(Ironically Inflammatory) Acne and Fun-for-Me-to-Understand Tazarotene

So I’ve returned, after having retreated from the gay blogosphere for a month. Considerably too sober at present to blog for my merry audience, I’ve nonetheless decided to inflict myself on you. I’m very glad to be back.

I am so divested of mischief and spice this afternoon that I will refrain—even without reluctance—from blogging on certain illuminating, if not always decorous, and recent episodes in my life—like the one in which I unwisely helped myself to a great frosty pitcher of sangria in a crowded bar and promptly whirled on my sister’s boyfriend, who had also liberally helped himself, to yell an angry announcement of notions about his character that I had silently harbored in my breast for !!!!1111!!!!months!11!!!!!11!—but by now you must have guessed that my social skills are a wee rusty. (And that cats, detecting my outrageous old-maidishness, take to me easily.) So I don’t have to blog about it. Isn’t perceptiveness a very jewel of virtues? Especially in a blog readership!

Additionally, I’m gonna postpone blogging about inflammatory topics, like horny professors, or black people who hate my parents for marrying outside of their “races” or high fructose corn syrup. Which leaves me with the most sexless and yet relaxing blog topic of all: acne.
Read more. . .

My new dermatologist tells me he is willing to keep prescribing topical tazarotene to me. However, he warns me that an indefinite period of topical tazarotene use may increase my susceptibility to osteoporosis. (Emphasis his.) No, you don’t understand. Topical tazarotene is a wonder drug. Tazarotene ended a struggle with bad acne that lasted from age nine to age twenty-three. Tazarotene allowed me not only to look antagonists in the eye, but to hold my chin up while staring them down as well. Tazarotene finally effected the result that my fair-skinned classmates managed to achieve with OTC benzoyl peroxide, a therapy that made no difference on me. Tazarotene fucking erased what, to this princess, felt at once like a noble test of character and a veritable mask of bumps, crusts and gross, petty shame that hopelessly diminished my attractiveness to my peers as much as my dark skin and low voice and working-middle-class background did. Silly as it sounds, the first step I took away from (what felt like) a cabal of rich white males incapable of admiring any female who didn’t resemble The Last Unicorn in her heartached anthropomorphosis was a trip to the Very Famous Dermatologist who prescribed tazarotene to me—with assurances that I could use it indefinitely and that she had patients who did. What the hell, New Dermatologist? I’ve used this stuff for five years, and nary a mention of osteoporosis till you!



(Illustration of an ideal no amount of acne medication will help me meet. "Do I want to meet it?!" you gasp. Hell to the no. Of course not. I merely posted it here to acknowledge a ghost from my past. I warned you that I'm in a somber mood. h/t Dr. Isis for inspiring us all to make use of strategically-placed images in blog posts.)

However, this is not a post in which I wish to discuss my identity and self-image per se. That counts as an inflammatory topic, and I don't feel up to defending myself from attacks on my views today. Suffice it to say that I'm averse to discontinuing the use of my acne medication; my reasons have fluctuating degrees of superficiality.

What if New Dermatologist means the “irreversible osteoporosis” described in this FDA review, though? I am lately trying to take better care of my health anyway, since I know refusing to exercise and subsisting on coffee and high fructose corn syrup (drat!) isn’t as inconsequential to my energy level as it once was. And I already don’t get enough calcium as it is. So. Time to determine how comfortable I am with my current plan of !!!111nevah!!!111!! quitting tazarotene.

I'm not satisfied with asking some authority like New Dermatologist or Very Famous Dermatologist whether or not there's a grave probability that I'll hurt myself if I use this drug forever and leaving it at their answers. I want to understand what's going on. Why? Because I want to know. What will happen if I try to learn on my own?

The article linked above is about oral tazarotene (for psoriasis treatment). How much topical tazarotene must one absorb into the bloodstream to incur osteological damage? How much tazarotene have my bones been exposed to at present? If a patient is absorbing tazarotene through the skin in miniscule amounts, does that give her bones time to recover whatever density they may have lost as a result between exposures—unlike scenarios in which she directly ingests tazarotene? Can I offset damage with calcium supplements? Am I even asking these questions right? How do untrained patients learn to ask the right questions?

A Google search reveals nothing explicitly about the bone density of healthy acne patients and topical tazarotene. How well will I do at patching answers together from multiple studies? For example, this study in the Indian Journal of Dermatology, Venereology and Leprology finds that topical tazarotene is absorbed into the bloodstream at "less than 6%" and that it doesn't accrue in the body. It concludes that tazarotene is "safe". But, again, how much tazarotene would I have to absorb into my bloodstream to make it "unsafe"?

I can search PubMed, too, check if the researchers of interest have affiliations with Allergan, and read the titles of articles and conclusions of abstracts to get answers. “Is long-term use of tazarotene bad?” I want to know. No, says a reassuring German study. (This particular study mentions bacterial resistance in its abstract, but not osteoporosis.) PubMed searches of "osteoporosis + tazarotene" or "bone density + tazarotene" yield zero results. Obviously, "acne + tazarotene" generates plenty of papers to explore. Many of them are comparison studies, of tazarotene to another drug. One catches my eye: "The potential immunomodulatory effects of topical retinoids". How can topical tazarotene have any effect on your immune system if it metabolizes out of your body too quickly to gain a significant presence? Didn't the compromise of my mother's immune system during her chemotherapy for breast cancer last year lead to worries about her bone density? Am I simply misremembering something her doctors said? Would it be possible for an amateur to use a resource like PubMed to anticipate, from many different studies, side effects from long-term use of a drug that doesn't appear to be studied much in this capacity? How much science do I need before I get to start having ideas like that without being completely fucktarded? Am I being fucktarded now?

And what about the clinical pharmacology of tazarotene? Armed with online dictionaries, can I read and understand the insert that came with my prescription? (Available here.)

Tazarotene is a retinoid prodrug which is converted to its active form, the cognate carboxylic acid of tazarotene (AGN 190299), by rapid deesterification in animals and man.

My pitiful translation: Tazarotene is a vitamin A-like compound that only does what it’s supposed to do after your body’s metabolic processes convert it to its active form. Specifically, the active form is carboxylic acid and the metabolic processes are the quick dissipation of the volatile fruity odored product of the reaction between the carboxylic acid and the ethyl alcohol in the tazarotene compound. “Here, ‘cognate’ merely indicates that the carboxylic acid was derived from the vitamin A, right?” I think, already puzzled by my willingness to do this messy thinking in public. But it’s fun. Or soothing. “But how would a derivation of a compound react with the compound? Is it a chain reaction? Am I asking stupid questions again?"

AGN 190299 (“tazarotenic acid”) binds to all three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings is unknown.

My pitiful translation: This vitamin A-like compound binds to all cell surface molecules that recognize vitamin A acids. However, it favors one of this type of cell surface molecule, and this preference may modify gene expression. We don't know what this means in terms of side effects.

The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene’s therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and anti-inflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and cross-linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown.

Wait. What's a "rhino mouse"?

(h/t Ugly Overload)

WOW. Of course you are the darling of tazarotene studies. Not to mention dermatological researchers everywhere.

I had more. But I am presently bowled over, once again, by the power of genetic knowledge, and this will have to do it for today.