Other Common Comorbidities

(a VERY incomplete list)

Gastroparesis, delayed motility, and malabsorption

I challenge you to find a trifecta patient who has not experienced at least some degree of gastroparesis or delayed motility. You probably know the feeling: you experience nausea or bloating or feel too “full” after eating a normal or even quite small amount of food. If you’re especially unlucky, you might spew last night’s pasta, still largely intact, all over the living room and mistake it for worms. Mast cells are found throughout the digestive tract. Food (even if it didn't start out as a trigger) which sits in the stomach in particular tends to cause inappropriate mast cell degranulation there, and mast cell reactions anywhere seem to lock down the stomach for many patients. Putting foods in blenders and eating only soft things (no stringy fiber, difficult to digest meats, large quantities of fats or oils, or leafy greens unless pulverized), taking smaller meals over more time, slow movement after eating (like walking), and heat are common symptom helps. Some also require ondansetron (zofran) or other meds in addition to their mast cell treatment.

Bleeding issues

Mast cells misbehaving can cause either clotting or bleeding, especially locally...and you don’t always know which you’re going to get. Mast cells frequently release inappropriate levels of heparin, for example, which can cause (in addition to EDS factors which slow wound healing and frequently comorbid bleeding disorders) excessive blood loss in unexpected settings. It’s important that precautions be taken and surgical teams briefed and prepared for either the possibility of blood loss or unexpected clotting before any procedure.

Weight changes or thyroid issues

“I am overweight,” “I am underweight,” and “I just went from one to the other, this morning.” are among the most baffling complaints of some mast cell patients. Even more frustrating are the number of these patients who have had their symptoms ignored or been told by the doofus variety of physician that they “just need to lose weight” (Swelling during reactions leads many undernourished individuals to appear overweight, and this mistaken assumption is common even in hospitals in acute reactions which cause more or less all-over swelling) or, in the case of “underweight” patients, that they must have an eating disorder, followed by, instead of an evaluation of the complex dietary considerations of the individual patient, calls for “more nutrition!” like “more cowbell!”

There are also a number of trifecta patients with diagnosed thyroid conditions, and unintentional pharmacological overcorrections of these conditions are common (of course, as almost all of these patients know from experience, so are missed diagnoses).

A particular caution about low dose naltrexone: LDN has a tendency to normalize thyroid function over time, which is wonderful, but this doesn’t always happen when you expect. If you’re taking T3/T4 and are on LDN, for example, keep an eye out for symptoms of hyperthyroid (heart palpitations, anxiety, mood swings, increased sensitivity to heat, hair loss, menstrual changes, and so on) and have your levels checked regularly with any thyroid condition, since at some point, you are likely to need to cut back or even eliminate your thyroid medication. LDN also has a tendency to take down swelling too quickly for comfort, causing many seemingly “overweight” patients to lose “weight” much too quickly than can be attributed to thyroid correction. In this case, even if you are lopsided, and especially if you are feeling well and even beginning to see some symptom improvement, try not to let well-meaning support groups talk you into the most daunting of cancers for which sudden weight loss is also a symptom.

Dental issues

Most mast cell or EDS patients have special dental considerations, and dental issues of many different kinds are common with either disorder irrespective of patients' vigilance with oral care. Finding a dentist who will address the complexity of these cases and other individual needs, such as premedication and a variety of precautions for even simple procedures like cleanings, is very important. Many patients dump several dentists, and that’s okay; many dentists need to be dumped.

Brain fog and other neurological challenges

There are a number of reasons trifecta patients might have difficulty concentrating, difficulty remembering things, and general fatigue or a “blurred” feeling of the world. These complaints are very common and, while everyone should be screened appropriately for any number of other conditions which can also cause these problems, feeling like you’ve been “out of it” is not a good reason to assume the worst.

“Masty rage” and other unexpected emotional experiences are also very common, particularly during reactions. They run the gamut from uncontrolled sobbing while contemplating the beauty of your mousepad to seemingly unprovoked screaming in tongues while hurling teapots. Don’t blame yourself. You were drugged (by your body, in an attempt to fight a reaction, and you just fought the teapot instead.)

Osteoporosis or Osteopenia (as well as arthritis, and of course teeth and jaw issues)

Both EDS and MCAD have startlingly high populations who suffer from premature bone loss, and of course EDS is often to blame for unexpected cases of arthritis, even in very young people. Treating mast cell mediators to help prevent further loss, finding safe ways to exercise, and in some cases supplementation are important. K2 and D3 seem to be the most recommended. Since mast cell degranulation can wreck havoc with calcium channels (and also for a lot of other, non-zebra reasons), you may want to be wary of calcium supplementation.


General pain. Bone pain. Pulled-something-wrong-that-you-can’t-see pain. Neuropathic pain. Want-to-throw-a-teapot-because-your-physican-says-nothing-is-wrong-with-you-and-you-can’t-be-in-pain pain. They’re all common. So is an unexpectedly high pain tolerance that confuses emergency room physicians when these patients get into “normal” scrapes.

In most cases, pain management is not a one-step program. Talk with your medical care team. Always seek appropriate treatment for your contributing conditions. Consider a variety of creative body supports, lifestyle changes, creams, alternative therapies...you get the idea. Things like LDN and infrared and PEMF seem to be helpful to many, as is biofeedback in some cases. Don’t give up because the three things you’ve tried weren’t the answer; the answer may well be six other things.

Organ issues

Mast cells and faulty connective tissue are a recipe for a number of organ issues. Urinary issues, including IC, are especially common, and mast cell treatment is frequently especially important for these cases. Especially with EDS, prolapses are also very common and can happen anywhere. The most common are prolapsed uterus and bladder (especially in women who have carried pregnancies), colon issues (same), and chiari malformation (brain stem “sagging”). Many also have vertigo, tinnitus, and blurred vision, all of which are commonly at least made worse during mast cell reactions. A sometimes happy accident: Ketotifen is available as an eye drop in the US, so some patients who are not familiar with MCAD inadvertently but successfully treat their eye symptoms with this before discovering their MCAD.


Especially when symptomatic in the esophagus, you can chicken-and-egg this one all day (and it might depend on the day of the biopsy, if you had one, and what you were reacting to at the time, to get a diagnosis, which might not have been necessary, because...). Your EOE symptoms might be indistinguishable from your MCAD symptoms. Strictures requiring esophageal dilation are also somewhat common in EDS and mast cell populations. About two thirds of patients with EOE don’t respond to PPI’s (Of course, as though by magic, many subsequently do respond to H2 antagonists, taken regularly in combination with H1 antagonists, like...mast cell treatment. Cool, huh?), and the American Gastroenterological Association recommends diet therapy (eliminating triggers), soft foods, and topical steroids.

Autism Spectrum

Chicken and egging this one can only lead to a geneticist civil war (No one wants this.), so just know that an astonishingly high percentage of "trifecta" patients fall somewhere on the "spectrum," and symptom improvement (of the unwanted kind of ASD "symptoms") by identifying triggers and treating previously undiagnosed mast cell disorders is common. The trifecta population tends to be very bright, very adaptable, and very competent, which is most definitely for the best, but they are also, like many patients previously identified as having "Asperger's,", very good at camouflaging their symptoms, which sometimes makes it less likely that practitioners will recognize an underlying mast cell disorder (or, unfortunately, much of anything else).

Any number of non-zebra conditions that just don’t present “normally.”

Add “atypical” to it, and you may well be dealing with a mast cell complication.

In some cases, asthma and GERD do present fairly typically, so these are more often “caught.” However, many patients discover that any number of other conditions, often with odd presentations, are caused by mast cell dysfunction. In some cases, these conditions mysteriously resolve themselves after beginning adequate mast cell treatment. So if you’re on the 50-not-quite-right diagnosis route, don’t panic.