Question

PATIENT MEDICAL HISTORY

Georgia is a 32 year old woman who has been suffering from recurrent (sometimes severe) headaches, and periods of fatigue since late childhood (~10-11 years of age). In her early twenties (21 years of age) she was diagnosed with gastroesophageal reflux disease (GERD) and began to experience periods of unexplained abdominal pain.

Georgia’s symptoms have waxed and waned over times, sometimes she feels fine but other times (since ~10-11 years of age) the headaches, fatigue and abdominal pain (since ~21 years of age) seem overwhelming. Lately the fatigue and abdominal pains have been particularly bad.

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

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

Georgia feels tired all of the time; the amount of sleep she gets does not seem to lessen the fatigue. She finds mornings especially difficult but fatigue is present throughout the day. She finds it difficult to concentrate and her performance at work has begun to suffer. She sometimes feels too tired to climb the stairs to her second floor apartment.Her doctor sent her to a sleep clinic but an overnight sleep observation study did not find anything abnormal.

While Georgia is most concerned with the abdominal pain and fatigue 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 other areas of the skin with no cause; different from blushing which is usually milder and caused by emotions such as embarrassment)

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

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

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

• Mild and transient leukocytosis (transient = in blood drawn at some 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 of PGD2 (prostaglandin D2)

How might an immune response contribute to:

• Q1a) Dermatographism?

• Q1b). Abdominal pain?

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

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

Basically Georgia’s mast cell responses are too strong which could be because she has too many mast cells, her mast cells are hyperactive or both. Since her doctor has ruled out mastocytosis there are not an abnormal number of mast cells

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

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

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

Q1f). Based on your answers above describe the link between aberrant (too strong) mast cell responses and chronic multi-system inflammation .

Answer 1

Q1a).DERMATOGRAPHISM.Is also known as dermographism simply translate" writing on the skin" .It is very common localized hive reaction ,affecting approximately 2-5%of the general population .This condition is characterized by the abrupt onset of welts and hives where the akin is exposed to pressure,scratching,itching or stroking ..DERMATOGRAPHISM is frequent diagnosed incidentally,especially in relation to other skin disorders like eczema.

Q1b)ABDOMINAL PAIN:chron's disease and ulcerative colitis are the other conditions that may cause lower abdominal pain.These diseases are caused by inflammation in the intestinal tract.The body's immune system attacks the lining of the intestine .Besides abdominal pai ,other symptoms include diarrhoea,bloody stools,fatigue,fever,malnutrition and weight loss.

Specialized x-ray can diagnose inflammatory bowel disease .steroids and medicines ,which suppress the immune response ,are helpful in managing IBD inflammatory bowel disease

Q1C)tryptase ​​​​is an enzyme that is related along with histamine and other chemicals,from mast cells when they are activated as part of a normal immune response as well as in allergic responses .This test measures the amount of tryptase in the blood .

Q1D)granulocytes are white blood cells that help the immune system fight off infection they have a characterized morphology having large cytoplasmic granules,that can be strained by basic dyes and a bi-lobed nucleus .Typically granulocytes have a role both in initiative and adaptive immune responses in the fight against viral and parasitic infections . They migrate and release a number of efficient effector molecules,including histamines ,cytokines,enzymes,and growth factors .As a result granulocytes are an integral part of inflammation and have significant role in the allergies .

Q1e)mast cells located in connective tissue,including the skin,the lining of the stomach and intestine,and other sites.They play an important role in helping defend these tissues from disease.