Tests

 

 

So to begin

 

Mast cell conditions

We begin with excluding basic allergies

- RAST -Blood test for levels of antibody IGE for a specific allergen

- Patch testing -were suspect allergens are left next to the skin

- Prick testing - were a suspected allergen is put on the skin then pricked through and a reaction is watched for

In most patients suspected of a mast cell condition the results of these tests will not explain all the symptoms

 

Rast can be done on antihistamines . The other test can't . Letters from allergists say to stop meds for your apponintment

This SHOULD NOT be done , if you have had any concerning symptoms -Which I class as any airway symptoms or symptoms of anaphylaxis or near to anaphylaxis . Its better to get to the appointment without having a reaction than to end up in A&E /ER.

 

Differential Diagnosis - Medical word for establishing a diagnosis by excluding conditions which present very similarly

 

Tests and working out what is going on

Download -

Then Testing for Mastocytosis -

 

Antihistamines do not affect tryptase or histamine or prostaglandin tests. Mast cell stabilisers can but DO NOT STOP any medications. As your on them for a reason  . The doctor will interpret your results based on your medications .

 

This is a blood test for mast cell tryptase which should be below 20 . This should be taken on a normal day and within 2 hours of an event/ anaphylaxis . The body processes Tryptase quickly ( Schwartz 2005 & UK resisuitaion guidelines 2008 )

If both of these are negative then Systemic Mastocytosis is unlikley but possible -  15 % of patients with systemic mastocytosis have normal tryptase .(           )  2 links are to a paper with a patient in this situation and a personal account .

 

In a patient with normal tryptase presence of skin mastocytosis - CM , urticaria pigmentosa  and or changes in blood numbers - red and white cells would stimulate a doctor to do a bone marrow biopsy .

 

If it is positive over 20 a bone marrow biopsy is needed. These are done with lots of sedation ideally by aheamotologist who does them every day  .

 

IMPORTANT -These samples need examining by a hospital that specliase in examining bone marrow samples for mast cell as the testing process is very specific .

If other organs have symptoms - bowel, liver, spleen then samples should be taken and examined in the same way in a speclast centre . The normal number of mast cells in the bowel were defined at american GI conference 2014 .

 

 

 

en3) Autoimmune mast cell activation

In auto - immunity - were the immune sytem attacks the bodys own cells as if they are bad or non self -

This leads to continious compliment cascades happening  - this leads to a group of chemicals building up called anaphlatoxins ( see anaphylaxis ) and mast cell activation .

 

Many autoimmune conditions have antibodies -which couple with compliment to open mast cells and also produce more anaphlatoxins

 

Common autoimmunes which are known to cause this are- hashimotos thyroiditis , adrenal autoimmunity, lupus, amiloydosis

 

Symptoms are as for direct mast cell activation conditions . Treatment is as for any cause of mast cell activation to treat symptoms .

 

The autoimmunity is treated with with immunosurpressants / Immunemodulation . Raised basophil histamine is a indicator of autoimmune histamine production and so acts as a sign of positive treatment outcomes to immune modulation.

 

Identifying and avoiding triggers remains vital. They can feel very difficult to work out due to the liklihood of triggering being dependent on the level of autoimmunity .

 

There can be an autoimmune condition where the body attacks its own ige - which should be checked for  

Things we notice - which is being researched. But as yet doesn't have explaintions . Some bioloical connections are seen but need research .

~  Its noted that in the 6 months before the symptoms emerge or become serious ( if minor symptoms existed before ) the person has expereinced a period of high stress ,an accident or an operation .

 

~ No direct genetic inherited pattern is currently known .The ckit mutataion in systemic mastocytosis -and other s on axon 17 - see        are not passed on or present at conception .This si even the case in identical twins .

 

~ But we see mast cell symptoms in families at varying levels .

 

~ Many conditions with previously unknown cuases are being shown to have mast cells involved .

 

~ The only rule in mast cell is it breaks its own rules .

 

~ Postural orthstaic tachycaria and Etherlos dnalos syndrome either alone ot together have food intolerences associated .These arent IGE allergies . These are being found to respond to mast cell medications . Research is beginning -there are some logical biological inks .I menation the connection were i discuss them and adownload is coming ;-) But -for now -these conditions should be traeted and diagnosed formally .Some sites advocate use of certain drugs-these are NOT mast cell trtaements but for treatmant of EDS .

 

~ Antihistamines are being found to help various conditions - fibromaygia (research under way ) , Chronic faigue syndrome (CFS ) some research complete some underway . follow link for an indepth discussion of known and proable links .

2) Kinin based angiodeama ( swelling )- this is not a mast cell condition but mimcs it.

 

It is heridatory angiodeama .

 

Is caused by an Inherited abnormal gene that causes a deficiency of a normal blood protein- complimet 1 inhibitor

 

3 types: Type 1 and II mutation of C1NH (SERPING1) gene on chromosome 11, encoding C1 inhibitor protein;

Type III mutation in F12 gene on chromosome 12, encoding coagulation factor XII.

 

Type 1 results in low levels and function of circulating C1 inhibitor; Type II has normal levels of C1 inhibitor protein but reduction in function

 

Type III is oestrogen dependant

 

Occurs in 1 in 50,000 males and females; Type III more severe in women.

 

Decreased C1 inhibitor activity leads to excessive kallikrein, which in turn produces bradykinin, a potent vasodilator

 

This does not have hives . It is tested for by looking to see if the level of c1 esterase inhibitor -which is compliment number 1 controlling enzyme - is low or not working properly .

 

It has all the symptoms and triggers of mast cell disease.

 

No hives

Anti histamines and steriods don't work

Swelling-anaphylaxis -tends to come on slower and last over 2-3 days then abate .

Has different treatment options

In the absence of any cause of the symptoms , 2 further conditions mimic mast cells . These are carciniod syndrome and pheocryocythoma

 

Carciniod is a rare very very slow growing cancer - over up to 10 years . It effects entrocromaffin cells -which are a part of your hormone system - they naturally put out many chemical in normal levels inc histamine , serotonin and adrenaline and may other chemicals .

 

By sharing serotonin and histamine with mast cell, symptoms are very similar .

 

General symptoms include - increased anxiety , itching, flushing , fast heart and high blood pressure day to day suddenly ,then settling.

 

Symptoms of carcinoid of the lung

1 in 4 people (25%) will not have any symptoms from the carcinoid tumour itself. If you do have symptoms, they may include

 

A cough

Coughing up blood (haemoptysis)

Wheezing

Breathlessness

Pain in the chest

Tiredness

Feeling sick

Weight gain

Sometimes a cough and wheezing may be confused with asthma. Some people get chest infections that don’t respond to treatment with antibiotics.

 

Symptoms of carcinoid of the stomach

If you have any symptoms, they are similar to those of other types of cancer of the stomach. They include

 

Pain

Weight loss

Fatigue (tiredness and feeling weak)

 

Symptoms of carcinoid of the bowel (including the appendix)

Most people with carcinoid of the bowel do not have any symptoms. If you get symptoms, they may include

 

Abdominal pain

Blockage of the bowel - you may have pain, constipation, watery diarrhoea, and feel or be sick

Bleeding from the back passage (rectum)

Some people find that they have vague symptoms for many years, which may include abdominal pain and a change in their bowel habit. Doctors sometimes diagnose these symptoms as irritable bowel syndrome, because irritable bowel syndrome is very common and carcinoid is very rare.

 

A surgon may find a carcinoid tumour accidentally, when taking out the appendix for appendicitis. They usually remove the tumour completely, along with the appendix. In this situation the tumour is often picked up at a very early stage and may need no other treatment.

 

Symptoms of carcinoid syndrome

Some carcinoid tumours produce large amounts of hormones and cause carcinoid syndrome. Carcinoid syndrome is a collection of symptoms. Your symptoms will depend on the hormone that your tumour is making and if the blood from the tumor siate passes through the liver before going into the main circulation .This is because the liver digests the enzymes . From the gut the blood goes directly to the liver  -so the chemicals are inactivated. In seconderies-in the liver or lung carciniod -the products get to cuase symptoms before the blood gets to the liver to be cleaned . So carciniod syndrome doesn't happen in all carciniod cases- approx 20% -but the presence of carciniod syndrome does not necesserily mean the disease has spread.

 

You may have

 

Flushing

Abdominal pain

Diarrhoea - this can be severe, some people have diarrhoea 15 or more times a day

Loss of appetite

Wheezing

Fast heart rate

Blood pressure that may go up or down - this can be triggered by having an anaesthetic.

 

Flushing

Most people who have carcinoid syndrome have flushing of their skin. Your face and neck become red and you feel warm and may itch. The flushing is often unexpected and unpredictable. Some people find that flushing is triggered by certain foods inc cheese , or drinking coffee or alcohol. Bending down ,stress or exercising can also trigger flushing.

 

Adapted from REF-

 

Having carcinoid syndrome can cause the following complications:

 

Carcinoid heart disease.

Some people with carcinoid syndrome develop carcinoid heart disease. Carcinoid syndrome causes a thickening of the heart valves, making it difficult for them to function properly. As a result, the heart valves may leak. Signs and symptoms of carcinoid heart disease include fatigue and shortness of breath during physical activity.  renin -also produced -cuases fibrosis of the heart muscle , reducing its ability to move . Carcinoid heart disease can eventually lead to heart failure. Your doctor may recommend medications for your heart. Surgical repair of damaged heart valves is the only treatment to correct carcinoid heart disease.

 

This is a point of difference from mast cell disease

 

Bowel obstruction. Cancer that spreads to the lymph nodes next to your small intestine can cause narrowing and kinking of your intestine, leading to a bowel obstruction.

 

Signs and symptoms of a bowel obstruction include severe, cramping abdominal pain and vomiting. Surgery may be necessary to relieve the obstruction.

 

Carcinoid crisis. Carcinoid crisis causes a severe episode of flushing, low blood pressure, confusion and breathing difficulty. Triggers include anesthesia, chemotherapy and other cancer treatments, though carcinoid crisis can occur for no apparent reason. Carcinoid crisis can be fatal. Your doctor may give you medications before surgery or chemotherapy to reduce the risk of carcinoid crisis.

 

REF-

 

It has to be tested for as it is so similar to masto that only tests can work it out .

 

The test is a 24hour urine of 5-H1AA - serotnin derivative and a blood for chromatogranin a .

 

FOODS TO AVOID DURING 24 HOUR URINE COLLECTION FOR 5-HIAA

Avocados, bananas, plums, walnuts, pineapples, tomatoes, aubergines, cough medicine. see list in the column to the right ------->

 

Some sites say the PPI - acid reducers - drug name-written in small or big on the box -omperazole. lansoprazole -name ending in zole -  medications can interfere with chromtogranin a results .I am going to look into this further ,It is not listed in the endocrinology bible by the UK top specliasts .

 

Levels dont have to high for a carciod to be present , because the liver metabolises alarge amount of the chemicals .

 

It can be found using an ocertide scan +/- MRI and removed on a set of meds.

 

Treatments - Endocrine bible -

 

The survival rate, even for disease which has moved to the liver is 85% at 5 yrs. Crisis has vv high BP .

 

EPIPENS are dangerous in carciniod syndrome . If this is highly suspected, Glucgaon should be prescribed for first line anaphylaxis treatment . if an epipen is needed it should be administered by medical personell to watch for potential hazards.

 

For the UK specalist centre , for carciniod and Pheocryocythoma information and doctor details follow the link .

 

The presence of Hpylori is associated with heriditory angiodeama ( Grattan 2005)

 

Acute episodes of hereditary angioedema do not respond to adrenaline, antihistamine and corticosteroids. Fortunately most acute episodes of Type I and II hereditary angioedema are non life-threatening.

 The mainstay of emergency medical treatment is intravenous C1 inhibitor concentrate (a blood product).

 If this is unavailable, fresh frozen plasma can be infused, but this occasionally exacerbates the angioedema.

 New medications inhibit bradykinin, e.g. icatibant, or kallikrein, e.g. ecallantide. Ecallantide has been reported to cause anaphylaxis in some cases.

 

The chance of an attack can be reduced with the following medications:

 

 C1 inhibitor concentrate infused an hour before a surgical procedure

 

 Anabolic steroids (stanazolol, oxandrolone and danazol) to increase circulating levels of normal functional C1 inhibitor. These have 'male-like' hormonal activity, so may cause weight gain, menstrual irregularities and virilism ( masclinistaion -hair ) .

 

 Tranexamic acid has been used in pre-pubertal children and may be effective in Type III herediary angioedema.

Pheocryocythoma  

- is a non cancer mass in the adrenals, which are glands above the kidneys .

 

Which give out stress hormones and adrenlaine /epiepherine ( the same substance )  and their opposites in function nor epinpeherine / nor adrenaline ,

 

Symptoms include -

High blood pressure not responding to medications ,

Flushing, sweating-point of difference from mast cell

High pulse not settled at night hwen the pulse should go down .

Anxiety with no logical cuase

 

The test is a 24 hour collection of urine for catelclamines . or blood taken from a line placed 2hrs before .

 

Some of the substances that can interfere with catecholamine testing include: paracetamol (acetaminophen), aminophylline, amphetamines, appetite suppressants, coffee, tea, and other forms of caffeine, chloral hydrate, clonidine, dexamethasone, diuretics, adrenaline, ethanol (alcohol), insulin, imipramine, lithium, methyldopa, MAO (monoamine oxidase) inhibitors, ACE inhibitors, nicotine, nitroglycerin, propafenone, reserpine, aspirin (salicylates), theophylline, tetracycline, tricyclic antidepressants, and vasodilators.

 

The effects of these drugs on catecholamine results will be different from patient to patient and are often not predictable. Bananas, pineapple and capsicums may also cause falsely elevated catecholamine results and should be avoided for 24 hours before and during the urine collection.

 

It can be found with mri and removed with complete recovery . This must be covered with alpha and beta blocking drugs because when the pheo is touched it releases epipeherine and nor epinepeherine.

 

NOTE - CT CONTRAST IS BAD FOR MAST CELL CONDITIONS AND PHEOCRYOCYTHOMAS . MRI is preferred but cover with the protocol for procedures is advised. more on this later ;-)

 

Gastroparesis of unknown origin is associsted with Pheo's .it also has genetic element

 

 

acid secretion F6.large entrocromaffin cells

In the absance of any positive results to the other possibilities . The condition will be labelled idiopathic -

 

The new diagnosis -Mast cell Activation Syndrome - Current standing diagnosis - Angiodeama ( swelling and urticaria ( hives )

 

50% of idioapthic angiodeama is autoimmune in origin

 

The presence of anaphylaxis would lead to a diagnosis od Idiopathic mast cell activation syndrome with anaphylaxis

 

The current diagnosis being -Idiopathic Anphylaxis

 

Propsed New diagnosis can take time to be used universally, So this is why I am referring to both

 

HAE points of differnce in clinical presentation and treatments

Heridetary Angiodeama  (HAE)

Carciniod syndrome and tumors

Points of difference

Carciniod heart disease demontstrated as valve disease particulalry bicuspid ( right )

 

Hypertension in crisis and hyperglycemia  -not to be confussed with compensated shock .

 

Otherwise can only be told apart by testing

Pheocryocythoma

Points of difference

Hypertension uncontrolled by antihypertensives

 

Tachycardia constant even when patient is asleep

So - testing . Medicine has a saying - If you hear hoofs think horses not zebras - ie the simple diagnosis is most likley and rule these out first .

 

Having got this far you are likley to have met a number of doctors for who you didnt fit into their boxes . All Doctors have a clutch of boxes - diagnoses . They have some common ones-which we call horses -It looks like a horse and sounds like a horse - so its a horse . But they also have small number of zebras- It looks like a horse and sounds -mostly - like a horse but its not xxx

 

As a result of the dance of the specialists , you will likley have clutch of horses or each specailities version of a virus xx- yes, you have symptoms but you aren't either one or our horses or zebras - examples- IBS , non specific headaches .

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874294/
Link button
http://www.imperialendo.co.uk/Bible2010v1.htm#_Toc215869326 http://www.imperialendo.co.uk/Bible2010v1.htm

The endocrine bible

 

These are -

Acid phosphatase

 

α-glycoprotein

 

α1-antitrypsin

 

Amylin

 

Atrial natriuretic polypeptide -causes heart valve problems

 

Calbindin-D28k

 

Catecholamines - adrenaline / noradrenaline (epinepherie nor epinepherine

 

Chromogranin A and B (CgA/CgB)-Tested

 

Dopamine

 

Fibroblast growth factor (FGF)

 

Gastrin

 

Gastrin-releasing peptide (bombesin)

 

Glucagon/glicentin

 

5-Hydroxyindoleacetic acid (5-HIAA)

 

5-Hydroxytryptamine (5-HT)

 

Histamine- same from mast cells

 

Insulin

 

Kallikrein

 

Motilin

 

Neuron-specific enolase (NSE)

 

A-Neuropeptide

 

K-Neuropeptide

 

Neurotensin

 

Pancreastatin

 

Pancreatic polypeptide

 

Platelet-dermal growth factor (PDGF)

 

Prostaglandins - same from mast cells

 

Pyroglutamyl-glutamyl-prolinamide

 

Secretin

 

Serotonin - is off the scale on testing for metabolite

 

Somatostatin

 

Substance P - pain chemical ( cna lead to fibromaylgia misdiagonis

 

Somatotropin release-inhibiting factor (SRIF)

 

Tachykinins

 

β-transforming growth factor (β-TGF)

 

Vasoactive intestinal polypeptide (VIP)

 

In the stomach entrocromaffin type cells are increased

Consumption of foods that contain serotonin can complicate the biochemical diagnosis of malignant carcinoid syndrome; in fact, the following foods contain an amount of serotonin that can produce abnormally elevated excretion of urinary 5-HIAA after ingestion:

 

Spinach

 

Eggplant

 

Cheese (eg, parmesan, Roquefort)

 

Wine (chianti, burgundy)

 

Caffeine

 

Tomatoes

 

Kiwi fruit

 

Bananas

 

Walnuts

 

Pineapples

 

Red plums

 

Avocados

 

The following drugs may have the same effects:

 

Isoniazid

 

Phenothiazine

 

Phenacetin

 

Monoamine oxidase inhibitors

 

Acetaminophen

 

Fluorouracil

 

Iodine solutions

 

If dietary (or pharmaceutical) 5-hydroxyindoles are excluded, a urinary excretion of 5-HIAA of 25 mg/d is diagnostic of carcinoid. If the range value is 9-25 mg/d, the differential diagnosis includes carcinoid syndrome.

Adapted from medscape -carciniod syndrome

Link to medscape info - http://emedicine.medscape.com/article/364581-overview#a19

Diagram above - Shows entrocromamaffin cells -The cells that grow too many and ina chaotic manner in carciniod .This happns slowly over many years .Many are found by chance . So becuase there are more cells than there should be the levels of chemicals relased are higher than normal - Many are the same as are relased from mast cells .This is why testing is needed to tell them apart .

Testing Tips ;-

S0 -high caelclamines but NO pheo -what could this be ?

- Hyperandergenic POTs

-which is seen with Etherlos danlos syndrome

 

-Histamine from mast cells and basophils cna cause the high levels as the stimaualte the adrenals to do this and low BP staimaualtes more norepinpeherine relase from nerves in our response to low circulating volume .

 

These links will take you to sources of information and help

 

Monoclonal mast cell activation syndrome

 

If BMB shows some criteria but not enough to be systemic mastocytosis then a new diagnosis ( 2012 ) will be applied . This is known as monoclonal mast cell activation syndrome . This is defined as one major crtiria but no minor - or 1 or 2 minor criteria . Click here for full detailed info

 

In wholly normal bone marrow biospy ( BMB ) - The search will move to

 

Mast cell activation syndrome (MCAS )

 

The criteria of tyrptase level for diagnosis has been defined - two samples - One on a normal day or 24 hours after all symptoms have resolved - and one in -ideally the first 2 hours of symptoms - due to tryptase being broken down from the 2 1.2 hr mark (WAO 2012 UK anaphylaxis 2008 )  

 

This is set at 20% of baseline  + 2 n/ml .

This is from Castells et al 2012

 

In these guidelines they also sanction histamine and prostoglandin tests of 24 hour collections of urine .But no level was set as diagnosistic as histamine can come from other cells -basophils . Doctors vary in how much weight they place on these tests .  These may be normal on an averge day and only high in an event . So repeated testing is required to catch a high .

 

In the USA a high urine histamine is seen as indictative of mast cell activation as is prostoglandins. But prostoglnadins alone with no other rise is not conclusive  .In the UK , doctors look at the whole picture .

 

Here in the Uk currently- If you dont have mastocytosis you will be investigated for other possibilites for your symptoms .

At this point any anphylaxis -if not IGE - will remain idiopathic .

These include

Cautions with tests which are publicised but not of value or recognised - click here