Treatment options: Less common medications for mast cell disease

One of the most common complaints by mast cell patients is that therapy is symptomatic, not curative.  While there is currently no cure for mast cell disease, there are some less common options that some people might be unaware of.  I’m going to those today.

Part of why treating people with systemic mast cell disease is so difficult is because symptom profiles and disease progression is very individual.  The most effective first-line treatment is trigger avoidance.  For some people, this can be frustrating as not everyone knows their triggers, and finding them through trial and error can be dangerous and intimidating.  However, it still remains important in preventing anaphylaxis, to the extent that it is possible.

Treatment with medication is very specific to the patient.  This typically involves H1 and H2 antihistamines (loratadine, ranitidine, diphenhydramine, etc) and mast cell stabilizers (cromolyn, ketotifen).  Some patients also receive leukotriene inhibitors (Singulair, Zyflo.)  Finding the correct combination can be a slow process as some medications take up to four weeks to show reduction in symptoms, and addition of multiple medications at once is discouraged due to high reactivity of mast cell patients.

Many patients are frustrated by lack of symptom control with these medications.  For patients resistant to these therapies, there are other, less common options.  These drugs can reduce mast cell activity (though not mast cell quantity.)  These include prednisone, cyclosporin, methotrexate (low dose), and azathioprine. 

Prednisone is a corticosteroid that suppresses the immune system.  It is used to treat autoimmune diseases and cancer, but makes the patient more likely to contract infections.  It has many side effects, and long term use should be avoided if possible.

Methotrexate is used to treat cancer and autoimmune dieases.  It inhibits the metabolism of folic acid.  Cells need folic acid to make new DNA and therefore new cells.  Methotrexate is usually well tolerated compared to other options.

Cyclosporin is typically used to prevent organ rejection after transplant due to its immunosuppressant activity.  It works by preventing growth and activity of T cells, a type of white blood cell.  It is also used for autoimmune disease, rheumatoid arthritis and chronic urticaria.  It also has a substantial side effect profile. 

Azathioprine is used to prevent organ rejection after transplant and also autoimmune diseases.  It works by interfering with DNA synthesis.  This means its action most strongly affects cells that proliferate (make new cells quickly), like T cells and B cells, as well as other cells of the immune system.  Its main serious side effect is bone marrow suppression, as bone marrow cells are proliferative.

Another drug to be considered for resistant mast cell disease is Xolair, a medication that interferes with IgE, a molecule that causes mast cells to break open.  Tyrosine kinase inhibitors, including Gleevec and Tasigna, have also been used in severe cases, including those associated with frequent anaphylaxis.   In some case reports, these medications have all been very effective at providing symptom relief; however, they, like other medications mentioned in this post, have the potential for serious side effects.

Medications mentioned in literature as possibly being effective include everolimus, sirolimus, and temsirolimus.  However, in the single trial that tested everolimus on mast cell patients, no significant activity was noted.

As always, side effects should be considered against the possible benefits of medications.