How to get out of a reaction cycle

If you have mast cell disease, your basic arsenal for managing your disease should include elimination of/ avoidance of known triggers, low histamine diet, second generation H1 antihistamines and H2 antihistamines.  Leukotriene inhibitors, aspirin, mast cell stabilizers, steroids and anti-IgE are also possibilities for maintaining a baseline.
As a mast cell patient, a decent baseline is what you are going for.  A reasonable baseline does not always mean that you can live the same way you did before your diagnosis.  It means that you are somewhat functional on a day to day basis.  What this looks for is different for everyone, but I aim for not being in bed for 20 hours a day, not being in 5/10 pain every day, being mentally coherent.  Most importantly, you should not have to take rescue meds frequently.  If you need rescue meds often, then you are not covering your mast cells well enough with your regular meds.  If you have eliminated triggers, then this usually involves tweaking your meds. 
I’m going to give you my insights on what that looks like, but please keep in mind that any med changes should be discussed with your treating physician.  We are all different people and med dosing can be affected by many factors. 
Part of why mast cell patients are prescribed second generation H1 antihistamines is because they are usually not sedating, have little anticholinergic activity and are, to be honest, pretty safe.  Mast cell patients often take several times the recommended daily dose on medications like loratadine and cetirizine.  (Please note: the daily recommended dose for Benadryl, which is a first generation H1, should be respected – overdosing can have serious consequences.)  So while the average person may take one Zyrtec a day for allergies, a mast cell patient may take 3 or 4 a day.  The same is true for the H2 antihistamines, like ranitidine and famotidine.  It’s not unusual to dose very high on those. 
If you have uncontrolled symptoms on second generation H1 and H2, changing the meds to something else in the same class may help.  Sometimes Pepcid works better than Zantac, or whatever.  Some people find that using one Allegra and one Zyrtec works better than two Allegras.  Consider also that inactive ingredients can be triggering and thus decreasing the effectiveness of a med.
If you have screwed around with H1 and H2 meds and have increased doses, adding leukotriene inhibitors, cromolyn or atypical H1 meds, like promethazine or doxepin, may help.  If that fails, ketotifen helps a lot of people, and anti-IgE (Xolair) has benefited some mast cell patients.  Beyond this, you are looking at things like regular IV fluids, steroids, and less palatable choices.
As I mentioned before, having a good baseline means not using rescue meds regularly.  This is really important to feeling as well as possible.  Serious reactions take a while to recover from, even if they don’t need epi.  So if you’re having one every day, it is impossible to get to your baseline without serious intervention.  The meds used to control serious reactions, including Benadryl, can cause rebound reactions that look like anaphylaxis, but are not anaphylaxis.  Let’s talk about this.
Benadryl can cause rebound reactions for two primary reasons.  The first is because it is a very strong antihistamine and it stops histamine release symptoms really well.  One of the things Benadryl does is it stops mast cells from releasing histamine.  So when it wears off, mast cells tend to release a lot of that histamine at once.  Another release is that Benadryl has very strong anticholinergic action.  When your dose wears off, you can have what’s called “cholinergic rebound.”  This can cause headache, nausea, vomiting, diarrhea, brain fog and other symptoms.  Sound familiar?  This is why people feel “hung over” when their Benadryl wears off.  Second generation H1 antihistamines, like cetirizine and fexofenadine, have almost no appreciable anticholinergic activity so they tend to not have this side effect.
Mast cell patients get hit with the double whammy of sizeable histamine release at the same time as they get hit with cholinergic rebound.  So rebound reactions can feel like anaphylaxis, but they’re not the same thing.  If you take Benadryl every day, you are going to have a rebound reaction every day.  It may not be severe, but this is not uncommonly the culprit in patients who say they always get sick around the same time every day. 
Another reason why it is generally not recommended for mast cell patients to take Benadryl every day is because it can stop working.  This is called tachyphylaxis and it basically means your body gets used to it.  When you need to use epinephrine, you are counting on Benadryl and steroids to help control the effects of anaphylaxis on your body.  Patients in whom Benadryl is ineffective get into very dangerous situations when they anaphylax.  I have a few friends like this and it is seriously not pretty. 
It is possible for anaphylaxis to be biphasic or protracted.  Biphasic reactions are not common, but seem to be more common in mast cell patients than the general population.  (This is my personal observation.)  In these reactions, once the reaction is stopped with epi, you can have another anaphylactic episode of the same or worse intensity without a trigger.  This generally happens within 24 hours and is the original reason Epipens were sold in pairs.  In protracted (sometimes called multiphasic) reactions, this can continue to happen for a number of days.  I find in my personal experience that use of epi early is the best way to avoid multiphasic reactions. 
If you absolutely must take a medication that causes a serious reaction (by which I mean not a typical side effect), desensitization is usually recommended for mast cell patients as opposed to taking antihistamines with each dose.  This method really just suppresses the immediate symptoms, not the inflammatory response.  Drug reactions for mast cell patients can be serious and any reaction can escalate even when it has been mild in the past.  For patients who react to salicylates, but need to take aspirin, Dr. Castells has written an aspirin desensitization protocol that is frequently used.
Part of why people get into these cycles with rescue meds is that they often don’t understand why they are having reactions.  Mast cell patients need to keep careful inventory of their daily histamine level because things that may not cause reactions individually can cause a reaction when you have them all together.  For example, if you have a relaxing day with no stress, maybe you can eat a spinach salad.  But if you go for a walk outside in the heat, and you eat that same spinach salad, you may have a reaction.  This doesn’t just happen to mast cell patients – there are plenty of recorded instances of patients having allergic reactions to food ONLY IF THEY EXERCISED THAT SAME DAY.  This is because exercise increases histamine.  Heat increases histamine.  Eating increases histamine. Stress increases histamine.  Sex increases histamine.  So all of this histamine adds up.  So you may be able to drink a beer, or you may be able to walk two miles, but if you try to do both the same day, you may have a reaction. 
Of course, there is also an idiopathic aspect to mast cell reactions, which means that some people have symptoms for truly unexplained reasons.  However, I find these happen a whole lot less when you really track activities/histamine and try to eliminate triggers. 
Part of how I evaluate my “histamine baseline” for any particular day is by certain physical parameters that I refer to as my “mast cell dead giveaways.”  If these are present, I know I am already starting out as reactive and need to lay low and avoid histamine that day.  Allergic shiners, which look like black eyes, or dark circles under the eyes, are one for me.  Swelling in my fingers tells me I’m having some edema from mast cell degranulation.  The taste of metal in my mouth often precedes reactions.  Skin being more reactive than usual is a very clear indicator for me.  On a reactive day, squeezing my arm with my hand will make my entire arm turn red.  I take my blood pressure in the morning and if my whole arm is red or has hives when I take off the cuff, it is a clear sign to me to not take risks that day.  Any type of “cold symptoms” (cough, stuffiness, clearing of the throat, sore throat) and I have to assume infection, which contributes to mast cell activation and thus to your histamine quota. 
I have written before about how to manage mast cell reactions with medication, so please refer to that post for more details.
Keep track of your histamine inventory.  Learn the “dead giveaways” for your body so you can self check.  If you’re taking Benadryl every day for symptoms, it can often be resolved with increasing meds/ adding other meds.  Taking Benadryl every day should be avoided, especially because it causes rebound reactions that can mimic anaphylaxis symptoms. 

12 Responses

  1. BluenotesBb October 19, 2014 / 7:12 am

    I have just started my journey in the diagnoses of a mast cell disorder, and I can not tell you how helpful your blog and knowledge has been to me. This is one hell of a journey, thank you for writing this as it explains a lot with what I have been going through.

  2. Carole Reed October 10, 2015 / 10:38 am

    Hi Lisa,
    Am recently diagnosed by Dr. Afrin with MCAS and borderline Polycythemia Vera. He recommended Imatinib but it is very expensive and being that I am on Medicare, retirement income and in the proverbial doughnut hole right now, I can not afford $1000 every 31 days. Such is life, right?
    I love your blog and am a member of your group on Facebook. Just wanted to stop by and say thank you for all that you do! You certainly make it easier to navigate through this disease.
    Carole Reed

  3. Kathy October 12, 2015 / 9:39 am

    Oh, my thank you for the post! I used Benadryl pretty much every day for like 15 years to control severe allergies and anxiety. I just quit cold turkey about a week ago. I can’t believe how much better I feel. I thought my anxiety would get worse, but just the opposite has happened. From your explanation of the rebound effect, and the symptoms I experienced while on chronic Benadryl, I think this is exactly what was happening. I’ve been googling like crazy trying to find some support for a rebound effect, and so glad I found this post.

  4. Angela spranget December 18, 2015 / 10:08 pm

    Please help me with info and how to get started. I was just diagnosed. Have been very sick thought with allergy-cold. Now this mast cell thing. I am terrified and have hives all over. Taking tons of antihistamine products but got more hives!!!..really feel like I’m going to fall apart..have been crying all day. I need some help. Thank you!

    • Lisa Klimas December 18, 2015 / 11:36 pm

      There are lots of guidance posts on the blog for symptoms, diagnosis, and treatment. The Fact Sheet is a good place to start.

  5. Angela spranger December 18, 2015 / 10:11 pm

    Has this ever been linked to a tick bite also I meant to ask?

  6. Angela spranger December 18, 2015 / 10:11 pm

    Has this ever been linked to Lyme disease?

    • Lisa Klimas January 5, 2016 / 9:41 am

      Some people who have Lyme also have MCAS, and some people were misdiagnosed with Lyme when they really had MCAS. They appear similar in many ways.

  7. Jerry April 12, 2016 / 3:44 pm

    Been trying to find out why my mcas symptoms are worse at night. After reading the article it seems its because histamine builds up in the day?
    This is very valuable info since I might eat something thst doesn’t initially cause symptoms but will add to histamine level.

  8. Loren May 19, 2016 / 8:08 am

    Excellent write up!

  9. Carolyn July 9, 2016 / 9:44 pm

    My daughter, 6, has suddenly become reactive to the rain – even a light summer drizzle, snow, water from the hose or splash pad. She developed atopic dermatitis (eczema)/which started as two little spots, one on the same spot of each upper, outer arm when she was a baby and became quite widespread. We found ointments like Betaderm just seemed to “push” the eczema rashes to another spot and it settled in her hands so we avoided it and modified her diet to help manage it. Later she had a terribly reaction to peanut butter with more than half her body covered in so many hives they just became raised bands. By the time she was 3, her hands would swell and split open and weep, especially in the humidity. We were told by so many dermatologists to just keeps using steroid creams and Benadryl every night but I found she rebounded to the Benadryl too. More diet modifications, salt water soaks, and the use of topical cortisone sparingly helped control it. Then came the dreaded asthma, tried as we may have to avoid it. At first it was if she ran around a lot or if it was humid, then one day she got a cold and we were advised to use steroid inhalers pro actively every time she got sick, then all winter because of cold season, then all summer because of pollens. But again, because we noticed a bit of rebound, we continued to use only a 10 day course when she got sick and tapered off slowly (to which we were told was unnecessary since “she is on the lowest possible dose”). But then we found she’d be on 10 days and then off for a week and then back on again for another 10 days so we recently succumbed to 4 consecutive weeks believing it was necessary and “harmless.” And, we got her asthma under control so she could run and jump around without an issue, which was so great for her…except now that she’s been off of it for a week she is having massive body-wide breakouts and has had a few doses of Benadryl now to control it.

    I thank you for this article – I think it offers more insight than the doctors have given me and confirms my suspicions about rebounding. I will choose second generation antihistamines in the future and I am going to put my daughter on a low histamine diet and watch for triggers as you described and restrict her activities each day accordingly. I know the goal for children is to not miss out on play but now we are at the point the we are terrified to take her swimming or out on the lake or even forget her umbrella if it rains. 🙁 I hope she can overcome this. It must be awful for her to feel itchy so often and our whole family lives in fear of anaphylaxis for her.

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