Mast Cell Activation Syndrome: What do allergies, infections, and low platelets have to do with anxiety, depression, ADHD, and autism?

Mast Cell Activation Syndrome:  What do allergies, infections, and low platelets have to do with anxiety, depression, ADHD, and autism?

Have you ever wondered if your hay fever is connected to your low mood, or if your IBS is connected to your anxiety? How about your gluten intolerance or food sensitivities? Are they connected to your depression, fatigue, headaches? The short answer is yes. The long answer is the subject of this blog.

Mast cells are an important part of the immune system, so important that no one has ever been found with very low or non-existent mast cells. Mast cells reside in our tissues, especially those that are near the outside world such as the skin, lungs, digestive tract, mouth, conjunctiva, and nose. They are there to protect us from invaders. However, mast cells can also be found in the uterus, bladder, and other organs.

Mast cells become activated by “assaults,” such as particular foods, alcohol, opioids, infections, and certain antibiotics. Upon assault, mast cells release several molecules such as histamine and cytokines into the extracellular red_wine5environment. In other words, mast cells provide an inflammatory reaction in an effort to remove the offender.

When histamines are released, we experience runny nose, watering eyes, sneezes, headaches, stomach pains, nausea, and fatigue. In most cases, these symptoms go away when the offending substance has been removed (e.g. no pollen in the winter months usually means no “hay fever”). However, in the case of Mastocytosis, there are too many mast cells. This can lead to a hyper release of histamines and cytokines causing severe inflammation and sometimes anaphylactic shock.

While full-fledged Mastocytosis is rare, there is another disorder that occurs on the continuum of mast cell disorders. It is most often known as Mast Cell Activation Syndrome (MCAS), but is also known as histamine intolerance and histamine sensitivity. In the case of MCAS, there are usually a normal number of mast cells, but the level of histamine release is elevated. Also with MCAS, an individual may have the symptoms and genetic markers of Mastocytosis. Therefore, MCAS is most likely a “lighter” version on the Mastocytosis continuum.


So, what are the symptoms of MCAS?

The following information is taken from the work of Lawrence B. Afrin, M.D., Medical University of South Carolina. Dr. Afrin is one of the world’s leading experts on Mast Cell Activation Syndrome.

According to Dr. Afrin (2013), MCAS often begins in childhood or adolescence with vague symptoms. Individuals may be plagued for decades by mysterious symptoms, going from one doctor to another looking for answers. MCAS can affect every system in the body and multiple systems at one time. Therefore, it can be very difficult to diagnose.

Below are common symptoms of MCAS categorized by body system. Keep in mind that people with MCAS don’t usually have all these symptoms, but they often have many of the symptoms, and they often have symptoms involving more than one body system. Folks usually don’t think that stretch marks, weepy eyes, tinnitus, and rapid heartbeat could be caused by the same thing!

Constitutional

  • Fatigue/malaise is the most common complaintTired Woman 3
  • Diaphoresis (“night sweats”)
  • Weight gain that often begins slowly, but then progresses at a rapid pace (without any diet or exercise changes)
  • Pruritis (itching)
  • Sensitivities to various medications, foods, and environmental provocations
  • Strong reactions to venoms (e.g. bee stings, mosquito bites), heat, cold, and UV light

Integumentary (Skin, Hair, Nails)

  • Rashes
  • Warts
  • Pruritis
  • Slow wound healing
  • Alopecia (loss of hair)
  • Striae about the trunk (bands, stripes, lines that look like stretch marks)

Opthalmologic (Eyes)

  • Irritated, dry, gritty, itchy, “always watering” eyes
  • Trouble focusing eyes that lasts minutes to hours

Otologic (Ears)Ear infection

  • Non-infectious inflammation
  • Otitis media (middle ear infection)
  • Hyperacusis (sensitivity to sound) or hypoacusis (reduced sensitivity to sound)
  • Tinnitus (ringing in ears)

Sinonasal

  • Sinus and nasal congestion
  • Olfactory intolerances (sensitivity to smells)

Oral (Mouth)

  • Burning mouth syndrome
  • Swelling of tongue, lips, mouth

Pharyngeal (Throat)

  • Throat hurts (comes and goes)
  • “Tickle” in the throat
  • Chronic post-nasal drip

Lymphatic

  • Pain in the left upper quadrant (left upper abdomen)
  • Tender lymph nodes

Pulmonary (Lungs)Woman-Feeling-Shortness-of-Breath-an-Chest-Pain

  • Unprovoked, subtle shortness of breath (dyspnea), sometimes with wheezing
  • Idiopathic chronic cough (mostly non-productive)

Cardiovascular

  • Heart palpitations
  • Tachycardia (rapid heartbeat)
  • Sudden onset weakness, dizziness
  • Chest pain or discomfort

GI Tract

  • Inflammation
  • Gastritis
  • Nausea
  • Abdominal pain
  • Diarrhea

GU TractInterstitial Cystitis Awareness

  • Painful interstitial cystitis (often mistakenly diagnosed and treated as a urinary tract infection)
  • Dysuria (pain on urination)
  • Vulvar vestibulitis (pain around the opening to the vagina)
  • Vaginitis (vaginal inflammation)
  • Low back pain
  • Lower abdominal pain

Musculoskeletal System

  • Fatigue and weakness
  • Fibromyalgia
  • Hypermobility
  • Pain that doesn’t respond to traditional pain medication

Neuropsychiatric

  • Headaches
  • Dizziness, weakness
  • Tingling, numbnessInsomnia
  • Low-normal to slightly low B12 levels
  • Insomnia, difficulty falling asleep, difficulty staying asleep
  • Obstructive sleep apnea
  • Irritability
  • Depression
  • Anxiety
  • Panic
  • “Brain fog” (e.g. decreased short-term memory, trouble with word finding)

Endocrine/Metabolicinsulin resistance

  • Vitamin D deficiency
  • Hypothyroidism
  • Elevated iron (ferritin) – but variable from test to test
  • Ovarian dysfunction (e.g. PCOS)
  • Metabolic syndrome (insulin resistance)

Hematologic

  • Low platelets, thrombocytopenia
  • Anemia
  • Easy bruising

Immunologic

  • Increased risk of hematologic malignancy, particularly myeloid (e.g. acute myeloid leukemia, acute promyelocytic leukemia)
  • Slow wound healing


Are there other disorders that commonly co-occur or are associated with MCAS and Mastocytosis?

Yes. There seems to be a greater risk of the following disorders:

  • AutismAutism
  • ADHD
  • Arthritis
  • Fibromyalgia
  • Lupus
  • Chronic Fatigue Syndrome
  • Interstitial Cystitis
  • Osteopenia/Osteoporosis
  • IBS
  • Chronic Lyme Disease
  • Anaphylaxis
  • Cystic Acne
  • Vertigo
  • Diabetes
  • Hypertension
  • Multiple Chemical Sensitivity (MCS)MS
  • Periodontal disease
  • Macular Degeneration
  • Multiple Sclerosis
  • Addison’s Disease
  • Restless Leg Syndrome
  • Anemia
  • Eosinioiphilic esoophagitis
  • Mitral valve prolapse
  • Vascular dementia


What causes MCAS or histamine intolerance?

That’s the million dollar question. This is what is known:

  • Mast cells are activated inappropriately.  In other words, there is an exaggerated response with the mast cells releasing more histamine than needed.  Also, histamine is released in circumstances where it would not normally be needed, e.g. certain foods, or even sunlight.
  • Symptoms seem to wax and wane over the years.  For example, an individual may experience symptoms during adolescence that eventually decline only to be bombarded ten years later with even worse symptoms.
  • There seems to be a genetic component that gets triggered by environmental insult(s).  In other words, research shows that MCAS and Mastocytosis tend to run in families, and the disorder is epigenetic.  The specific environmental insults that can trigger MCAS are not well understood.  Some research is showing that environmental mercury is one possible cause of MCAS.


What is the treatment for MCAS?

There is no definitive cure for MCAS or Mastocytosis at this time. However, there are many ways to manage the symptoms.

  1. Avoid any known triggers.  Some of the most common triggers are alcohol, cheese, aspirin, smoke, opiates, NSAIDs, cough suppressants, bacterial toxins, shellfish, strawberries, egg whites, tomatoes, nuts, insect bites, and infections.  (For a more complete list, go here.)
  2. Eat a low histamine diet.  (Download the diet here.)  There is a lot of disagreement as to the foods one must Low Histamine Chefavoid on a low histamine diet, but you can begin with this document, and branch out from there.)
  3. Take mast cell stabilizers such as Ketotifen.  (This medication can also help relieve symptoms of IBS.)  This medication requires a prescription.  You can purchase Ketotifen eyedrops over the counter.
  4. Use breathing medication as necessary.
  5. Take sublingual, liposomal, or injected methylcobalamin (B12).
  6. Take antihistamines.  Some require a prescription. Others, such as Benadryl, can be obtained over the counter.
  7. Use eye lubricants for dry eyes and excessive tear production.
  8. If experiencing depression, tricyclic antidepressants are excellent antihistamine medications, especially doxepin (Sinequan) and amitriptyline (Elavil).  These will also help with anxiety.
  9. If experiencing anxiety and/or tachycardia, low doses of benzodiazepines (e.g. Ativan, Xanax) work well as does mirtazapine (Remeron).  Benzodiazepines acts as antihistamines and also work directly on the mast cells.  They are, however, addictive, and they are hard to discontinue, so mirtazapine would be a better choice if it works for you.  These medications require a prescription.
  10. Quercitin is a natural antihistamine.  This supplement is available over the counter.curcumin
  11. Pancreatic enzyme supplements are helpful for digestive symptoms.  These are available over the counter.
  12. Curcumin inhibits mast cell activation.  Curcumin is available over the counter.
  13. Pycnogenol inhibits the release of histamine from mast cells.  Pycnogenol is available over the counter.
  14. Propolis inhibits histamine release.  Propolis is available over the counter.

References

Afrin, L.B. (2013).  Presentation, diagnosis, and management of mast cell activation syndrome.  In Mast Cells (Ed., David B. Murray), Hauppauge, NY: Nova Science Publishers.

Afrin, L.B. & Molderings, G.J. (2014).  A concise, practical guide to diagnostic assessment for mast cell activation disease.  World Journal of Hematology, 3(1), 1-17.

Akin, C., Valent, P., & Metcalfe, D.D. (2010).  Mast cell activation syndrome:  Proposed diagnostic criteria.  Journal of Allergy & Clinical Immunology, 126(6), 1099-1104.

Alvarez-Twose, I., Gonzalez de Olano, D., Sanchez-Munoz, L., et al. (2010).  Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms.  Journal of Allergy & Clinical Immunology, 125(6), 1269-1278.

Baek, O., Kang, O., Choi, Y., et al. (2003).  Curcumin inhibits mast cell activation.  Clinica Chimica Acta, 338(1-2), 135-141.

Christy, A.L. & Brown, M.A. (2007).  The multitasking mast cell:  Positive and negative roles in the progression of autoimmunity.  The Journal of Immunology, 179, 2673-2679.

Haenisch, B., Frohlich, H., Herms, S., & Molderings, G. J. (2014).  Evidence for contribution of epigenetic mechanisms in the pathogenesis of systemic mast cell activation disease.  Immunogenetics, 66, 287-297.

Horny, H.P., Sotlar, K., & Valent, P. (2012).  Evaluation of mast cell activation syndromes: Impact of pathology and immunohistology.  International Archives of Allergy and Immunology, 159, 1-5.

Lucas, H.J., Brauch, C.M., Settas, L., & Theoharides, T.C. (2006).  Fibromyalgia – New concepts of pathogenesis and treatment.  International Journal of Immunopathology and Pharmacology, 19(1), 5-9.

Molderings, G.J., Brettner, S., Homann, J., & Afrin, L.B. (2011).  Mast cell activation disease: A concise practical guide for diagnostic workup and therapeutic options.  Journal of Hematology & Oncology, 4, 10.

Molderings, G.J., Haenisch, B., Bogdanow, M. et al. (2013).  Familial occurrence of systemic mast cell activation disease.  Plos One, 8(9), e76241.

Molderings, G.J., Meis, K., Kolck, U., Homann, J., & Frieling, T. (2010).  Comparative analysis of mutation of tyrosine kinase kit in mast cells from patients with systemic mast cell activation syndrome and healthy subjects.  Immunogenetics, 62, 721-727.

Murali, M.R., Catells, M.C., Song, J.Y., et al. (2011).  Case 9-2011: A 37-year-old man with flushing and hypotension.  New England Journal of Medicine, 364, 1155-1165.

Picard, M., Giavina-Bianchi, P., Mezzano, V., & Castells, M. (2013).  Expanding spectrum of mast cell activation disorders: Monoclonal and idiopathic mast cell activation syndromes.  Clinical Therapeutics, 35(5), 548-562.

Rama, T.A., Corte-Real, I., Gomes, P.S., Escribano, L., & Fernandes, M.H. (2010).  Mastocytosis: Oral implications of a rare disease.  Journal of Oral Pathology & Medicine, DOI: 600-0714.2010.

Sant, G.R., Kempuraj, D., Marchand, J.E., & Theoharides, T.C. (2007).  The mast cell in interstitial cystitis: Role in pathophysiology and pathogenesis.  Urology, 69, Suppl 4A, 34-40.

Schramm, R. & Thorlacius, H. (2004).  Neutrophil recruitment in mast cell-dependent inflammation: Inhibitory mechanisms of glucocorticoids.  Inflammation Research, 53(12), 644-652.

Sharma, S.C., Sharma, S., & Gulati, O.P. (2003).  Pycnogenol inhibits the release of histamine from mast cells.  Phytotherapy Research, 17(1), 66-69.

Shinmei, Y., Yano, H., Kagawa, Y., et al. (2009).  Propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.  Immunopharmacology & Immunotoxicology, 31(4), 688-693.

Sonneck, K., Florian, S., Mullauer, L., et al. (2007).  Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: Monoclonal mast cell activation syndrome.  International Archives of Allergy and Immunology, 142, 158-164.

Theoharides, T.C. (2014).  Mast cells in irritable bowel syndrome and ulcerative colitis: Function not numbers is what makes all the difference.  Digestive Diseases & Sciences, DOI 10.1007/s10620-013-2988-z.

Theoharides, T.C. (2013).  Extracellular mitochondrial components secreted from activated live mast cells act as “innate pathogens” and contribute to autism pathogenesis.  International Trends in Immunity, 1(2), 5-10.

Theoharides, T.C., Asadi, S., Panagiotidou, S., & Weng, Z. (2013).  The “missing link” in autoimmunity and autism: Extracellular mitochondrial components secreted from activated live mast cells.  Autoimmunity Reviews, http://dx.doi.org/10.1016.jautrev.2013.06018.

Theoharides, T.C., Asadi, S., & Panagiotidou, S. (2012).  A case series of a luteolin formulation (Neuroprotek) in children with autism spectrum disorders.  International Journal of Immunopathology and Pharmacology, 25(2), 217-323.

Valent, P. (2013).  Mast cell activation syndromes: Definition and classification.  European Journal of Allergy and Clinical Immunology, 68, 417-424.

Valent, P., Akin, C, Arock, M., et al. (2011).  Definitions, criteria and global classification of mast cell disorders with special reference to mat cell activation syndromes: A consensus proposal.  International Archives of Allergy and Immunology, 157, 215-225.

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