you know how most people like to come up with a list of new year resolutions at the start of the year? i’m not one of them.
i remember for the year of 2013, my resolution goes like this:
change to live, and live to change
and then i realize this will be my motto for my entire life from then on, so there’s no need for a new year resolution this year.
but i definitely need to give myself a kick-start.
sometimes i do feel kind of bad when all i post about are short updates.
i feel my brain rotting away when i stop thinking, i think even a zombie won’t be interested in eating my brain right now.
i might have given myself too long of a break since christmas time.
it’s much easier to absorb information than to synthesize them into something more functional.
the truth is, i’ve been reading way too much for the past few months (and that’s all i did!).
you’d expect me to have a system to organize all the new knowledge i acquired after going to college where i spent more time reading scientific journals than actually writing my own report.
i know right..
everything in my mind is like an organized mess.
i think it’s time to put an end to it.
i sorted through the organized mess and made it into an organized entry. 😀
the subject i’ve been reading on is none other than the skin.
i’ve been trying to figure out if there are any ways that i can trace the observation back to its cause.
in engineering, it’s called the black box.
i know the output and the input, but i do not know the process and that’s what i’m trying to figure out.
i make observations of my skin and try to explain them based on the things that could have happened in the micro level.
all in all, this entry could well be another brain fart of mine because it’s all conjectures that my brain came up with based on scientific research.
i do think about all these when i’m bored.
what a geek. =_=
enough of my ramblings.
I’ve made many observations along my recovery (these are mostly symptoms after my 2nd flare). The following are just some of the things I observed that might be explained by my own hypothesis.
More sensitive to change of temperatures
When I went from a cool room to a warmer room together with my brother, I started perspiring almost immediately while my brother was still thawing from the coldness.
I tan easily these days
When I was younger I never used sunscreen but will not tan much even after exercising in the afternoon sun for 2 hours. What happened after TSW? 30 min in the evening sun is enough to give my skin a grayish/brownish cast.
I also scar more easily than before
Each and every scab that forms will definitely leave behind scars in the form of hyperpigmentation. This is definitely something new to me. As I kid I always get my skin broken, but I never recall scarring so easily.
Skin dries easily when I’m in an air-conditioned space
My skin feels alright in Singapore’s outdoor (60-80% humidity). My skin feels best when it perspires, but I don’t feel good when I feel beads of perspiration roll off my head. In air-conditioned places, I can feel my skin drying up. Especially places where the skin is naturally thinner (the back of my hands and neck). When I touch those places I can feel them getting rough.
Superficial wounds heal and leave behind grooves
I did scratch a little too much sometimes and the wound started bleeding. A week later after the scab fall off, I can see my skin depressed. Much like the pock marks on my forehead! When I was younger and had lots of wounds, they never leave behind a depression like that. THANKFULLY, over a course of weeks the cells underneath the scar slowly fill up and level itself out.
More obvious appearance of pockmarks on my face
I’ve always had them ever since the chicken pox virus colonized me decades ago, but the marks they left behind was never this obvious. It was only after TSW that I realize they are glaring back at me suddenly. Oh well, hello!
Larger pores on my face
“mirror mirror on the wall.. oh wait, what the heck are those!?” that was the first time I noticed visible pores on my cheeks. I would be lying if I said I’m not alarmed. I’ve never seen them before. Is this a sign of aging, or is this from the TSW, or from steroid overuse? But I’ve never used them on my cheeks!
Aged looking skin
By that I mean the overall appearance of thinner looking skin, as well as tiny (I mean really really tiny) wrinkles and folds. Is it simply a case of steroid atrophied skin, or aging skin?
Before I go on, I thought it’d be useful if I introduce some terms so that you won’t get confused.
It would be good to know that our skin looks like this.
In my opinion it’s much akin to a rainbow cake, all 7 layers of goodness.
5 layers in the epidermis + 1 dermis + 1 hypodermis.
the 7 layers in our skin.
There are three main layers: epidermis, dermis, and hypodermis (also called subcutaneous layer). I can never look at my own skin the same way because the diagram makes skin looks like a slab of pork. Hahaha! Good lord, and my father just came into my room and asked me if I’m looking at a slice of pork belly.
And I would like to zoom in onto the epidermis because most of the action occurs here.
(source:  http://cnx.org/content/m46060/latest/)
The epidermis consist of 5 layers, the 1st being the stratum corneum, which is filled with dead skin cells called corneocytes. In this layer, the skin cells are held together by cellular glue (corneodesmosome) as well as skin cement (intercellular lipids). They give our skin its structural integrity as it keeps the corneocytes in place and fills out the empty spaces so that our skin is able to protect us appropriately .
Living in the 3rd layer (stratum granulosum) are keratinocytes (fancy name for living skin cells) that contains lamellar granules (little brown dots in the diagram, lets think of them as fish oil capsules) and it is a secretory cell that produces a range of stuff, including lipids (cholesterol, fatty acids and ceramides) that will eventually fill out the gap between the corneocytes in the stratum corneum after the cells progress from 3rd layer to the 1st layer (getting closer and closer to heaven huh..). Don’t forget that the cells are constantly moving upwards as nature dictates (keratinocytes are made in the 5th level and slowly progress up the levels as it matures. it will become the corneocyte after losing some of its childishness.). When the time has come, the lamellar granules will release the lipids into the intercellular space (between the dead skin cells) to form a barrier against water loss. The lamella granule has done its part and dies a hero (ungrounded scenario as imagined by me, no one knows what happens to the granule after it secretes). It should be noted that our cells synthesize its own lipids from raw materials available in our body, that means my blood do not just ferry the digested fats to my epidermis. I wish I can simply increase the lipid content in my epidermis by eating a high fat diet.. I also wish that I can decide where do the fats get stored (FAT HOPE, pun intended).
Of the range of things that the lamellar granule secrete, I’ll just talk about the lipids as well as the structural proteins for now because it’ll be related to what I’ll write about later. If you want to read more, you can always visit the link at the end of the entry to check it out (but don’t blame me if it makes your eyes bleed or hurts your head). The proteins that hold dead skin cells together are called corneodesmosome and it is also secreted by the lamellar body. It determines corneocyte cohesion and is one of the factors that contribute to sound skin barrier function .
Residing in the 5th layer is the melanocyte. It’s the cell that produces melanin, a colour pigment that gives our skin colour. It is activated when DNA is damaged in the dermis. The damaged DNA calls out to the melanocyte and says “it’s getting a little too sunny in here!”, and it will then produce melanin, which is a dark pigment that absorbs the harmful UV rays.
Underneath the epidermis is the dermis, where the fibroblast cells reside and produce connective tissue such as collagen and other water absorbing materials to give our skin structure. Most of the stuff (nerve endings, blood vessels, sweat glands, muscles and hair follicle) are also embedded in this layer.
OK, now that i’m done introducing those fancy scientific words to you, i can move on to share with you my hypothesis.
While I’m not sure if the changes in my skin are related to my excessive steroid use and the TSW (because most of the signs can well be a sign of natural aging), I managed to find some data that suggest that topical steroids do change the skin in a way that may result in the above symptoms observed.
What happens to the skin when steroids are used in the long-term?
- Suppressed cell proliferation -> lesser skin cells being produced -> thinner epidermis 
- Decreased formation of lamella bodies -> lesser intercellular lipids and disturbed desquamation process -> imagine a brick wall will insufficient cement, and a wall that can’t maintain an optimal thickness -> compromised skin barrier [1,2,3]
- Suppressed fibroblast activity -> lesser collagen being produced -> thinner dermis 
Allow me to explain myself so that everything may make more sense to you.
It is apparent that thinned skin is of significance here, not just in terms of the appearance.
Our temperature receptors are embedded in the epidermis of our skin, pretty damn near to the environment that our skin is protecting us from. What happens when you use a thin paper cup to hold hot coffee as opposed to a thicker cup? You’ll be able to feel the heat of the content much quicker than when using a thicker cup, right? Same theory applies here. The thinner skin allows heat to pass through my skin much more easily and quickly. In a sense, I’m now more responsive to temperature change as showed by my body’s reaction to increased temperature (perspiring) when I compare myself against my brother whose body has yet to respond to the warmer surrounding yet.
There are a whole range of stuff underneath our skin. The melanocyte (cells that produces colour pigments in our skin) resides in the bottom layer of the epidermis. Again, it is no surprise that my thinner skin is now allowing more UV rays to penetrate me. For melanocytes to start working, it means that my DNA is already damaged from the UV. Sad but true, thinner skin = higher susceptibility to UV damage.
Another possible reason for the increased ease of getting tanned is the increase activity of melanocytes. However, it is a little farfetched for me to relate my little observations to the HPA-axis depressing effect of systemic absorption of topical steroids for now (as I do not observe any other symptoms of HPA axis depression). I still have plenty of reading up to do before I want to talk about that, but for now, I’m just saying it could be part of the reason.
I believe the thinner skin + reduced level of intercellular lipids can explain for the dryer skin. I remember distinctly my skin got drier and drier over the years of steroid usage. Steroids does more than just to thin our skin. It reduces the growth of cells that produces lipids that fill out the intercellular spaces. Have you ever see someone use a sieve to scoop water? HELL NO! Because it’s so porous! Our skin become like that sieve. Water flows out of us freely (I doubt the atmosphere can be more humid than inside our skin, the law of physics will dictate the movement of water from region of higher concentration to region of lower concentration). So that probably explained my case of drier skin. If water can flow out freely, irritants can also enter freely. A damaged armor can’t protect us that well. Ever heard of the term “water of life”? A lot of microscopic reactions can only take place in water. Without sufficient water activity in our skin, I can only imagine how many reactions are affected. Exfoliation of the skin is one of the process that is controlled by the water content of our skin (because enzymes can only work optimally in a certain set of physical conditions), when desquamation is out of balance, it can either leave me with over thin skin that dries even easier, or thick scales that cracks easily. Either way it doesn’t sound pleasant to me.
The last 3 symptoms (depressed skin, pock marks and larger pores) could be due to the lower collagen production in my body right now. The fibroblast cells (collagen factory) which resides in the dermis takes a beating when topical steroids are used for an extensive time. Collagen is a type of protein that makes up most of the bulk in the dermis and it is what makes our skin plump and supple. From the larger pores and the increased visibility of my pock marks, I suspect that my collagen production has decreased dramatically. What used to fill out my skin and make the pock marks plump is now missing, I’m like a semi deflated balloon (with saggy skin T.T) right now. The thing about collagen production is that it will naturally decrease with time as we age, hence, I can’t tell if it’s just aging or the coupled action of aging PLUS steroid damage. For all I know, my mother’s skin is more plump than mine and she’s well in her 50s, I have reasons to believe it is mostly due to the damaging effects of steroids even though I did not use steroids on my entire face. Research has found that sufficient absorption of steroids can affect distal sites as well .
Initially I attributed the enlarged pores to dehydrated skin. But later on I realize it seems to be more than that. Well hydrated skin should be plump so that the appearance of pores will be minimized. No matter how I try to hydrate my skin, effects don’t last. Why so? Perhaps there is not enough humectants (humectant acts like a sponge) in my dermis to hold on to moisture? This points back to the lower levels of collagens, since they act as humectants in the dermis. Lower levels of collagen = lesser magnets to hold on to water = skin is less plump = appearance of pores.
The fact that my wound did level out eventually points to a slower collagen synthesis. Well, at least there’s still collagen being formed! I will be very sad if those wounds never heal totally, because that will mean that the steroids have dealt irreversible damage to my fibroblast cells (if you forgot what it is, the fibroblast is the mother of collagen).
The combined effect of thinner skin, decreased collagen and lipids give rise to the overall aged looking skin. Ok, I might be exaggerating when I said “aged looking skin”, obviously my skin do not look like it’s 70 years old, just that when I compare it with my friends of my age, it is evident that my skin looks slightly weaker than theirs.
All these are just the physical manifestation (that is observable by me) of the microscopic changes in our skin (that my naked eye can’t see). There is no way for me to actually find out what exactly is happening to my skin, I can only draw conclusions from observations and try to work my way back. I would like to repeat myself once again that these are just my personal thoughts of the cause and effects. Only God knows what exactly is happening to my skin (and the universe). One thing I know for sure is that my skin barrier is still subpar when compared to a healthy individual. The skin barrier is indeed damaged by the years of steroid use.
The next thing I would like to know is how I can normalize my skin faster, if there is a way at all. Several questions I have in mind pertain to the reversibility of cell damage. I think this is a question that most want to know. Now that I know what are some of the cells being affected by steroid usage, it makes it easier to search for possible targeted solutions. Even though some researched has shown that the skin thickens after 2 weeks of steroid cessation, the trials were run for a much shorter period of time as compared to many of our steroid usage duration, so it’s hard for me to extrapolate.
If it will take a very long time for my skin to recalibrate itself, I want to make sure I supplement my skin with stuff that can improve skin barrier function so as to ward off irritations. If I can stimulate normalization in any way, I would love to try it.
Till then, I guess I’ll have to leave it to my body. The body is such a wonderful piece of machine that nature has created, dissecting it and trying to figure out the individual mechanism appears to be futile because there is simply too many things going on at the same time, and they are all so precise and intricate. It hurts my head to think about all the possible reasons that might explain for the observations I made, as such I can only present several ideas that seems to be logical enough to be shared with you all.
Further reading if you’re interested. I’ve summarized some of the results from the journals which I have made reference to.
1. ADVERSE EFFECTS OF TOPICAL GLUCOCORTICOSTEROIDS
Ulrich R. Hennge, MD, Thomas Ruzicka, MD, Robert A. Schwartz, MD, and Michale J. Cork, MD
American Academy of Dermatology 2006
“Topical steroids have been showed to cause skin atrophy, which is denoted by the increased transparency and shininess of the skin. The action of topical steroids suppresses cell proliferation and also the inhibition of collagen synthesis. The dermal atrophy is probably caused by decreased fibroblast growth and reduced synthesis of collagen and acid mucopolysaccharides.”
On epidermal barrier disturbance:
“the decreased formation of lipid lamella bodies and delayed barrier recovery as observed by increased transepidermal water loss) was observed upon topical corticosteroid application. This effect may theoretically worsen barrier impairment…”
2. Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids
H.-M. SHEU1, J.Y.-Y. LEE1, C.-Y. CHAI2, K.-W. KUO3
British Journal of Dermatology, 2008
Long story short:
1. Topical steroid treated atrophic skin has fewer layers of horny cells as compare to normal control skin -> thinner skin
2. Lipid content of the stratum corneum was significantly lower than normal skin.
3. Marked decrease in numbers of intercellular lipid lamella of stratum corneum AND membrane-coating granules of stratum granulosm.
The membrane-coating granules they were talking about are most likely the lamellar bodies. The decrease in number of lamellar granules = lesser intercellular lipid lamellar in the stratum corneum = lower lipid content = higher water loss increased susceptibility to irritation/ decreased skin barrier function = increased skin irritation and dryer skin
3. Short-Term Glucocorticoid Treatment Compromises Both Permeability Barrier Homeostasis and Stratum Corneum Integrity: Inhibition of Epidermal Lipid Synthesis Accounts for Functional Abnormalities
Journal of Investigative Dermatology
Researchers investigated the effects of short-term (3 days) of glucocorticoid treatment (with a poten steroid, clobetasol).
- Delayed barrier recovery and abnormal stratum corneum integrity as observed by rate of barrier disruption with tape stripping. Topical steroid induced delay in barrier recovery was dose and duration dependent. Sufficient absorption can produce systemic effects at distal sites (places that was not in contact with steroids directly).
- Decreased stratum corneum cohesion as observed by the amount of proteins removed per stripping).
- Production and secretion of lamellar bodies were decreased, resulting in decreased extracellular lamellar bilayers. Also, the increase of lamellar body production that normally occurs after acute barrier disruption was inhibited.
- Global inhibition of lipid synthesis. Lipids required for lamellar body formation are synthesized locally within the epidermis. It was found that synthesis was inhibited by topical steroids by more than 50%. In addition, the inhibition of lipid synthesis is more apparently following acute barrier disruption (80%).
- Decreased density of corneodesmosomes in the lower stratum corneum. By replacing the lipids on the skin after tape stripping (free fatty acids, cholesterol and ceramides), stratum corneum integrity was corrected. Barrier recovery was also accelerated. It took more than a single application for the skin barrier to normalize. However, stratum corneum cohesion did not normalize.
Point 2 suggests changes to the intercellular glue (corneodesmosomes). It could be due to either a fall in the protease inhibitor or an increase in protease production, both the protease and protease inhibitor are secreted by the lamellar body.
Point 3 also means a defect in skin barrier function.
Regarding point 5, the statum corneum cohesion depends on the corneodesmosome and lipids in the epidermis. Clearly, it requires more than just the lipids to improve cell cohesion. The lamellar body that is responsible for the secretion of corneodesmosin has to function normally before cell cohesion can improve.
4 The mechanism of glucocorticoid effect in fibroblast
William B. Pratt, M.D.
The Journal of Investigative Dermatology 1978
1. Glucocorticoid steroids inhibit fibroblast growth and production of specific cell products such as collagen and mucopolysaccharide.
1. Too much sleep inducing mechanism was discussed in the paper which I have yet to digest. The results should be sufficient for now.
5. Lamellar bodies of human epidermis
Anne –Aurelie Raymond, anne Gonzalez de Peredo, Alexandre Stella, Akemi Ishida-Yamamoto, David Bouys, Guy Serre, Bernard Monsarrat, Michel Simon
Molecular & cellular proteomics 2008
6. Derived Copy of Anatomy & Physiology: A&P 1
Layers of the skin