April 2015: Post summaries and take home points

Urticaria is the medical term for hives.
Hives are usually called by allergic processes, but can occur for other reasons.
Angioedema is swelling in the dermis, subcutaneous tissue, mucosa and submucosa. It is sort of “inside hives”.
Angioedema can be dangerous, especially if it affects the airway.
Urticaria and angioedema are closely related.
If acute, they last for less than six weeks. If chronic, they last for more than six weeks.
Acute urticaria is usually due to activation of mast cells and basophils.
Antihistamines and brief courses of steroids usually manage acute urticaria.
Chronic urticaria usually does not have an identifiable cause.
CU patients can have urticaria and angioedema, either alone or together.
Cutaneous mast cells drive CU and histamine is the most important mediator.
CU is rarely IgE mediated.
CU is associated with several chronic conditions, including autoimmune diseases, neoplastic diseases and thyroid disease.
30-50% CU patients make IgG antibodies to the IgE receptor.
5-10% CU patients make IgG antibodies to the IgE molecule.

CU lesions are swollen pink or red wheals of variable size, sometimes with surrounding redness.
CU lesions are itchy rather than painful or burning.
Angioedema is not itchy, is non-pitting and without redness.
Physical urticarias are triggered by environmental sources. There are many types.

Prostaglandin E2 has inflammatory and anti-inflammatory effects in the body.
PGE2 induces fevers and has many other functions.
PGE2 can cause mediator release from mast cells.
PGE2 can enhance IgE production by B cells.
PGE2 relaxes the smooth muscle and opens the airway.
When asthmatics take NSAIDs, their asthma often worsens due to interfering with production of PGE2.

Mast cell mediators: PGD2

Prostaglandin D2 is the dominant prostaglandin made by mast cells.
It has many functions, including regulation of sleep and perception of pain.
9a,11b-PGF2a is a breakdown product of PGD2. Both can be tested for in urine as markers of mast cell disease.
PGD2 is a strong bronchoconstrictor and is important in asthma.
PGD2 is involved in nerve pain via the COX-1 pathway.
Aspirin is commonly used in mast cell patients to inhibit production of PGD2. This protects against PGD2 from both COX-1 and COX-2 pathways.
PGD2 causes characteristic mast cell flushing.

Prostaglandins, thromboxanes and leukotrienes are all types of eicosanoids.
Eicosanoids are made from arachidonic acid.
COX-1 and COX-2 are enzymes that make prostaglandins.
5-LO (lipoxygenase) makes leukotrienes.
Non steroidal anti-inflammatories interfere with COX-1 and/or COX-2, depending on the medication. This interferes with production of prostaglandins.
Zileuton is a lipoxygenase inhibitor and interferes with production of leukotrienes.

Mast cell stabilizers interfere with structures on the cell membrane that prevent with release of mediators.
Beta-2 adrenergic agonists relax smooth muscles and open airways.
Leukotriene receptor antiagonists interfere with function of leukotrienes.
5-lipoxygenase inhibitors prevent production of leukotrienes.
Corticosteroids interfere with activity of mast cells and production of mediators.
Proton pump inhibitors reduce gastric acid.

H1 antihistamines turn off the H1 receptor. This helps with many symptoms.
H2 antihistamines interfere with action of the H2 receptor. This helps mostly with GI symptoms, but also skin symptoms.
H3 antihistamines modulate nerve pain and may normalize levels of neurotransmitters like serotonin.
While three medications are known to have H3 activity, they are not designed for this purpose and have serious risks.
Thioperamide is promising as an H3 and H4 blocker, but is not yet available for patient use.

A neoplasm is an abnormal group of cells.
SM is a neoplasm.
Receptors are proteins on the outside of cells that bind specific molecules. This causes a specific action to occur.

CD117 (CKIT) is a normal marker found on the outside of mast cells.
CD117 is sometimes not seen on the outside of mast cells in biopsies because the test is not very sensitive.
Being CD117 positive in a biopsy is not the same as being CKIT positive.
Being CKIT positive affects options for chemotherapy and disease classification.
CD25 and CD2 are abnormal markers on the outside of mast cells linked to SM.
CD30 is sometimes positive on mast cells in SM.
CD34 is a marker of cells that become mast cells, and on new mast cells.

Mast cells cause formation, progression and destabilization of atherosclerotic lesions.
Mast cell released histamine can cause coronary spasms.
Histamine can cause acute coronary vasoplasm that results in heart attack. This is called Kounis Syndrome.

Some H1 antihistamines have anti-inflammatory properties.
They reduce eosinophil accumulation near allergic sites.
Some H1 antihistamines inhibit bradykinin induced formation of hives.
H1 antihistamines have also inhibited allergy processes of methacholine and platelet activating factor.

When histamine binds to the H1 receptor, it keeps the receptor “turned on”, causing symptoms.
H1 antihistamines prevent histamine from “turning on” the H1 receptor.
First generation H1 antihistamines cross the blood-brain barrier, which can interfere with sleep-wake cycle, memory, cardiovascular regulation and cause other effects.
First generation H1 antihistamines also bind to other types of receptors.
Second generation H1 antihistamines only bind to the H1 receptor.
Second generation H1 antihistamines do not cause sedation or the neurologic issues seen in first generation H1 antihistamines.

The circadian clock is the “body’s clock”. It tells the body what to do on a 24 hour cycle.
Mast cells and eosinophils have internal clocks.
Allergic symptoms, including pulmonary ones, are worse between midnight and morning, with onset around 10pm.
This causes sleep disruption, morning attacks”, poor rest and decreased quality of life.
Circadian rhythm affects mast cell mediator release.
Tryptase and histamine are lower in the afternoon and higher at night.
A signal from adrenal glands “starts the clock”.

Some organisms decrease mast cell mediator release.
Some of these organisms can cause disease and some are harmless.
Lactobacillus and Bifidobacteria are healthy bacteria that inhibit mast cell degranulation and activation.