In the summer of 2012, I was asked if I had ever read anything about mast cells and Gadolinium or NSF. I vaguely remembered mast cells being mentioned in one study, but it obviously didn’t strike me as being important or I would have done some research on it then. But after digging around a bit, I came away thinking that there might be a connection between mast cells and the disease progression of NSF/GASF.
For those who don’t know, mast cells are found in tissues throughout the body, particularly in association with structures such as blood vessels, peripheral nerves, in mucosal membranes, skin and subcutaneous tissue. Mast cells are bone marrow-derived and particularly dependent upon stem cell factor for their survival. They express a variety of phenotypic features within tissues that are determined by their local environment. Mast cells appear to be highly engineered cells with multiple critical biological functions. They may be activated by a number of stimuli. Activation through various receptors leads to distinct signaling pathways. Multiple secretory granules contained within the cytoplasm of mast cells have unique histochemical properties and are a characteristic structural element of those cells. Mast cell granules store multiple mediators, which are responsible for various functions of mastocytes in both physiological and pathological processes. Allergen-induced mast cell degranulation is the basis of anaphylactic reactions. Mast cell activation may also be followed by the synthesis of chemokines and cytokines. Cytokine and chemokine secretion, which occurs hours later, may contribute to chronic inflammation. Many more details can be found in the 47-page PDF of the 1997 article, Mast Cells, by Metcalfe, Baram, and Mekori.
What I found even more interesting from my research was that there is something called “Mast Cell Activation Syndrome” or MCAS. In 2010, Akin et al published Mast Cell Activation Syndrome: Proposed diagnostic criteria. When I read over the list of symptoms suggested to occur in MCAS, I thought I would fall out of my chair because I could check off so many of them. It seems that when patients have a wide-range of unexplained symptoms and extensive medical evaluations without a definitive diagnosis occur, the diagnosis of MCAS is often applied. The authors commented that “the last several years have witnessed an increasing use of the term mast cell activation syndrome (MCAS) as a diagnosis for subjects who present with signs and symptoms from flushing to hives, abdominal pain to diarrhea, and paresthesia to cognitive dysfunction”.
Now, I am not saying that we all need to run out and try to get a mast cell diagnosis. No, instead I am beginning to wonder if the reason that the term “Mast Cell Activation Syndrome” is being used more often as a diagnosis is because more and more people who have symptoms of Gadolinium Toxicity end up with that diagnosis when nothing else can be found. I think that is a very real possibility given the fact that so few doctors and patients even know about the risks associated with Gadolinium-Based Contrast Agents. That is especially true for the non-renally impaired patient population since most doctors are working under the belief that patients with normal kidney function do not retain Gadolinium from their contrast-enhanced MRIs and MRAs.
That might sound far-fetched, but I actually found a 2009 editorial written by Dr. Whitney High in which he talks about mast cells and how they might be involved in NSF. Dr. High said, “In fact, I predict that a greater appreciation of a role for mast cells in NSF, and perhaps other fibrotic and sclerotic diseases, will evolve over the ensuing years”. The article is: Estimates of Risk, Empirical Treatment Observations, and Unexpected Laboratory Findings Reveal the Complexity of Nephrogenic Systemic Fibrosis (Note that the full-article is not freely available to the public.)
In their 2012 study, Influence of MRI contrast media on histamine release from mast cells, Kun and Jakubowski demonstrated that both ionic and non-ionic GBCA are able to induce mast cell degranulation in vitro. Their results “proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration”. They noted that degranulation of mast cells may cause multiple symptoms and complications related to the mechanisms of immediate and delayed hypersensitivity.
It appears that there may be a connection between mast cells and Gadolinium. Mast cells might not explain why we retain Gadolinium, but it seems that they may play a part in the development of at least some of the chronic symptoms of Gadolinium Toxicity.