I don't know if histamine is elevated in every case of MCAD, but several mutations have been found affecting mast cell regulation and mediator expression, and mast cells can selectively release mediators without degranulation, so in theory I think there could be MCAD cases without elevated histamine.

But if you're asking if histamine always shows up elevated on tests in people with MCAD then no, and it's not required for diagnosis of MCAD. They test for elevation of several other mast cell mediators or their metabolites such as tryptase, chromogranin A, prostaglandin and leukotrienes.

Often it can be difficult to detect elevated mast cell activation in MCAD. If the samples are not taken during or soon after a substantial flare of symptoms, when the mast cells would be releasing the mediators, then they often come back normal on tests. There can also be sample handling issues where they were not kept chilled at all times so they can break down and give false negatives.

But criteria for MCAS, which relies most on these MCA tests, is still tentative and not yet validated to ensure it always catches every case of MCAD and only cases of MCAD. Some patients are treated for suspected MCAS which couldn't be confirmed with tests to fit the proposed criteria.