1) You're in good company. MCAD, and in particular MCAS, went from being painfully underdiagnosed in its infancy and adolescence to the medical equivalent of the zombie apocalypse with Covid-19 and a number of other factors. Now, too many of your patients have been bitten for comfort. (Thanks for joining the resistance.)
2) Mast cells are distributed throughout the body. Symptoms can be anywhere, and patients present very differently, even within nuclear families. Multiple seemingly unconnected and unexplained symptoms in different bodily systems is the hallmark for inappropriate mast cell activation and run the gamut in severity.
3) There is no test to rule out MCAS (mast cells behaving badly). Tryptase may help point towards SM (proliferation of mast cells) or Hereditary Alpha Tryptasemia but may be challenging to catch at baseline and is in no way indicative of disease severity (as many, particularly, with MCAS with tryptase of 2, for example, have more severe cases than others with tryptase in the 300's for whom the disease has very little impact on daily life). The overwhelming majority of cases (see prevalence), including "severe" cases, are MCAS.
4) Mast cell triggers are not allergens. They can change, even day to day, based on "bucket" and other considerations, and cannot be tested. Skin testing for allergens is contraindicated if a mast cell disorder is suspected due to serious and long term risks, and are also extremely inaccurate at identifying allergens in this population. Blood tests are recommended (see this page) for differential diagnosis.
5) Histamine is only one of hundreds of mast cell mediators, and histamine intolerance is an unrelated but often conflated condition which involves neither inappropriate mast cell mediator release (MCAS) nor mast cell proliferation (SM). Luckily, H1 and H2 are critical pathways which in the patient with MCAD allow degranulation to cause body-wide and long-term events, and blocking these sufficiently (which tends to require a number of trials of different H1 and H2 antagonists multiple times throughout the day, as there is no way to predict which will work best for a particular patient, or even which will work at all for a particular patient) can help prevent long term damage to the body that would otherwise occur. After baseline treatment is established, other classes are frequently also important in the management of these cases.
6) As you might expect, mediator testing or other laboratory confirmation for MCAS is, at best, challenging. We can test a few, but even when handled in very specific ways, these frequently produce false negative results because mediators themselves degrade so quickly. We're trying to catch the fleet-footed messenger rather than the army. When patients meet the symptomatic criteria and other possible causes for these symptoms have been responsibly investigated, symptomatic improvement from treatment is most often necessary to confirm this diagnosis.
7) SM is much more straightforward to diagnose but remains quite rare. All forms of SM offer treatment options, but roughly 90%, and likely more, are classed as Indolent Systemic Mastocytosis, which sometimes presents asymptomatically.
8) In the United States and many other countries, baseline treatment for any symptomatic, systemic mast cell disorder is available over the counter, but many patients require their medications to be compounded due to excipient triggers. Think olive oil, rice flour, dextrose, sucrose...
9) Triggers for the disorder to "appear" (and "appear" is most typically what it does, particularly in the case of MCAS) can be anything from Covid-19 to pregnancy, various infections, surgical or other procedures, radiology, and so on. In general, for most patients, mast cell triggers may encompass a unique a gamut of seeming oddities, from pressure changes to electromagnetic fields to chemicals and foods. While dietary and a variety of lifestyle changes are in most cases necessary, these are highly individual, with some notable exceptions, and are typically insufficient to address symptoms and damage on their own.
10) The most recent estimates regarding prevalence of these disorders are as follows: MCAS: 1 in 5 or 6 (17% of population). All forms of systemic mastocytosis: 1 in 10,000. Aggressive systemic mastocytosis: 1-2 in a million/year.