September 2014: Post summaries and take home points

Effects of estrogen and progesterone and the role of mast cells in pregnancy

  • Estrogen and progesterone have many functions in the reproductive system and outside of the reproductive system.
  • The activity of progesterone is amplified by estrogen.
  • Estrogen levels can make cells more responsive to progesterone.
  • Mast cells express receptors for both estrogen and progesterone.
  • Estrogen and progesterone both induce mast cell degranulation individually.
  • Estrogen and progesterone together induce more mast cell degranulation.
  • During pregnancy, secretion of histamine by uterine mast cells is induced.
  • Mast cell degranulation increases uterine contractility.
  • Allergic reactions can induce uterine contractions.
  • Severe allergic reactions may be responsible for pre-term labor.
  • Asthmatic pregnant women are at higher risk of pre-eclampsia.
  • 30-40% asthmatic women have more symptoms during premenstrual period.
  • Women taking hormone replacement have higher risk of new onset asthma.
  • Many women with mast cell disease report more degranulation when menstruating.
  • A 2011 study found that only 6.7% of women with SM delivered prematurely, compared to 7.4% in the general population.

Mastocytic enterocolitis

  • First named in 2006.
  • Refers to having increased mast cells in the GI tract mucosa.
  • Usually causes chronic diarrhea and abdominal pain.
  • Increase in mast cells not associated with SM or CM.
  • The original paper defined mastocytic enterocolitis as more than 20 mast cells/hpf.
  • However, there is not a consensus on what is a “normal” amount of mast cells in the GI mucosa.
  • Some healthy controls have more than 20 mast cells/hpf.
  • Some MCAS patients have mast cell counts in GI tract of 17-23/hpf.

Gastrointestinal manifestations of SM: Part 1

  • 80% of SM patients experience GI symptoms.
  • 11% have GI bleeding.
  • Abdominal pain in SM is usually either upper abdominal pain or lower abdominal cramping.
  • 23% of SM patients have peptic ulcer disease.
  • 85-100% of SM patients have elevated histamine production.
  • Some SM patients produce too much acid, some too little, and some normal amount.
  • In those who overproduce, the levels can be extremely high.
  • 28% of SM patients have esophageal abnormalities.

Gastrointestinal manifestations of SM: Part 2

  • Thought that at least 30% SM patients have abnormalities in small bowel.
  • Many types of abnormalities in GI biopsies of SM patients.
  • 5-25% of SM patients have malabsorption due to small intestine defects.
  • One study found 67% of SM patients have elevated fat excretion in feces.
  • SM patients may have malabsorption of fat soluble vitamins.
  • 20% of SM patients have colon abnormalities.
  • 19% of SM patients have had diverticulitis.
  • Elevated PGD2 may cause diarrhea.

MCAD, MCAS and the hierarchy of mast cell disease classifications

  • MCAD (mast cell activation disease) is a catch-all term for mast cell disease.
  • MCAS (mast cell activation syndrome) is the diagnosis you get if you have evidence of elevated mediator release but don’t meet the criteria for other mast cell diseases.
  • If you have UP: you have UP, you have CM, you have MCAD.
  • If you have TMEP: you have TMEP, you have CM, you have MCAD.
  • If you have SM: you have SM, you have MCAD.
  • If you have SM with UP: you have SM with skin involvement, you have UP, you have MCAD.
  • If you have SM with TMEP: you have SM with skin involvement, you have TMEP, you have MCAD.
  • If you have SM-AHNMD: you have SM-AHNMD, you have MCAD.
  • If you have ASM: you have ASM, you have MCAD.
  • If you have MCL: you have MCL, you have MCAD.
  • If you have MCAS: you have MCAS, you have MCAD.

Neurologic symptoms of mast cell disease

  • Syncope (fainting) affects 14.3% of mastocytosis patients.
  • 6% had back pain.
  • Compression fracture is a common cause of back pain.
  • 35% had headaches.
  • Some mastocytosis patients have migraines.
  • Trigeminal neuralgia has been reported in some patients.
  • 3% of mastocytosis patients develop multiple sclerosis, compared to 0.1% of the general population.

Mast cell disease and chronic constipation

  • Diarrhea or constipation can affect mast cell patients.
  • In one study, 57% of SM patients reported at least two pseudoobstructions a year.
  • Bowel retraining is a good option for managing chronic constipation.
  • People with chronic constipation may have pelvic floor dysfunction.
  • Pelvic floor PT may help.
  • Anorectal manometry and bowel transit time tests are helpful for identifying a cause for constipation.
  • Straining to stool causes long term nerve damage, hemorrhoids, bleeding and fissures.
  • Bowel obstructions can cause rupture and are serious.
  • Many mast cell medications slow GI motility, complicating the constipation issue.

Mast cell look alikes

  • A number of conditions present similarly to mast cell disease.
  • Carcinoid tumors are slow-growing neuroendocrine tumors that may release excessive serotonin.
  • Carcinoid syndrome is diagnosed with a 24-hour urine test for 5-HIAA, a metabolite of serotonin.
  • Pheochromocytomas are neuroendocrine tumors of the adrenal gland that secrete a lot of norepinephrine.
  • Pheochromocytoma is diagnosed with 24-hour urine test for catecholamines and metanephrines.
  • Medullary thyroid cancer produces excessive calcitonin.
  • Medullary thyroid cancer is diagnosed by serum calcitonin.
  • Dysautonomia is an inherent dysfunction of the autonomic nervous system, which can cause wide ranging symptoms.
  • Dysautonomia can be secondary to another condition, like mast cell disease, or a primary condition.
  • Primary asthma can cause airway symptoms.
  • Vocal cord dysfunction can cause airway obstruction.
  • Angioedema causes swelling of any part of the body. It can be hereditary or not.
  • Irritable bowel syndrome is a diagnosis of exclusion.
  • Mast cell disease is often mistaken for anxiety or panic attacks.

Hemolytic anemia

  • A type of anemia that causes abnormal destruction of red blood cells.
  • This causes the body to break down more hemoglobin than usual.
  • Can cause high concentration of reticulocytes (immature red cells) in the blood.
  • Can have many causes, including genetic issues, certain infections, and autoimmune disease.
  • Diagnosed with blood smears. Further testing can reveal specific type.
  • Transfusions can be required in severe cases.
  • If autoimmune, long term steroids or spleen removal are sometimes necessary.