Transcript
Dr. Neal Bhatia (00:04):
Hi, I'm Dr. Neal Bhatia. I'm chief medical editor of Practical Dermatology. I'm here with the bestest of friends, Dr. Michelle Tarbox, chair at Texas Tech, good friend of Patrick Mahomes. And an understanding of urticaria. Let's talk about hives for a minute.
Dr. Michelle Tarbox (00:23):
I had a wonderful young lady that came to us for help. She had developed a very significant case of chronic spontaneous urticaria while she was undergoing fertility treatments, and it was very difficult to treat and was causing a lot of challenges for her in her day to day as chronic spontaneous urticaria often does. And it really inspired me to look into the question of could fertility treatments actually have an impact on the development of CSU? And to understand this question, you have to understand the impact that estrogen can have on the mast cell.
(00:52):
So in human beings, we have three estrogen receptors. We have an estrogen receptor alpha, estrogen receptor beta, and then there's also a G protein coupled estrogen receptor. And all three of those are actually on the mast cell. The way that fertility medications work is different class to class. So clomiphene is a selective estrogen receptor modulator and it works by inhibiting the signaling of estrogen at the hypothalamus. So it sort of lies to the brain and it tells the brain there's not enough estrogen. And so, that can trigger ovulation in patients who are having difficulty with that.
(01:23):
Now in that drug state, you either have normal or elevated estrogen levels. The other fertility treatments, the GNRH agonists, which work by actually binding to the GNRH receptor and stimulating it chronically when it's supposed to be stimulated in a pulsatile faction, will actually cause you to have a little flare up in hormone production and then it bottoms out. So almost no hormone production. That actually shows a protective effect against CSU. It sort of highlights the impact estrogen can have on this disease state.
(01:52):
Another medication that's used in fertility treatments is letrozole. That medication is able to actually interact in a way that doesn't really increase the production of estrogen. So the only one of the three classes that increases the production of estrogen potentially is clomiphene. So in the study that we did, we looked at the TriNetX database and we looked at patients who had exposure to fertility drugs and also a diagnosis of CSU subsequent to that. And we found an increased risk, about 33% statistically significant increased risk of CSU in patients who are on therapy with clomiphene specifically. A protective effect with the GNRH agonists, which makes sense because they bottom out hormone production. So you actually have lowered estrogen levels in that state. And then letrozole, the other treatment class, was a little bit kind of in the middle, but not really statistically significant.
Dr. Neal Bhatia (02:36):
Well, this is phenomenal. First of all, for boys, we forget about these drugs. And that's just shame on us. Second of all, do you remember the old days of progesterone dermatitis?
Dr. Michelle Tarbox (02:47):
Yes.
Dr. Neal Bhatia (02:48):
Is there maybe an overlap with the diagnosis and maybe something that we're not thinking about?
Dr. Michelle Tarbox (02:53):
You know, that's a really interesting question. And progesterone has a very interesting balancing effect on estrogen stimulatory response that it can have on mast cells. So in that setting, it's a little bit of a different scenario. There's almost like an auto allergy to progesterone and progesterone dermatitis, but both sets of patients can really significantly suffer and at the hands of the hormones that put us through all sorts of things as ladies. So I think it's a really important thing for us to be aware of as we're taking care of patients that have CSU, especially those who are in their childbearing years. And I think it also emphasizes that connection between estrogen and CSU as a disease state because we know that the disease state tends to peak in women in their reproductive years. It's very much connected.
Dr. Neal Bhatia (03:33):
I think that's actually something we don't talk about enough. And again, as a boy, I'm not going to go downtown with hormones, but at the same time, you and I can discuss the rationale for that. And I think this is very legitimate thinking about where do we go with the replacement, the discussion of their concomitant meds. And even more so in dermatology, we don't think about what else are you taking? When do you start hormone replacement and what are we doing about all of these impacts in urticaria? So I think this is actually really, really valuable. Last question is where do antihistamines, where do Bruton's tyrosine kinase inhibitors, where do they fit in this equation?
Dr. Michelle Tarbox (04:14):
This is a disease state that we have new guidelines on how to manage, which is wonderful. And we've added our new therapeutics to the sort of second step. So of course still, we're going to try to optimize the patient on up to four times daily dosing of oral antihistamines, but in those patients who are not adequately controlled on that dosing regimen, we have the option now to accelerate to any of the newer advanced therapeutics that are approved for CSU. And those of course include omalizumab still, alongside dupilumab and Bruton's tyrosine kinase inhibitors. For those patients who are going through fertility treatments because they're trying to conceive, the safest bet is going to be omalizumab because it has the most data, but there is a registry for dupilumab as well for both AD and CSU and it's shown a good safety signal. I think we'll be a little bit further down the road with BTK inhibitors before we get comfortable with that in pregnancy, but you raised a very interesting question earlier, which is what about hormone replacement therapy? And you've just inspired me to look into a new paper.
Dr. Neal Bhatia (05:09):
Yeah. There you go.
Dr. Michelle Tarbox (05:10):
This is what happens at Noah. Friends talk and get good ideas.
Dr. Neal Bhatia (05:12):
I was going to say, here's a surprise, Dr. Tarbox is going to make another paper. What a surprise.
