Thread by @MughalDerm

European Standard Battery numbers 27 and 28 as well as the steroid battery.

#dermtwitter #medtwitter #MedEd #contactdermatitis @ACDS_Dermatitis #RockyIV #steroids

This one will be about steroid allergy. Hold on to your hats, you will be entering the geek zone

I said GEEK not NERD. Amateurs.

Let's start with a question. A patient tests positive to Tixocortol-21-pivalate on patch testing. Which of the following steroids is most likely to cause an allergy also?

No need to show your working

The answer is C. Hydrocortisone 21 acetate.

Steroids are called steroids because of their common 4 ring structure. They share structures with cholesterol, bile and many other compounds. They provide a variety of functions but in dermatology, they are used for their immunosuppressive actions.

This means they reduce inflammation in autoinflammatory diseases (body gets inflamed by itself) and reduce immune function in autoimmune (body attacking itself) conditions.
We are talking about corticosteroids not anabolic steroids like the ones Ivan Drago took in Rocky IV

Corticosteroids are made by the adrenal cortex (outer part of the adrenal glands). These would break down muscles (catabolism) rather than build them up (anabolism).

Corticosteroid allergy is very difficult to get to grips with. If you have eczema or other inflammatory skin conditions, allergy to the steroid used to treat it could be a reason for treatment failure. This is not as common as nickel or perfume allergy but does happen.

Patch testing to steroids is hard. The steroids actually suppress their own allergic reaction so the allergy often looks like a ring. The middle having the higher concentration. Getting the test concentration right has taken a lot of time and effort.

In addition, steroids are modified as they enter the body. Tixocortol-21-pivalate has the 21 ester hydrolysed as does hydrocortisone-21-acetate. This makes them identical molecules as far as the body is concerned.

Now, if you are allergic to one steroid, you could be allergic to others. In the past, steroid allergy was divided based on chemical structure and similar ones were deemed to cross react with each other. This was the Coopman classification.

Then along came Baeck et all in 2011 in the journal Allergy and everything changed

It turned out, some people reacted more to the molecular charge of the molecule and others reacted more to the structure of the molecule, reflecting differing HLA types and reaction patterns. The patient AND the steroid mattered as to who would react where and how.

It turned out C16 methyl substituted steroids were most hypoallergenic. 3 clusters of steroids were identified. Cluster 1 had no C16 methylation. Cluster 2 had C16/17 ketal/diol.
Cluster 3 had C16 methylation and all had halogenation.

Ask @RoySocChem for details. The C number is the carbon atom that things are attached to. The suffix -ol refers to alcohol OH group. Methylation to a CH3 group attached and halogenation to fluorine or chlorine attached. Other halogens do not really occur here.

Some molecules were more closely related than others and the paper shows a dendogram (family tree sort of thing) of the steroids involved.

Some people reacted to all 3 clusters. Some to just one. Cluster 1 was the biggest group and overlapped almost entirely with cluster 2 but clusters 2 and 3 overlapped a lot less. There were very few that only reacted to cluster 2 or 3 but many that only reacted to cluster 1.

So what did this paper tell us?
Well, more so than anything, if you suspect steroid allergy, get a patch test. There is no point trying to work out what cluster you are in and as for the Coopman classification, forget it. That's the only way you are really going to know.

Also, if you suspect steroid allergy, a Day 4 reading is unlikely to be enough. Day 7 or repeated open application tests are likely needed for greater accuracy.

Are you still with me?

Let's end with a question. Which of the following topical steroids is least likely to cause a type IV hypersensitivity reaction?

Cluster 3 steroids are least allergenic but...

Keep it simple. Mometasone on that list is least likely to be allergenic to go for those if you are worried which to choose from.

I hope you enjoyed that tweetorial. As always thanks to @DrStevenTChen and @patchtestYu for the inspiration. Thanks to @Dolph_Lundgren for making his image awesome from Rocky IV. Looking good, Dolph.
And thank you for your attention