PATIENT MEDICAL HISTORY

Georgia is a 32 year old woman who has been suffering fromrecurrent (sometimes severe) headaches, and periods of fatiguesince late childhood (~10-11 years of age). In her early twenties(21 years of age) she was diagnosed with gastroesophageal refluxdisease (GERD) and began to experience periods of unexplainedabdominal pain.

Georgia’s symptoms have waxed and waned over times, sometimesshe feels fine but other times (since ~10-11 years of age) theheadaches, fatigue and abdominal pain (since ~21 years of age) seemoverwhelming. Lately the fatigue and abdominal pains have beenparticularly bad.

Georgia is afraid to eat because she does not know when theabdominal pain will strike or what is causing it. She has begun tolose weight but her food restriction has not addressed the pain.Regardless of whether she has eaten a large or small meal, andregardless of ingredients the pain can occur.

Georgia’s doctor performed several tests and noticed symptoms ofinflammation in some areas of the intestine, after ruling out otherconditions her doctor has suggested Georgia may have InflammatoryBowel Disease (IBD). However, IBD would not explain why Georgiasometimes experiences upper abdominal pain or why the location ofthe pain seems to move around different areas of the abdomen.

Georgia feels tired all of the time; the amount of sleep shegets does not seem to lessen the fatigue. She finds morningsespecially difficult but fatigue is present throughout the day. Shefinds it difficult to concentrate and her performance at work hasbegun to suffer. She sometimes feels too tired to climb the stairsto her second floor apartment.Her doctor sent her to a sleep clinicbut an overnight sleep observation study did not find anythingabnormal.

While Georgia is most concerned with the abdominal pain andfatigue she has other symptoms as well:

• Mild cognitive dysfunction (“brain fog”)

• Dermatographism

• Inflammation and pain in several joints (hips, knees, elbows,hands/fingers) and lower back pain

• Occasional flushing (noticeably red face and sometimes otherareas of the skin with no cause; different from blushing which isusually milder and caused by emotions such as embarrassment)

• Occasional diaphoresis (excessive sweating for no apparentreason usually across the whole body or multiple areas of thebody)

• Occasional mild dyspnea (shortness of breath; feeling like youcan’t get enough air)

Georgia’s doctor has consulted some colleagues who recommended afull blood work up and tests to measure the levels of some keyimmune response molecules. Georgia’s tests show the following:

• Mild and transient leukocytosis (transient = in blood drawn atsome times but not others)

• Mild and transient elevated serum total tryptase level(transient = in blood drawn at some times but not others)

• Elevated urinary histamine metabolites and urinary levels ofPGD2 (prostaglandin D2)

How might an immune response contribute to:

• Q1a) Dermatographism?

• Q1b). Abdominal pain?

Q1c). What common immune response involves all of themarkers elevated in Georgia’s tests: tryptase, histamine andprostaglandin D2 (1 mark)?

After reviewing her tests Georgia’s doctor concludes she hasMast Cell Activation Syndrome (MCAS), a diseasecharacterized by chronic multi-system inflammation. Her doctorrules out mastocytocis (accumulation of mast cells).

Basically Georgia’s mast cell responses are too strong whichcould be because she has too many mast cells, her mast cells arehyperactive or both. Since her doctor has ruled out mastocytosisthere are not an abnormal number of mast cells

We initially looked at white blood cells commonly found incirculation and therefore when it came to granulocytes focused onbasophils, eosinophils and neutrophils. Mast cells are alsogranulocytes though not found in large numbers in circulation.

Q1d). What do granulocytes all have in common both instructure and in immune response roles ?

Q1e). If they aren’t in circulation then where in thebody are mast cells located (1 mark)?

Q1f). Based on your answers above describe the linkbetween aberrant (too strong) mast cell responses and chronicmulti-system inflammation .