Hives – A Body on High Alert

Today, we’ll be following an anaphylactic reaction to an allergen.  

Disclaimer: I’m not a doctor – just a bioengineer who happens to find pathophysiology fascinating.  If you find an error, please let me know!  Als0, NONE of my drawings are to scale.

An allergy starts out very innocently.  Everything is humming along: white blood cells patrolling the blood stream, stomach merrily digesting shellfish, or medicine destroying bacteria.

Meet Jill.


Jill’s taking a particular antibiotic for the first time, and it’s working great: fighting bacteria just like it’s supposed to.

Unfortunately, her white blood cells are getting curious.  One of them (a B-cell lymphocyte) just happens to have the perfect shape to fit onto a molecule of the antibiotic.

Hmm... what's this?
Hmm… what’s this?

This moment is where all the trouble starts.  While Jill finishes up her course of antibiotics, that B-cell is busy.  He thinks that the antibiotic is a foreign invader intent on destroying Jill!  He sounds the alarms by notifying his fellow-defenders, the T-cells, and begins to produce antibodies against the antibiotic.

Antibodies are small, Y-shaped proteins.  They bind to a specific region of an invader, like a bacterium, parasite, tumor cell, or allergen, very strongly – like a lock fits with one particular key.  Mostly, they float around in the blood stream watching for an invader.  When they find one, they surround it, and that alerts passing white blood cells to gobble it up.

Antibodies are on the lookout for particular invaders.
Antibodies are on the lookout for particular invaders.
Hives - Lassoing Leukocyte
Antibodies surround a bacterium, alerting a passing neutrophil. The neutrophil swallows and destroys the offender.

Some antibodies – like the one we’ll be discussing – prefer to be attached to cells (they’re called IgE antibodies).  So, the B-cell produces antibodies against our “evil” antibiotic.  These antibodies float around in the body until they find either a mast cell or a basophil, and then they stick to the cell membrane.  Basophils and mast cells are types of white blood cells.  They contain Jill’s only stores of histamine in small granules.  Basophils patrol the blood stream, but mast cells prefer a more settled life inside tissues like the skin.

Basophil in the bloodstream says hello to mast cell chilling in the skin.  "Nice accessories."  Antibodies adorn the cell membrane, and dark granules inside the cell store histamine.
Basophil in the bloodstream says hello to mast cell chilling in the skin. “Nice accessories.” Antibodies adorn the cell membrane, and dark granules inside the cell store histamine.

So, we are all set up for the big allergic reaction.  The antibodies are stuck to the basophils and mast cells, which are patrolling both the blood stream and the tissues.  Everyone is just waiting and watching, ready for the invader to return…

Then, Jill gets sick again.  Her doctor prescribes the same antibiotic, and she takes it.

Dunn dunn dunnnn.

Shortly after the medication hits Jill’s digestive system, it’s absorbed into the blood stream and sent through the whole body.  The antibiotic is hunting for bacteria to kill, but the antibodies are hunting for it!

The antibiotic flows past a mast cell, and the antibodies grab it out of the blood stream.  This binding alerts the mast cell that something bad is happening, and it responds by sending out all of its little granules full of histamine.

"Go! Go! Go!"
“Go! Go! Go!”

Histamine is responsible for all of Jill’s misery in the coming days.  The cells lining her blood vessels contain receptors for histamine.  When the cells recognize the histamine, they dilate the blood vessels, making her skin turn red.  They’ll also increase the permeability of the vessels: this mechanism is designed to let out white blood cells, the defenders, so that they can get to the site of the invasion.  The increased permeability will let out extra fluid as well, causing her skin to swell.  Finally, in a mechanism that is very poorly understood, histamine also causes extreme itchiness.  Thus: HIVES.

Hives on the arm, from Wikimedia Commons.

Fortunately for Jill, this could be the worst of it!  Most allergic reactions like this, though severe, won’t progress to anaphylactic shock.

I see, you’re a MythBusters fan.  You like to see things blow up at the end of the episode.  You want to see her go into shock.  You terrible, terrible person.

Let’s go.

The difference between anaphylactic shock and the anaphylactic reaction I just described, which basically only involved hives, is only a matter of degree.  If more histamine is released, or if Jill’s cells are more sensitive to it, bad things happen.

The permeability of blood vessels can happen in the lungs, too, instead of being limited to the skin.  This permeability causes swelling in Jill’s throat, making it hard to breathe.  If the swelling keeps going, Jill could die.

Or, she could die from a loss of blood volume.  Though Jill isn’t bleeding, she’s losing plasma throughout her body due to the leakiness of her blood vessels.  And, although localized dilation of blood vessels isn’t a problem, dilation all over is.  Essentially, Jill has dramatically increased the volume of her “pipes” without increasing the amount of fluid flowing through them.  That means that very little blood returns to the heart, so it has almost nothing to pump to vital organs like the brain.  Jill’s heart starts trying to pump faster and faster to make up for the lower volume being pumped each time, but it’s not enough.  Jill is dying.

“Wait, wait, wait,” you might be saying.  “Why is Jill’s body about to kill itself over a medicine?  Why does this system exist?”

To answer that question, we take a journey to the tropics.  Ahh, the sun is shining, the birds are singing, and the parasites are trying to invade.  It turns out that people in the tropics have a much higher concentration of IgE – the type of antibody that causes the allergic response – than people in the US.  Scientists think that the system is designed to recognize invading parasites and cause, essentially, localized hives.  As the parasites are trying to invade a person’s skin, they would be immediately greeted with a host of white blood cells (brought to the site by the leaky blood vessels).

"Hello, scoundrel."White blood cells greet a parasitic worm trying to invade the skin.
“Hello, scoundrel.”
White blood cells greet a parasitic worm trying to invade the skin.

Thankfully, those of us in the US and many other developed countries don’t have to deal with invading parasites.  But, that leaves our IgE system with nothing to do!  So, it looks and looks and looks for parasites, finds an antibiotic or a piece of shellfish, and says, “Eh, close enough.  ALARM! ALARM!”  Since the medication or food was in the blood stream, the localized response that was supposed to defend against a parasite happens all over your body, leading to large patches of hives or anaphylactic shock.

Okay, back to Jill, who, may I remind you, is dying.  Her friend Jack has recognized Jill’s distress and rushed her to the nearest ER.  The first thing they do is give Jill a shot of epinephrine (also known as adrenaline).  This molecule is designed to pump you up for fight or flight, and it does so by constricting your blood vessels, which gives your heart more blood to pump.  For Jill, it will help counteract the effects of histamine.  Her heart will receive more blood from her body, and it will be able to send the blood to Jill’s brain and other organs.  Doctors may also put a tube down her throat to help keep her airway open while the epinephrine does its job.

Whew, crisis averted.

After the initial crisis is over, Jill will be treated with anti-histamines.  Yes, your good old friend Benadryl.  Benadryl keeps histamine from binding to the cells lining blood vessels, preventing them from dilating and leaking.  She might also be given steroids, but their use is highly debated.  Some research claims that steroids do no good whatsoever; other research suggests that steroids can help keep the immune system from continuing to react against the allergen or help reduce the swelling that anaphylaxis caused.

Thankfully, in a few days Jill will be back to normal.  And she’ll never take that antibiotic again.




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