Pique the Geek 20120527: Anaphylaxis

Anaphylaxis, also called anaphylactic shock, is a potentially life threatening condition.  I write about it tonight because yesterday afternoon my friend’s mum called me to come next door to see what was wrong with her.

When I got there she was having extreme difficulty breathing, had broken out in hives, and had swollen lips.  She was crying because of fear (EVERYONE panics when they can not breathe) and the pain from the rash.

I knew immediately that she was in trouble.  I told her mum to call the paramedics and asked if she had any diphenhydramine (trade name Benedryl).  She did not.

I went back to my house and found some, and I thought that I had used all of mine.  As if by Providence I did have one blister sheet left.  I took it to her and gave her 50 mg as soon as I could.  About 20 minutes later the paramedics arrived and started checking her.  I told them that I had given her the drug, and one of them said, “Well, that is what we would have done, except we might have given her epinephrine as well.”  I explained that we did not have any available that that was the best that we could do at the time.  He told us that I did the right thing, and her airway was already opening and the rash was resolving.  Her lips had gone back to near normal as well.

Her chest sounded OK to them and her blood pressure was normal for a 19 year old.  They told her that she did not need to go to the Emergency Department because of the diphenhydramine, but to call again if she got worse.  We all thanked them and they left.  Everyone thanked me for coming through with the proper treatment, and I just spoke with he a few minutes ago.  She has her voice back, although she still has a little chest tightness.  That is not surprising since she has asthma.

I found it interesting that her mum called me before she called the paramedics.  Over the course of time they have learnt to trust my judgment is such matters.  It made me feel good to be the resource of first choice to help my friend.

Now that the personal story is told, let us look at this very common and life threatening syndrome.  It is not a single malady, but rather a constellation of symptoms, some of which may or may not present.  It is the most severe allergic reaction known.

To understand anaphylaxis we first must become familiar with a couple of cell types and some chemical signaling agents that they carry.  The two most important cell types are basophils and mast cells.  Those are important because they contain large granules which contain chemical signaling agents important for allergic reactions.

The most important chemical signaling agents are histamine and several prostaglandins.  In anaphylaxis, histamine release is the most important cause.  Histamine is well known as the cause of allergic rhinitis (runny nose) and watery eyes from seasonal allergies (“hay fever“).  In these cases, the histamine release is relatively small but prolonged.

Histamine actually gets a bad rap because it is necessary for our immune systems to function properly.  It is only when histamine release gets out of control that bad things happen.  Here is the structural formula for histamine:

It is rather small molecule as far as biological systems go, but quite important.  It is a neurotransmitter, working with melotonin to control the sleep/wake cycle.  The presence of histamine tends to produce wakefulness, and that is why the first generation antihistamine drugs, like diphenhydramine, tend to cause drowsyness.  They cross the blood/brain barrier and occupy the receptor in an antagonistic manner to prevent histamine from doing its job.

This is primarily because those older antihistamatic drugs occupy the H₁ receptor and that is the one that has to do with sleep.  The new generation antihistamines are relatively nonsedating because they do not cross the blood/brain barrier much and so can not bind to that receptor in the brain.

These same receptors outside the central nervous system are also responsible for allergic reactions, one of those being anaphylaxis.  There are two ways that large amounts of histamine and other chemical signaling agents can be released.  One is through the immune system, whilst the other does not involve the immune system.

For the first type, immunogloblulin E (IgE) latches to some antigen to which the IgE recognizes as a foreign and unwelcome invader.  This is normal for attacking germs and is an essential part of the human immune response.  The activated complex then triggers mast cells and basophils to degranulate (release histamine and other chemical signaling agents, named because they are contained in granules in those cells) to attract white blood cells to attack the invaders, also an essential part of the immune response.

In anaphylaxis, this system goes into warp drive, and often substances other than harmful invaders trigger the response.  At high levels, those signaling agents, in particular histamine, cause the symptoms of hay fever if the immune system (where only slightly higher than normal levels are released) is only slightly hypersensitive to full anaphylaxis when very high levels are released.

The other way to cause these cells to degranulate is by direct interaction by either physical or chemical means.  I have experience with this because years ago the former Mrs. Translator had taken a bad fall and hit the back of her head.  She was having headaches and went to a neurologist to be checked.  As soon as they injected the X-ray contrast dye she went into anaphylaxis and almost died.  After in injection of epinephrine and IV diphenhydramine she got OK.  The very same thing happened to our neighbor’s sister and she almost died.  It turns out that contrast media cause this reaction quite often and clinics are now on the lookout for it.

Temperature extremes and mechanical shock can also trigger these reactions, and so can opiate drugs.  I have a theory that Janis Joplin may not have died from a herion overdose but rather from anaphylaxis induced by the heroin (or some other substance in it).  As I recall, her death was atypical for heroin overdose and that there was froth in and around her mouth.  More about that later.

One of the effects of high levels of histamine is bronchoconstriction along with smooth muscle contraction in the lungs and trachea.  Hives are also produced in many cases.  In addition, the H₁ receptor and the H₂ receptors cause vasodilation, making the capillaries leak fluid.  The combination of smooth muscle contraction and vasodilation conspire to close the airway because of swelling (from the vasodilation) and tightening of the muscles.

Think of it this way.  Imagine that the trachea is surrounded by a balloon with a little water in it, representing the smooth muscle.  The vasodilation causes the balloon to take on extra water, causing it to expand while at the same time the smooth muscle contraction make the balloon harder.  It it takes on enough water, the trachea is squeezed shut.  At the same time, the vasodilation causes the lungs to tend to fill with fluid, a possible explanation for the froth in and around the mouth of the late Ms. Joplin.

Another effect of the vasodilation is often a dramatic and life threatening drop in blood pressure.  Since the GI tract is rich with smooth muscle, nausea, vomiting,and cramps are not unusual.

My friend had many of the classic symptoms.  Her lips were swollen because of the vasodilation, her trachea was nearly blocked because of the combination of the vasodilation and smooth muscle contraction, and she had hives.  Although I did not let on at the time because I had to take charge, I was terrified.  I knew that there might just be a few minutes that could make the difference whether I would see my friend again.  Whilst I was at my house to get more diphenhydramine for her for later (anaphylaxis often returns) the paramedics told her that I most probably had saved her life by giving her it.

She was going to go to the clinic today because she still had a little throat tightness and hives, but was very much better than yesterday afternoon.  I called her and told her that she should ask about getting an epinephrine self injector (one brand is the EpiPen) to keep on hand, and always to have diphenhydramine close at hand.

Epinephrine is specific for anaphylaxis because it is a potent vasoconstrictor, thus reversing the vasodilation caused by histamine.  This rapidly opens the airway by taking water out of the balloon to use our previous analogy.  However, it is rapidly metabolized in the body and may have to be given repeatedly.  This is particularly probable in anaphylaxis caused by food allergies because the causative agent is continuously triggering the reaction until it is either digested or eliminated.  For single, short term exposure to an allergen (for example, a bee sting for sensitive individuals), a single injection is often adequate.  Here is the structure of epinephrine:

Interestingly, bee venom actually contains histamine, but not enough to cause anaphylaxis.  It does cause pain at the sting site, though.  Bee venom anaphylaxis is an immune system modulated reaction.

The second line of treatment (and the first one for us yesterday) are antihistamines, and diphenhydramine is usually the drug of choice.  It is a potent inverse agonist of the H₁ receptor.  Although it does not work as fast as epinephrine, it has a longer half life in the body.  It is a very old drug (FDA approved it for allergies in 1946), is well tolerated by almost anyone, and has an extremely wide separation betwixt therapeutic and toxic doses.  Here is its structure:

Whilst treatment is often effective, sometimes it comes too late.  People with known sensitivities to drugs, foods, stings, and so forth should keep a self injector and diphenhydramine with them at all times.  For drug (and latex) triggers, a bracelet is a good idea.  The bracelet is a form of prevention, and prevention of life threatening conditions is always preferable to treatment.

People with food allergies are at high risk.  I went to graduate school with a guy who had extreme reactions to peanuts.  Whilst he was there for his campus visit before he enrolled, the welcoming committee took him to one of the local Mexican restaurants.  Doug almost died.  Unknown to anyone but the kitchen staff, they used peanut butter in the enchilada sauce.  After a long time in hospital, he got OK.

If you look on food packaging you will often see a statement like “this product was produced with equipment that also processes peanuts” or some such.  You may also see words like “this product contains soy”.  These warnings are for those who have severe food allergies, but at restaurants the only thing that can be done is ask.  Do not assume that the wait staff know; ask the kitchen staff.

It is possible to desensitize sufferers from specific triggers by giving them repeated, small doses of the trigger to get the immune system accustomed to the trigger.  However, it is also possible for this treatment to provoke an attack.

My friend’s anaphylaxis is of the idiopathic kind, meaning that a definite cause is not known.  Unfortunately, up to 50% of cases are like hers.  We have some suspicions but nothing really concrete.  I hope that we can figure out what triggered her paroxysm, but the fact is that we may never know.

The bottom line is that anaphylaxis is life threatening and all too common.  I have personally know four people who had such a reaction, and two of them were and are very dear to me.  Somewhere betwixt 500 and 1000 people die from in in the US every year, and the lifetime risk for having such a reaction is betwixt one half and 2%.  That means that up to one person in 50 may have such a reaction sometime during their life.

This is NOT medical advice, but IS what I would do if my throat started to tighten and I was breaking out.  I would take 50 mg of diphenhydramine immediately and call the paramedics.  If I knew that I had a specific trigger, I would keep a self injector with me at all times.  By the way, those need to be replaced rather frequently because epinephrine is not particularly stable in aqueous.  I would also wear a bracelet if I knew that drugs or latex triggered it in me.

This story has a happy ending.  My friend is alive and well (well, much better) today.  I know that I will be able to see her tomorrow, and I am happy.  I have a real sense of making a contribution that may be what kept her alive yesterday, and I am glad of that.  Her little girl still has her mommy, too!  I had better stop before I get too emotional.

Before I close, I would like to take the opportunity to thank those who serve and have served in our armed forces.  Having worked as a civilian for the Army, I have many personal friends who were and are serving.  It is something that I would have found difficult to do because of my temperament, and I respect those who can.  In particular, I honor those who were killed or wounded in my defense.

Well, you have done it again!  You have wasted many more einsteins of perfectly good photons in reading this shocking piece.  And even though Donald Trump realizes that he is merely an impish clown when he reads me say it, I always learn much more than I could possibly hope to teach by writing this series, so please keep those comments, questions, corrections, and other feedback coming!  Tips and recs are also always welcome.  I shall stay around tonight as long as comments warrant for Comment Time and shall return tomorrow around 9:00 PM Eastern for Review Time.

I promised to give periodic updates about my experience with melatonin (link above).  It really puts me to sleep, but too often I fight it because I like to write in the wee hours.  One side effect that is quite welcome is that my lower digestive system problem has just about resolved, and it is not possible to express how nice it is to be able to eat a meal and not have immediately to go to the bathroom!  Melatonin will be part of my life for a long, long time.

Now I have about 80% of function back in my right hand.  I am typing with all ten fingers now, except for the bad habits that I acquired whilst it was weak.  I wear the splint only in bed, when typing, and when eating now.  I can type for a little while without it, but the muscles are still weak from disuse.  I am doing some weight therapy on it now to improve the muscle tone.

Warmest regards,

Doc, aka Dr. David W. Smith

Crossposted at

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