Hidden promotion for Benadryl (very clever).
Being diagnosed with hereditary angioedema is a nightmare. It’s itchy with successive attacks, painful and disturbingly swollen.
Today, I’m going to share a complete post about hereditary angioedema. You’ll discover the causes, the symptoms and available treatments.
This post is just for educational purposes. We’re not affiliated or endorsing any brands we mention in this post. And as usual, consult your doctor before taking any medication, as some drugs might not be suitable for you because each medicine has its side effects.
HAE is a familial disorder characterized by episodic attacks of severe swelling (angioedema). You can get it on your limbs, face, intestinal tract and airways.
Angioedema is pretty much like hives except that the swelling occurs in the deeper layers of the skin and for different reasons. Sometimes, you can get both the same time.
Milton (1876): First described clinical features.
Quinke (1882): “…Acute circumscribed edema of the skin…” (Sometimes, HAE is referred as to Quinke edema after him.)
Osler (1888): Angioneurotic edema (being related to the nervous system and was commonly called giant urticaria)
Donaldson and Evans (1963): Defined C1 – INH deficiency
Hereditary Angioedema Types:
There are three types of hereditary angioedema. The first type means you have low low C1 esterase inhibitor (C1-INH) levels in your blood. The second type means you have normal or elevated, but ineffective, C1-INH levels.
Type III is a new one; it was thought to be specific to women because a study has shown that 50% of oestrogen-exposed women with Type III HAE had decreased C1-INH inhibitory activity. C1-INH inhibitory activities had normalized when oestrogen exposure stopped.
I hope you’re not lost (yet). We’ll get to explain this C1-inhibitor better and simplify things, so just keep up with me.
It turned out that men can also have Type III hereditary angioedema because it is, in fact, a mutation.
In 2006, two different missense mutations in a non-conservative gene region were identified in German patients with normal C1-INH, located in exon 9 of the F12 gene. The point mutations were found in 5 unrelated families.
Therefore, these patients are classified as having HAE with a functional mutation in the factor 12 gene, abbreviated as HAE-FXII.
This gene (F12) helps in blood clotting (coagulation). F-XII is also an important stimulator of inflammation and is involved in the production of bradykinin and kallikrein (the villains). Remember these two, as from now on, things will make sense.
Now, let’s shed some light on our hero, C1-INH.
C1-inhibitor or C1 esterase inhibitor is an acute phase protein in your blood that helps in preventing inflammation.
C1-INH plays an essential role in regulating both the activation of the complement cascade and many of the serine proteases involved in the clotting and kinin formation processes.
So, what happens when you have low or malfunctioning C1-INH?
During acute attacks in patients with HAE, deficiency of C1-INH leads to the activation of serine proteases, which, in turn, increases the release of BK.
So, what are the possible treatments?
Ps: Anabolism=building, Catabolism=destruction, Metabolism=destructing to build
According to what we have, possible treatments include:
- Prophylaxis (prevention) by supplementing blood with C1-INH.
- Blockade of bradykinin receptors (the scientific fuss: KK inhibitor and a B2 receptor antagonist).
- Lowering kinin formation or helping kinin catabolism to prevent BK accumulation. This is very helpful for people with laryngeal (throat) attacks.
- Another way is helping enzymes to metabolize bradykenin.
There are plenty of solutions for hereditary angioedema, starting from the simple androgens (Danazol®).
Supplements of C1-INH include: CINRYZE® and Berinert®
Blockade of bradykinin receptors via icatibant injections, brand name: FIRAZYR®
The last two theories require drug companies to think of blockading both BK1R and BK2R, or of gC1q/p33, which I guess is not available for the moment.
I hope I didn’t cause you dizziness. Usually, I make my posts very simple.
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