Myelodysplastic syndrome (MDS)
- Umbrella term for disorders in which body does not produce enough myeloid cells and the cells produced do not function correctly.
- Myeloid cells are a type of white cells including eosinophils, basophils, neutrophils and mast cells.
- MDS patients have low blood counts.
- Sometimes asymptomatic.
- Spleen is often swollen.
- Bone marrow biopsy is diagnostic.
- There are a number of causes of MDS.
- Stem cell transplant may be considered in severe cases.
- Transplant has 50% survival after 3 years.
- Majority of MDS patients progress to acute myeloid leukemia (AML).
- 23% of SM-AHNMD have SM and MDS.
Cutaneous mastocytosis and systemic symptoms
- Urticaria pigmentosa (UP) and telangiectasia macularis eruptiva perstans (TMEP) are forms of cutaneous mastocytosis (CM).
- CM is caused by dense infiltrates of mast cells in the skin.
- Skin is the organ most likely to be infiltrated by mast cells.
- Patients with UP or TMEP who do not have SM can still have symptoms affecting organs other than the skin.
- CM patients can have shortness of breath, low blood pressure, nausea, vomiting, diarrhea and other mast cell symptoms.
- Mast cell mediators release in the skin can move through the tissue and trigger other mast cells.
- The more skin covered by rash, the more likely systemic reactions are.
- Having systemic symptoms does not mean you have SM.
- If you develop CM as an adult, you are likely to develop SM.
- Chronic elevation of tryptase, expression of CD25 by skin mast cells or presence of D816V CKIT mutation can indicate SM will develop.
- Systemic symptoms in CM are treated the same way as in SM or MCAS.
- MCAS does not refer to a state of reactivity or severe symptoms.
The question I get asked the most
- SM is not cancer.
- It is not cancer because the cells do not proliferative enough to endanger life.
- Most SM patients have indolent disease, for which life expectancy is normal.
- ASM has more features in common with cancer.
- MCL is cancer.
Anticholinergic effects of mast cell medications
- Anticholinergics block the molecule acetylcholine from sending signals in the central and peripheral nervous sytems.
- Blocking acetylcholine can cause many side effects, including:
- Decreased GI motility
- Dry mouth and throat
- Dilation of pupils
- Rapid heart rate
- Visual disturbances
- Urinary retention
- Cognitive issues
- Myoclonic jerks
- A lot of antihistamines are anticholinergics.
- Cyproheptadine, promethazine, desloratadine, loratadine, diphenhydramine, clemastine, doxepin, doxylamine, ipratropium, hydroxyzine and meclizine are anticholinergics.
- Alprazolam, diazepam, ranitidine, prednisone and hydrocortisone may be anticholinergics.
- Cetirizine and fexofenadine are not anticholinergics.
- Many allergic conditions are exacerbated by menses.
- Sex hormones influence mast cell activation and degranulation.
- Mastocytosis patients often discontinue antihistamine and antimediator medications during pregnancy.
- During pregnancy, 45% of mastocytosis patients had itching, 40% had flushing, 24% had GI symtpoms, 9% had anaphylaxis.
- 22% had worsened symptoms throughout pregnancy.
- 18% developed new symptoms.
- 33% had improved symptoms during pregnancy.
- 15% had complete resolution of symptoms.
- All resolutions occurred during the first trimester and most lasted throughout the pregnancy.
- Anaphylaxis during pregnancy was resolved without epinephrine.
- 45% had no change in symptoms during pregnancy.
- Anesthesia and medications for labor were safe in mastocytosis patients.
- Premedication at initiation of labor is recommended.
- Rate of prematurity and birth complications were similar to general population.
Histamine effects on neurotransmitters (serotonin, dopamine and norepinephrine)
- Medications that block the H1 receptor increase dopamine release.
- Histamine stimulates prolactin release via the H2 receptor, which inhibits dopamine production.
- Histamine can increase metabolism of norepinephrine, serotonin and dopamine.
- About 40% of serotonin released by mast cells.
- Serotonin causes many GI symptoms.
- Mast cells release dopamine.
- Frequent mast cell activation decreases dopamine production.
- Dopamine can be converted to norepinephrine.
- Dopamine is responsible for cognitive alertness.
- Norepinephrine is responsible for concentration and vigilance.
- Increased histamine increases norepinephrine production and secretion.