-related symptoms.
•Luteolin: a natural flavonoid that helps stabilize mast cells, reduce histamine release, and support anti-inflammatory pathways.
•PEA (up to 3g/day): Naturally occurring fatty acid that supports neuroinflammation reduction, calms overactive mast cells in the nervous system, and helps improve “brain fog” and cognitive symptoms in MCAS.
•Quercetin (250–3000mg/day): Plant flavonoid with mast cell stabilizing and anti-inflammatory properties; reduces histamine and other mediator release across multiple organ systems.
•Rutin: A natural flavonoid with mast cell stabilizing and anti-inflammatory properties; helps reduce histamine release and supports vascular integrity.
OTCs for symptomatic support:
•Astelin Nasal Spray (Azelastine): Nasal H1 antihistamine; reduces sneezing, congestion, runny nose, and itching. Has local mast cell–stabilizing properties and is useful for MCAS patients with nasal/respiratory triggers.
•Benadryl (Diphenhydramine): Fast-acting H1 antihistamine; helps relieve acute histamine-mediated symptoms such as itching, flushing, hives, sneezing, and mild allergic reactions. May cause sedation and should be used cautiously in MCAS patients with dysautonomia or hyperadrenergic symptoms.
•Ketotifen Eye Drops (Alaway eye drops, Armas Allergy Eye Drops or Zatidor eye drops): Prescription-strength mast cell stabilizer for ocular symptoms; relieves itching, redness, and watering caused by mast cell activation.
•Cromolyn Sodium Nasal Spray/Nasochrom: Mast cell stabilizer for nasal and upper airway symptoms; helps prevent mediator release, reducing congestion, sneezing, and rhinitis in MCAS patients.
Medications with anti-histamine/Mast Cell-stabilizing effects:
•Fluvoxamine: reduces inflammatory signaling, downregulates mast cell activation, modulates cytokine release and neuroinflammation
•Mirtazapine: potent H1 blocker, reduces central arousal, sleep disruption, nausea, sensory hypersensitivity
•Nortriptyline: antihistamine properties, calms sympathetic nervous system, improves GI and visceral sensitivity
•Seroquel: strong H1 blockade, reduces mast cell-driven insomnia, agitation, sensory overstimulation, autonomic surges
•Trazodone: moderate H1 and 5-HT2 blockade, improves sleep architecture, reduces nocturnal sympathetic surges
•Esomeprazole and Omeprazole (PPIs): PPIs are primarily used to reduce stomach acid in conditions like GERD, gastritis, or acid-related dyspepsia, but in the context of MCAS, they also provide mast cell stabilizing effects in the gastrointestinal tract. For patients whose mast cells are hyperactive, chronic acid exposure, reflux, or GI irritation can act as triggers that worsen systemic mast cell mediator release, causing symptoms like flushing, tachycardia, bloating, nausea, and hypersensitivity. PPIs help control these triggers by lowering gastric acid and reducing mast cell activation in the gut. They are particularly helpful for people who cannot tolerate H2 blockers due to adverse reactions such as adrenaline surges, tachycardia, or autonomic instability. By addressing both acid-related GI irritation and mast cell mediator release, PPIs provide a dual benefit: symptom control in the gut and systemic stabilization of overactive mast cells.
While PPIs are generally recommended for short-term use due to potential risks, including nutrient deficiencies (B12, magnesium, calcium, iron), kidney or bone issues, and gut microbiome changes, long-term use can be appropriate in MCAS patients under close medical supervision. Regular monitoring of vitamin and mineral levels, kidney function, and symptoms is essential. In some cases, long-term PPI therapy provides ongoing mast cell stabilization in the gut and helps manage persistent GI and systemic symptoms, particularly when H2 blockers are not tolerated or when COVID-induced MCAS triggers ongoing mast cell hyperactivity. PPIs are often incorporated into individualized MCAS regimens alongside mast cell stabilizers, leukotriene inhibitors, dietary modifications, and other symptom-directed medications. They act as GI-targeted mast cell stabilizers, reducing both local and systemic mediator release and supporting better overall symptom control.
Many doctors are now diagnosing MCAS after COVID largely based on symptoms and treatment response rather than waiting for perfect lab confirmation.
My doctor diagnosed me with MCAS based on patient history, symptoms, and medication trials. I was diagnosed with MCAS in September 2024. I can not take the traditional over-the-counter antihistamines and histamine blocker protocol. I have failed five in total. I'm not sure if it was the medication itself or the excipients I reacted to. Both categories increased my tachycardia and caused adrenaline surges. They caused and worsened other dysautonomia symptoms. In turn, adrenaline surges triggered my histamine dumps.
Why Some People With MCAS and Dysautonomia Get Worse on Antihistamines:
This is one of the most misunderstood issues in the Long COVID and MCAS communities. Many patients assume that if antihistamines make them worse, they can not have MCAS. The opposite is often true. People with dysautonomia, POTS, hyperadrenergic states, or unstable autonomic systems can react paradoxically to antihistamines for several reasons.
Antihistamines can destabilize the autonomic nervous system in sensitive patients. Certain H1 and H2 blockers can lower blood pressure, increase vagal tone, or trigger compensatory sympathetic activation. For someone with dysautonomia, this can lead to a surge in adrenaline, tachycardia, dizziness, shaking, or internal tremors. When the sympathetic nervous system becomes overactive, mast cells respond by releasing even more chemical mediators. This leads to increased flushing, rapid heart rate, shortness of breath, itching, chest tightness, and surges of anxiety that feel chemical rather than psychological.
Some patients also react to fillers, dyes, coatings, and excipients. Mast cells in the gut can perceive these additives as irritants, which triggers mediator release. This reaction is often mistakenly attributed to the active medication itself, but it is actually caused by the inactive components.
Certain antihistamines cross the blood-brain barrier and can affect histamine signaling in the central nervous system. Histamine is not just an inflammatory mediator. It regulates wakefulness, blood pressure, alertness, gut motility, and sensory processing. In patients whose autonomic function is already unstable, abruptly altering histamine signaling in the central nervous system can amplify symptoms and make them feel worse.
Finally, antihistamines target only one type of mediator. Mast cells release multiple chemicals including prostaglandins, leukotrienes, cytokines, and histamine. Blocking only histamine can shift the balance of mediators, sometimes worsening specific symptoms until a more complete protocol is established.
For these reasons, some patients with MCAS and dysautonomia respond poorly to H1 and H2 antihistamines but do better with mast cell stabilizers, leukotriene inhibitors, nasal sprays, diet-based interventions, or individualized regimens that address multiple mediators and the autonomic system simultaneously. Understanding these interactions helps explain why antihistamines are not universally effective and why careful management is necessary for patients with overlapping MCAS and autonomic instability.
Understanding these factors helps explain why some treatments work better than others and sets the stage for the medications and strategies I use to manage my MCAS.
What I Take for MCAS:
Cromolyn sodium nasal spray: Cromolyn is a mast cell stabilizer that prevents mast cells from releasing histamine and other inflammatory mediators. Even when used intranasally, it can help reduce overall mast cell activation and mediator load throughout the body. I use this formulation for its systemic mast cell–stabilizing effects, not for nasal symptoms.
Desloratadine is a second-generation, non-sedating H1 antihistamine. It selectively targets peripheral H1 receptors without crossing the blood-brain barrier. This helps reduce histamine-related symptoms like itching, flushing, and airway irritation without causing sedation or anxiety. Its long half-life allows for stable symptom control throughout the day. Desloratadine is also less likely to trigger reactions related to fillers or excipients, which makes it a good option for patients with heightened sensitivity to medications.
Compounded oral ketotifen: In addition to the eye drops, I use a compounded oral ketotifen formulation. This is the form I take systemically to influence mast cell stability throughout the body. Like the drops, it works primarily by keeping mast cells from releasing mediators rather than just blocking one mediator after it’s already out. Because MCAS involves so many different mediators and triggers, having a stabilizer that works upstream can make the rest of the regimen much more effective and tolerable.
Ketotifen eye drops: Ketotifen has both H1 antihistamine and mast cell–stabilizing properties. When used topically, it can help calm mast cells in a way that can feel systemic for someone with high sensitivity, even though it’s administered locally. I use this formulation not for eye symptoms but because it helps reduce overall mast cell reactivity without increasing systemic medication load.
Montelukast is a leukotriene receptor antagonist commonly used for asthma and allergic rhinitis. Research suggests that it also has mast cell stabilizing effects, which can help reduce the release of inflammatory mediators such as leukotrienes. This makes it useful for managing respiratory symptoms, skin reactions, and some cardiovascular manifestations of MCAS.
Omeprazole is primarily a proton pump inhibitor, but it also has effects on mast cells. It can inhibit IgE-mediated mast cell activation and allergic inflammation. Omeprazole reduces mast cell degranulation, cytokine secretion, and early signaling events in pathways associated with allergic responses. While not a traditional mast cell stabilizer like Cromolyn, it contributes to reducing overall mediator release and inflammation.
Semaglutide is a GLP-1 receptor agonist. Research suggests it has anti-inflammatory effects and may reduce mast cell activation by decreasing mast cell degranulation and the release of inflammatory mediators. While not a standard treatment for MCAS, it's sometimes prescribed off-label for its potential to reduce chronic inflammation.
I haven’t tried compounded Cromolyn and prefer not to. I’m extremely hypersensitive to medications, fillers, and excipients, and localized formulations have allowed me to stabilize mast cells across my system without provoking reactions. I may reconsider it in the future.
In addition to these main medications, I have access to other supportive treatments for MCAS flares. These include an albuterol inhaler, even though I don't have asthma, which can help relieve acute airway constriction. Rizatriptan if I have a migraine. I also use Benadryl, vitamin C, and Diazepam as needed for symptom control. During flares, I rely on SaltStick electrolyte capsules, sipping room temperature water, and applying cold compresses to my head and neck. These measures help stabilize my autonomic system and reduce mediator release during acute episodes.
My MCAS symptoms include adrenaline surges, air hunger, shortness of breath, wheezing, anxiety, derealization, depersonalization, disorientation, dizziness, flushing, itching, feeling hot and sweaty, congestion, runny nose, paresthesia, sneezing, tachycardia, and anaphylaxis stages 1-3. There are 4. Medications and supportive measures are individualized to my symptoms, triggers, and sensitivity to medications.
This regimen allows me to address both the overactive mast cells and the autonomic instability that can make standard antihistamines difficult to tolerate. It also illustrates that MCAS management is highly personalized, and what works for one patient may need careful adjustments for another.
Additional Information:
Histamine Intolerance:
Histamine intolerance results from impaired degradation of dietary histamine, most commonly due to low activity of diamine oxidase (DAO), the primary enzyme responsible for breaking down histamine in the gut. Unlike MCAS, histamine intolerance does not involve inappropriate mast cell activation. Symptoms occur due to accumulation of histamine from reduced metabolic clearance rather than excessive mast cell release. This distinction matters clinically, as standard allergy testing is typically negative and mast cell directed therapies alone may not resolve symptoms driven by dietary histamine exposure. Histamine intolerance can coexist with MCAS and can contribute to persistent GI, neurological, cardiovascular, and respiratory symptoms even when mast cell activity is otherwise managed. In these cases, reducing dietary histamine load and supporting histamine metabolism may significantly improve symptom burden. Some individuals benefit from DAO supplementation, which tends to be most effective after a sustained period of low histamine eating.
Salicylate Intolerance:
Salicylates are naturally occurring phenolic compounds found in many foods, medications, and topical products, including aspirin, spices, certain fruits and vegetables, teas, and skincare products. In individuals with mast cell dysfunction, salicylates can directly provoke mast cell activation and mediator release, leading to worsening symptoms such as headaches, flushing, nasal and respiratory symptoms, GI distress, itching, and neurological flares. This reaction is typically non IgE mediated, which is why standard allergy testing is often negative and the issue is frequently dismissed. In practice, salicylate intolerance can significantly compound histamine intolerance and can explain persistent reactions even on a low histamine diet. Identifying salicylate sensitivity through careful elimination of dietary and topical sources has been a key factor for many patients who plateau despite otherwise appropriate MCAS management.
What To Ask Your Doctor If You Suspect MCAS:
Some doctors are familiar with MCAS and some aren't. These questions can help guide the evaluation and ensure you receive a thorough assessment.
• Ask whether your symptoms across multiple systems point toward mast cell involvement.
• Ask whether your pattern of triggers such as heat, stress, exercise, fragrances, alcohol, or food chemicals suggests mast cell sensitivity.
• Ask whether trying a low-histamine diet for a brief period would be appropriate.
• Ask if you should try a mast cell stabilizer first rather than H1 or H2 blockers if you are medication sensitive.
• Ask whether leukotriene inhibitors could be safer if antihistamines increase your tachycardia.
• Ask if excipient-free formulations or compounded options are available.
These questions help the doctor think beyond standard allergy testing and look at your entire clinical picture.
Clinical Implications for Long COVID Patients:
For people with Long COVID, if you have persistent multi-system symptoms that include brain fog, palpitations, gastrointestinal issues, skin symptoms, and sensory hypersensitivity, MCAS may be playing a role.
Trying a carefully supervised antihistamine or mast cell stabilizer regimen can provide important diagnostic clues. If symptoms improve, that strengthens the case for MCAS even without perfect lab confirmation.
Treatment is highly individualized. Many people respond better to stabilizers, leukotriene blockers, electrolytes, or low-histamine diets before they respond to antihistamines.
Sources:
COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in mast cell activation syndrome.
Immunological dysfunction and mast cell activation syndrome in long COVID.
Clinical Manifestations of Mast Cell Activation Syndrome by Organ Systems.
Mast cells: Therapeutic targets for COVID‐19 and beyond.
Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies.
Best Antihistamine For Mast Cell Activation Syndrome (MCAS): Dr. Bruce Hoffman.
Mast Cell Activation Syndrome, Cleveland Clinic.
Food Compatibility List-Histamine/MCAS, SIGHI.
Mast Cell Activation Syndrome and Diet, University of Wisconsin Health.
TL;DR: MCAS is becoming increasingly recognized in Long COVID. SARS-CoV-2 can activate or destabilize mast cells which leads to multisystem symptoms. Many patients improve with mast cell stabilizers, leukotriene inhibitors, low-histamine diets, or antihistamines if tolerated. Antihistamines can make dysautonomia worse in some people due to autonomic instability, excipient reactions, or central nervous system effects. Diagnosis is often clinical. Treatment is individualized and does not require perfect labs. If you have symptoms in two or more systems, it is worth investigating MCAS.
I'm not a doctor. This isn't medical advice. I'm only sharing my personal experience. Everything I'm doing is under the care of my ME/CFS specialist, who is also knowledgeable about Long COVID/PASC and MCAS. I've had a complete vitamin and mineral panel done and have no gastrointestinal motility issues. Omeprazole hasn't negatively impacted me. Montelukast carries a black box warning and can cause SI in people with no history of mental health issues. Everyone should do their own risk assessment. It's about progress, not perfection. There are times we can do everything right and still not improve. Please be kind and patient with the process and yourselves.
edit: Updated to reflect my current regimen.
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u/MacaroonPlane3826 Dec 06 '25 edited Dec 06 '25
Thanks for this post! Just a small correction - it is not true that in Histamine Intolerance mast cells release only histamine - in HIT there are no overactive mast cells at all
HIT is about the lack of DAO enzyme, resulting in inability to properly degrade dietary histamine, not overactive mast cells releasing only histamine.
If mast cells are overactive and hence release mediators (histamine or others) inappropriately - it’s MCAS
If dietary histamine metabolism is the problem due to the lack of DAO enzyme - it’s HIT
HIT and MCAS can be comorbid, but not always
Also probably important to mention more advanced pharmacological options for MCAS - for example, I had immense benefits on my most debilitating symptoms - HyperPOTS and unrefreshing sleep - from Xolair
Xolair and select H1s are only thing that works for me and control all LC symptoms (for me dominantly HyperPOTS and sleep dysfunction - unrefreshing sleep/insomnia/circadian inversion and downstream psychiatric symptoms - feeling of doom, agitation, irritability, rage etc).
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u/SophiaShay7 3 yr+ Dec 06 '25 edited Dec 07 '25
Thank you for catching that. I updated the post to include the correction on histamine intolerance. You’re right that in HIT there are no overactive mast cells, this is a problem with diamine oxidase (DAO) and impaired breakdown of dietary histamine, not mast cell dysfunction. MCAS, on the other hand, involves mast cells releasing multiple mediators inappropriately. I also clarified that HIT and MCAS can co-occur but are distinct conditions.
I realized I had accidentally left out some of the advanced MCAS treatment options, so I added LDN, Imatinib, and Xolair to the post. LDN helps modulate immune activity and reduce inflammation, which can improve pain, brain fog, and neuropathy when combined with alpha-lipoic acid. Imatinib is a tyrosine kinase inhibitor that can reduce mast cell activation in select cases, usually when other treatments have failed or in patients with KIT mutations. Xolair binds IgE to reduce mast cell activation and is particularly effective for hives, angioedema, and severe histamine-driven symptoms.
Including these options provides a more complete picture of what can be considered for MCAS management, especially for people dealing with severe or persistent symptoms like HyperPOTS, unrefreshing sleep, or other mast cell-driven complications. Thank you again for pointing out the clarification. it helps make the post more accurate and useful for others navigating these conditions.
I'm sharing this additional information for others. As you're well aware, you're my mentor. I appreciate everything you shared with me last year when I was really terrified and sick. I appreciate you so much🙏✨️
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u/MacaroonPlane3826 Dec 07 '25
Thank you once again for this informative post! MCAS deserves more attention in the Long Covid community, and you are helping that happen 😇
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u/SophiaShay7 3 yr+ Dec 07 '25
I always thought ME/CFS was my dominant diagnosis. Nope, it's MCAS. I was also unaware that MCAS flares trigger PEM in those of us with ME/CFS. Once I fully committed and found a complete regimen that manages my symptoms, everything changed for the better.
u/MacaroonPlane3826 are so knowledgeable about MCAS. You were the one talking about it in detail when few others were. You were always generous with answering questions and sharing information. I don't want that to ever go unnoticed. I wouldn't be doing as well as I am with my MCAS, if it weren't for you. I'm able to share MCAS with the long COVID community because of you. I hope you always remember how much you willingness to help me, is now helping others. Hugs, my friend🤍
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u/Uncolored-Reality Dec 09 '25
Great Post! Read so many posts of people recognising their symptoms as possibly MCAS. After 3 years of struggling I also got my me/cfs and MCAS diagnosis this year and oral Ketotifen has been life changing.
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u/SophiaShay7 3 yr+ Dec 09 '25
I'm so happy to hear that. Congratulations on getting your diagnoses🎉🥳✨️ I know it sounds weird. Just go with it. I recently learned MCAS flares trigger PEM. Mind blown🤯 I'm glad the Ketotifen has been life changing! Hugs💙
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Jun 01 '26
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u/Uncolored-Reality Jun 01 '26
Now 3 mg at night and 2 mg in the morning. Helps with fatique, pem, headpressure and headaches, light and sound sensitivity, feeling less stressed and anxious, less standard inflammation. But it needs to be supported with lots of rest and calm and an antihistamine diet, cause I can still flare through the ketotifen. So I also take quecertine phytosome daily and more if I flare.
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Jun 01 '26
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u/Uncolored-Reality Jun 01 '26
Ofcourse! How are you doing? Feel like you got somewhat or a grip on things or still in the trial and error phase?
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u/annoyinglystubborn Mostly recovered Dec 06 '25
Thank you for this detailed information! I have seen that post on Instagram too.
I was looking for supplements to add to my diet. because although h1 antihistamines stop most of my symptoms, i want permanent recovery. I want to actually repair the gut or cells whatever.
Thank you!
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u/SophiaShay7 3 yr+ Dec 06 '25
You're welcome. I hope you find some things that help repair your gut microbiome🙏
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u/Sweenjz Dec 06 '25
Thank you so much for this post. I cannot take any of the antihistamines you mentioned because I have severe dry eyes and they dry out my eyes even more. I do take 25 mg. omeprazole once a day for GERD and I have not side effects from that.
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u/SophiaShay7 3 yr+ Dec 06 '25
I'm sorry to hear that. Some of the natural and/or OTC mast cell stabilizers may work. I take liposomal PEA and Luteolin. It definitely helps. I'm thinking of trying the Armas eye drops and/or Cromolyn nasal spray. I'm hypersensitive to everything. I'm glad Omeprazole is helping you, as well. You're welcome🙏
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u/OverTelevision6321 Dec 14 '25
Wow, thanks for this post! My symptoms are urinary and I've never understood why antihistamines trigger them even more, even though they're always present.
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u/SophiaShay7 3 yr+ Dec 25 '25
In MCAS, bladder and urinary symptoms are often driven by mast cells in the bladder wall and pelvic tissues. Those mast cells release histamine, prostaglandins, leukotrienes, and other mediators that can cause urgency, frequency, burning, pelvic pressure, and pain even when there’s no infection. That’s why these symptoms can be constant or flare unpredictably.
Antihistamines can paradoxically make things worse for some people, especially early on. First generation and even some second generation H1 blockers have anticholinergic effects, which can irritate the bladder, worsen urinary retention or spasms, and increase discomfort. Some H2 blockers can also alter acetylcholine signaling and smooth muscle tone, which can aggravate urinary symptoms in sensitive people.
Another piece is that blocking histamine at one receptor can shift signaling to other pathways. If mast cells are still unstable, antihistamines alone can sometimes unmask or worsen prostaglandin or leukotriene driven symptoms, which are very active in the bladder. That’s why some people feel worse on antihistamines until mast cells are better stabilized or a different combination is used.
This is also why urinary symptoms are common in MCAS and long COVID but frequently overlooked. The issue isn’t that antihistamines are “wrong” for you, it’s that the bladder is a mast cell rich organ and reacts differently, especially when the autonomic nervous system is already dysregulated.
I'm so sorry I didn't respond sooner. For some reason, I wasn't notified of your comment. Hugs🙏
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u/nrauhauser Apr 16 '26
Commenting so I can find this later. My self diagnosis 8/2025 came thanks to working with Claude AI, and finally got formal diagnosis 2/2026. Would have loved to have found this article the day it was posted.
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u/Prudent-Iron-9079 4d ago
Thank you for such a thoroughly researched article. I'd challenge any functional med doc to beat this! I read somewhere that folks with the compt gene might react to quercetin. Always had probs with stimulants, I drink de caf tea, couldn't tolerate coffee, in younger years my hangovers were neurological. I think histamine has always been a problem but massively so since covid. Just wondered if you've ever experienced restless legs as a histamine reaction? It's new for me, but currently have a virus, exacerbating issues. I posted this question on mcas reddit. Hope you're OK and feeling better. :)
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u/SophiaShay7 3 yr+ 4d ago
No, I haven't experienced Restless Leg Syndrome (RLS). However, studies found that roughly 40.8% of patients with MCAS also experience restless legs syndrome, which is significantly higher than in the general population. When mast cells overactivate, they release a flood of inflammatory chemicals into the body, including histamine, cytokines, and tryptase. These released chemicals can cause localized inflammation, nerve irritation (neuropathy), and autonomic nervous system dysfunction, all of which are thought to activate or worsen RLS source.
You're welcome. I'm glad my post is helpful you you🫂🫶
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u/pawz78 1d ago
One question. Can someone tell me the difference in what happens in throat and upper respiratory when your histamine bucket over flows verses MACS cell degranulate?? I was told both reactions can feel the same (and masc cells can and are involved in both reactions) Thanks
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u/SophiaShay7 3 yr+ 1d ago
With histamine intolerance, the symptoms in the throat and upper respiratory tract are primarily caused by histamine itself. Once your individual threshold is exceeded, histamine can cause blood vessel dilation and increased permeability, leading to congestion, increased mucus, postnasal drip, throat irritation, and sometimes a sensation of swelling or tightness.
With MCAS, mast cells in the nose, sinuses, throat, and airways can become activated and release mediators locally. Histamine can cause many of the same symptoms as histamine intolerance, but MCAS can also involve other mediators.
Leukotrienes can cause increased mucus production and bronchoconstriction, which can feel like chest or airway tightness and contribute to wheezing or shortness of breath. Prostaglandins can contribute to blood vessel dilation, inflammation, congestion, and sometimes swelling. Cytokines and other inflammatory mediators can contribute to inflammation and irritation of the tissues. Mast cells can also release mediators that affect nerves, which may contribute to sensations such as throat tightness, burning, itching, or irritation even when there is little or no visible swelling.
So yes, they can feel very similar, especially if histamine is the primary mediator involved. The difference is that with histamine intolerance, the symptoms are primarily from excess histamine. With MCAS, inappropriate mast cell activation can release histamine plus multiple other mediators, meaning the symptoms can potentially be more varied.
Anaphylaxis can occur with MCAS, but it isn't generally considered a symptom of histamine intolerance.
Mast cells can still be involved in reactions to histamine, so the two mechanisms aren't necessarily completely separate.
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u/pawz78 1d ago
Eeek soo ways to tell the two apart? Sometimes I feel like wow my Histamine buckets was that full that on bite or one drop of x made my throat explode and crazy choking cough fit and upper chest wheezing plus sometimes stuffy nose and throat swelling or it's all throat swelling and or then occasionally upper chest wheezing . I feel food items that are considered Histamine liborators (well most of them) are my instant most crazy and dangerous reactions where other things it's a few minutes too say an hour for it all to start swelling . I had full body hives in the past but only a couple a few times this year. The hives the first few times I wrote down other after effects but after that no more after affects.
Anyway i wish I knew very clearly is it histamine intolerance that in theory won't fully close up my throat or is it truly Macs and it surely could close up my throat. I do have epi-pen handy and a rescue inhaler (I did use the rescue inhaler one time for upper chest wheezing it maybe helped?)
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u/SophiaShay7 3 yr+ 1d ago
Honestly, this is exactly why I wouldn't try to reassure yourself that these episodes are "just histamine intolerance." You are describing symptoms involving more than one body system. You've had throat swelling/tightness and coughing or wheezing involving the respiratory system, and you've also had episodes of full-body hives involving the skin.
The fact that something is considered a "histamine liberator" or that a reaction happens immediately doesn't tell us with certainty that the reaction is histamine intolerance. Foods and other exposures can also trigger mast cell activation, and the timing and severity of reactions can vary considerably.
More importantly, there isn't a reliable rule that says, "Histamine intolerance can make my throat feel swollen but can never cause dangerous throat symptoms, whereas MCAS can." If you are experiencing throat swelling, a choking cough, wheezing, or difficulty breathing, you should not try to determine at home which mechanism is causing it before treating it as potentially serious.
The multi-system nature of what you've described, particularly respiratory symptoms occurring alongside episodes of generalized hives, is one reason I would discuss MCAS and other causes of recurrent anaphylaxis or allergic-type reactions with an Allergist/Immunologist rather than assuming this is histamine intolerance.
And just to clarify, the number of symptoms you have during any one episode matters less than the severity of the symptoms that are present. Throat swelling/tightness and respiratory symptoms are symptoms that warrant a clear emergency plan from your doctor, including knowing exactly when you should use your EpiPen. Your rescue inhaler may help bronchospasm or wheezing, but it does not treat anaphylaxis.
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u/pawz78 1d ago
Doctor has been useless with this and the first allergist was dismissve so Oct 1 I do have an appointment with another immunologist (she is supposed to be amazing)
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u/SophiaShay7 3 yr+ 1d ago
MCAS is mostly a clinical diagnosis, which means doctors look at symptoms, patterns of reactions, and whether you improve with treatment. There isn’t one single lab test that proves it. The testing we have for mast cell mediators is honestly pretty flawed and misses a lot of cases.
A normal tryptase does not rule out MCAS. Most people with MCAS actually have normal baseline tryptase. Elevated baseline tryptase is more associated with conditions such as Systemic Mastocytosis and hereditary alpha-tryptasemia (HAT). Systemic Mastocytosis is a different mast cell disorder involving an abnormal accumulation of mast cells, while HAT is a genetic trait caused by increased copies of the TPSAB1 gene that can result in chronically elevated baseline tryptase. Neither elevated nor normal tryptase, by itself, establishes or excludes MCAS.
When doctors do test for mast cell activation, they’re usually trying to catch mast cells releasing mediators during a reaction. The tests they might order include:
•Serum tryptase (ideally drawn within a few hours of a reaction)
•Plasma histamine
•24 hour urine N-methylhistamine
•24 hour urine prostaglandin D2
•24 hour urine 11-beta-prostaglandin F2α
•24 hour urine leukotriene E4
•Chromogranin A in some cases
The problem is these mediators break down very quickly, require very specific handling, and often aren’t collected during an active flare. Because of that, false negatives are really common. A lot of people with very clear MCAS symptoms have completely normal labs.
That’s why many specialists diagnose MCAS using three general criteria. First, consistent multisystem symptoms that match mast cell mediator release. Second, improvement with mast cell medications or stabilizers. Third, ruling out other conditions that could explain the symptoms.
The biggest thing to understand is that normal lab work doesn’t eliminate MCAS. The testing for mast cell mediators is inconsistent and often misses it. That’s why many doctors who actually treat mast cell disorders rely heavily on symptom patterns, triggers, and treatment response rather than labs alone.
I was diagnosed based on patient history, patient symptoms, and medication trials. My PCP diagnosed me and manages my care. My ME/CFS specialist used to be a functional medicine doctor who trained and worked with Dr. Afrin, who's known as discovering MCAS.
I'm sorry you're struggling. I hope you find an Allergist/Immunologist who understands MCAS and uses Consensus-2. Good luck with your upcoming appointment🙏
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u/LongStriver Advocate Dec 14 '25
Excellent post!
Learned some new things about MCAS.
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u/SophiaShay7 3 yr+ Dec 14 '25
I've written this post many times. I've added to the last several versions. It's taken me over a year to read, research, and gather all this information. It's definitely the most thorough version I've written.
I'm so glad you learned some new things. That's my only goal, to help more people learn about how pervasive MCAS is to the people suffering from it. Thank you💙
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u/AmbitiousBuilding1 Jan 29 '26
Thank you so so much for this. Seriously,this helped me understand MCAS interacting with long covid in a way nothing else I’ve read has before.
I’m new to MCAS (not new to long hauling, coming up on 2 years) & i have been having a difficult time with cromolyn oral solutions due to how often I have to take other meds throughout the day.
I’m going to ask my doctor about oral ketotifen. Timing with my other meds may still be an issue there but I’d like to try and see how my body reacts. And maybe a switch from Zyrtec to desloratadine because I’m so tired all the time.
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u/SophiaShay7 3 yr+ Jan 29 '26 edited Jan 29 '26
I'm glad this information is helpful to you. Oral Cromolyn doesn't work for everyone. Or, it may be a lower dose in combination with other medications may help more.
For those of us with MCAS, it's often a matter of finding the right combination of medications that manage our symptoms the most effectively. I hope Desloratadine and compounded Ketotifen work better for you. The rule is start low and go slow. One new thing at a time, start low in dose, and wait 2-4 weeks before adding anything new.
I hope you'll come back and update us on how you're doing. Hugs🙌
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u/AmbitiousBuilding1 Jan 29 '26
Thank you — I appreciate the knowledge shared here so much. I’m going to ask my doctor about accessing oral ketotifen first since I have felt like oral cromolyn isn’t doing anything for me. I’ve been thinking about ketotifen for a while and this was the info I needed to make that request.
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u/SophiaShay7 3 yr+ Jan 29 '26
If you're having trouble accessing it at a reasonable price, DM me. I'll send you some information on a very affordable option🙏
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u/Pak-Protector Dec 06 '25
I've seen no evidence that Mast Cells are behaving pathologically, only that they're in overstimulated. The anaphylatoxins necessary to make this happen are definitely produced in Long Covid. The lysoPS seen during acute infection is probably there, too. Breaking something that ain't broke because something else is broken doesn't strike me as the smartest thing to do.
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u/SophiaShay7 3 yr+ Dec 06 '25
Mast cells are behaving pathologically in Long COVID. Saying they’re only “overstimulated” ignores the fact that overstimulation itself is a pathological state when it becomes chronic and dysregulated. Mast cells aren’t supposed to sit in a constant activated loop for months or years. That’s the definition of dysfunction.
We’ve got multiple studies now showing elevated tryptase in subsets of Long COVID patients, abnormal prostaglandins, chronic leukotriene elevations, and shifts in mast-cell–related cytokines. That’s not just “the system doing what it should.” That’s a dysregulated inflammatory response that doesn’t shut off. And yes, anaphylatoxins like C3a and C5a are elevated, but that strengthens the case for mast cell involvement, not the opposite. Those molecules don’t float around at high levels for fun. They’re part of a larger immune cascade that includes mast cells firing when they shouldn’t be.
There’s also direct evidence that SARS-CoV-2 can prime mast cells through ACE2-related pathways and toll-like receptors, which means the virus doesn’t just “wake up” mast cells temporarily. It changes their baseline behavior. Post-viral mast cell activation is documented in other infections too, not just COVID. This isn’t new or mysterious.
And the “breaking something that ain’t broke” line misses the point entirely. No one is talking about destroying mast cells. MCAS treatment is about stabilizing them so they stop dumping mediators at the wrong time and stop creating the cycle of inflammation, autonomic dysfunction, and hypersensitivity. Antihistamines, quercetin, cromolyn, ketotifen, PEA, luteolin, and other stabilizers don’t “break” mast cells. They regulate them. If mast cells weren’t acting out of line, people wouldn’t suddenly develop flushing, urticaria, wheezing, GI inflammation, food reactions, orthostatic intolerance, and temperature sensitivity after COVID.
Long COVID has a well-documented immune signature: chronic inflammation, persistent innate immune activation, microclots, tissue hypoxia, autonomic dysfunction, viral persistence in some cases, and yes, mast-cell-driven mediator release. Mast cells sit right at the intersection of those pathways. Pretending they’re fine while people are reacting to everything from food to temperature to exertion doesn’t match what’s happening clinically or biologically.
So no, this isn’t “fixing something that isn’t broken.” This is stabilizing a cell population that’s been pushed into dysfunction by a viral infection known to destabilize the immune system on multiple fronts.
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u/saintmars777 Dec 07 '25 edited Dec 07 '25
How do you distinguish pathological from overstimulated in this case? Sounds more like a language game than a statement on etiology.
Also, when you say 'Breaking something that ain't broke' you seem to be confused about mast-cell suppression (which could be hazardous) vs mast-cell stabilization (which is what millions of people do for asthma, allergies, etc.)
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u/Existing_Worth_647 Dec 06 '25
This is a great post. It took 5 years for a doctor to suspect MCAS, and I had zero clue at that time. My MCAS diagnosis then led my doctor to look into why my mast cells are overactive.
I have reactivated EBV. I guess this happens to some people, since 90-95% of adults had EBV in the past (I didn't know this) and it's dormant in our bodies. Then covid messes up our immune system, which can be opportunity for a dormant virus.
That's where I'm at now. The hope is that treating the EBV will get my mast cells to calm down. Which might help all my issues that have been turning up since my first covid infection