Feeling Ulcerative: Colonic Artwork

Inflammatory Bowel Disease. For those of us who live with it every day, it has a massive impact on who we are. It can reach deep into our soul (and gut!) and affects us both emotionally and mentally. Often times, these struggles can be challenging to convey to others.

Matthew Lee, an Ulcerative Colitis patient, portrays his life with UC through creative artwork. He has generously allowed us to share his colitis sketches below:

Thanks again to Matthew. We found his visual impressions of UC inspiring.

GUTS is always looking to share creative work by members of the autoimmune disease community. Feel free to contact the editor at heltzect@gmail.com if you would like to share your work on GUTS.

Inflammatory Bowel Disease: An Autoimmune Conundrum

Inflammatory Bowel Disease: An Autoimmune Conundrum
Assessing Traditional and Modern Treatment Paths, and How to Look Forward

by CT Heltzel

Introduction

In Western society, people’s immune systems are becoming increasingly unstable, and their guts more sensitive. A major contributor to this is the rising number of people in the world who suffer from Inflammatory Bowel Disease (IBD). An estimated 1-1.3 million people in the US live with IBD, with as many as 70,000 new cases every year. IBD refers to a group of several autoimmune conditions that affect the colon or entire gastrointestinal tract. The two major classifications of IBD are Crohn’s Disease (CD) and Ulcerative Colitis (UC). Physicians diagnose a comparatively small portion of IBD patients with various types of “indeterminate” colitis. Both CD and UC present similar symptoms resulting from an overactive immune response in the GI tract, and commonly require similar medications for treatment. However, significant differences exist between the conditions that both physicians and patients must take into account when deciding upon treatment. Expressed symptoms specific to UC and CD create a need for alterations and selectivity to the types of inflammation ameliorating drugs patients decide to use. Modern medical treatments of IBD vary widely in approach to relieving inflammatory symptoms. Many of these treatments successfully relieve patients of their symptoms, often to the point of total remission. Despite this, nearly 70% of CD patients and 35% of UC patients will require major surgery after diagnosis1. Further, the medications required to treat IBD often cause dangerous side effects.

People with the condition are often on long term regimens of steroids and immunosuppressive biologics. In accordance with this, medical costs skyrocket and biologics have shot up to the top of the drug market. This is indicative of the impact autoimmunity is having on the US population. Millions of people pay extreme amounts to manage symptoms, but are never truly healthy. IBD is an emergent disease that is increasingly more threatening to population health in the US and other highly developed nations by forcing large groups of people to live immunocompromised and chronically ill. Fully understanding the current state of IBD research and treatments requires thorough investigation of several key subjects. Immune pathways and pathogenesis of the disease, modern treatments, and current research should be analyzed.

Pathobiology and Immunological Mechanisms

Among the many issues associated with IBD diagnosis and treatment is the lack of a primary source of known pathogenesis. Like many autoimmune conditions, IBD is described as a multifactorial disease, having several potential contributing actors and no easily recognized, common origin. These factors are broadly categorized as genetic predisposition, environmental triggers, and immune system disruption. Population studies demonstrate many common characteristics between people who have IBD, but they are not consistent as people may have one or a combination of many of these factors while maintaining similar or differentially severe pathogenicity as other patients. Examples of these factors include intestinal microbiome compositions, genetic mutations, lifestyle choices like smoking, or disease triggered after infection or injury.

Patients with active IBD show greater infiltration and activation of innate (e.g., macrophages) and adaptive (i.e., B and T cells) immune cells in the intestinal mucosa. The intestinal mucosa consists of the top epithelial layer of cells, or intestinal epithelial cells (IEC), in the gastrointestinal tract. Hyperactivity of immune cells causes heightened production and recruitment of more inflammatory agents in the mucosa. Proteins that signal immune cells to react in various ways, referred to as cytokines, represent the most relevant agents causing inflammatory proliferation. Specific cytokines of interest include tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), and cytokines associated with the interleukin-23—Th17 pathway2. These cytokines and cytokine receptors associate with T-cells via secretion or expression on the cell membrane. IBD research and treatment focus primarily on modulation of CD4+ T-cells, or helper T-cells (Th). Cytokine receptors can bind to various biological subunits and activate the differentiation of naïve (unactivated) CD4+ T-cells into several sub-types of helper T-cells. Differentiation into specific Th cells depends n activation by respectively associated interleukins (IL), cytokines that foster growth and differentiation of T-cells. Dysregulation of CD4+ T-cell differentiation into Th1, Th2 and Th17 holds a heavy implication in the pathogenesis of IBD3. Current research and treatment focuses heavily on the function of these immune cells as a potential route for therapeutic target discovery.

Modern medical treatments for IBD vary widely in mechanisms of action and biological targets. In essence, certain medications perform more effectively for ther CD or UC and for different severities and locations of disease symptoms. 5-Aminosalicylates (5-ASA), for example, provide greater symptom amelioration for UC since the medication mostly effects the colon. 5-ASA binds and activates the anti-inflammatory receptor Peroxisome proliferator-activated receptor-γ (PPARγ) in colon-based IECs4. Figure 1 highlights the differences between the diseases relevant to treatment.

The main types of drugs used to reduce IBD symptoms in current treatments fall under a few specific categories. From least to most extreme, physicians and researchers commonly group treatments as 5-aminosalicylates (5-ASA), corticosteroids, immunomodulators, or biologics. Physicians regularly prescribe all of these medications, sometimes in a combination treatment including more than one. However, physicians must balance medication effectiveness with harmful side effects. The balance between the two fuels a controversial argument in the scientific community: which treatment path best leads to long-term remission with the lowest potential for negative side-effects? The treatment paths in question for IBD generally fall under two schemes known as “Step-up” and “Top-down”5.

The former represents the traditional approach in which treatment uses weaker medications followed by harsher medication in accordance with increasing symptom severity. Top-down involves first utilizing the most powerful immunosuppressive drugs, such as biologics and immunomodulators, to eliminate symptoms quickly. Subsequently, physicians treat with weaker medicines as the patient moves towards remission6. The top-down approach becomes increasingly popular as more patients see positive results from use of biologics. However, many physicians and scientists are not supportive of such an approach, seeing the dangers of immune system suppression as an unethical first-line of defense. The most common immunosuppressive biologics commercially available include anti-TNFα antibodies, such as infliximab (Remicade®) or adalimumab (Humira®). These antibodies locate and bind to the TNFα cytokine and inhibit its activity7. This approach provides effective amelioration of IBD symptoms since TNFα is greatly overexpressed. However, lowering function of this cytokine lowers overall immune function and T-cell development which can be unhealthy and leads to potential infections.

Biological Target and Drug Efficacy

The uncertainty towards a superior therapeutic treatment method within the scientific community suggests significant room for innovation in the realm of IBD medications. Deciding on what constitutes a high efficacy biological target forms the first major hurdle in the research process. Measurability of the target in question can make pursuing research either plausible or unlikely very early on. Time and expenses limit the necessary devices and techniques at a laboratory’s disposal to measure a potential target, as well as the feasibility of measuring it based on biological and chemical characteristics. Beyond financial and experimental obstacles, the most important criteria relate to biological function. Specificity of a target to the disease process probably counts as a main feature of significance towards efficacy. Preferably, the target is unique to the condition’s mode of action and has a potent effect on symptoms without unwanted inhibition of other physiological processes. A target proximal to symptom initiation holds a similar importance to specificity. Proximity refers to closeness to disease related symptom initiation. Affecting the target hopefully does not affect other, possibly unrelated, processes prior to symptom initiation in the inflammatory cascade. Another scenario for good proximity involves prevention of symptoms, rather than clearing the aftermath. For the purposes of IBD treatment, a target that has high systemic expression instead of local expression to one part of the GI tract can be of great interest to researchers. Some targets fail to be useful, as they do not have great presence in all possible areas of inflammation.

The types of compounds composing drugs used to treat inflammation are also relevant to the quality of a treatment. The difference between a small molecule and large molecule drug can make a great difference in the comfort of a patient. Currently, anti-TNF-α biologics represent the most potent drugs on the market. These antibody-based medications are large molecules and patients apply them via injection/infusion. Small molecule drugs commonly utilize oral delivery, a preferable method for most patients. For the sake of easy application to the patient, a small molecule with potent effects on inflammation makes for a desirable compound to research. Most importantly, a drug should have low toxicity. Additional short or long-term side effects from therapy essentially defeat the purpose of researching a new IBD drug. The negative side effects researchers observe in preclinical trials root out potential drugs early on.

Current IBD Treatments

As described previously, physicians prescribe several types of medications to treat IBD. Each classification differs greatly in biochemical mechanism and there are many drugs on the market within these classifications for physicians to utilize. A patient with severe IBD symptoms commonly begins treatment with corticosteroids. A typical beginning of treatment shared by many IBD patients involves use of the drug Prednisone. Corticosteroids such as Prednisone bind to glucocorticoid receptors and proceed to downregulate gene transcription for various inflammatory agents8. This corticosteroid has uses in many conditions outside IBD and thus has the negative attribute of many side effects unrelated to inflammatory relief. Physicians avoid use of prednisone and other steroids as a long-term solution. Once patients achieve short-term symptom relief by use of steroids, physicians attempt design a new treatment regimen for long-term stability.

Physicians commonly prescribe 5-ASA as a next step after steroids, or possibly before if symptoms start out mild. This progression falls in line with the top-down treatment path. As stated earlier, 5-ASA acts as a ligand, binding to PPARγ and activating its anti-inflammatory effects in IECs. 5-ASA drugs commonly prescribed by physicians include Asacol and Pentasa. These drugs act locally in the gut, which make them very effective for UC and mild-moderate cases of CD. The local predominance allows for minimal systemic side effects, leaving the most common ones related to digestive organs. Such side effects could include diarrhea, flatulence, or cramping. Despite minimal side effects, the inability of 5-ASA to cause potent anti-inflammatory effects outside colonic IECs makes these drugs ineffective in severe cases of CD. A preemptive colonoscopy allows physicians to find areas of inflammation local to the colon. Observing severe inflammation outside the colon may cause a physician to bypass 5-ASA treatment.

Chemical immunomodulators cause potent immunosuppressant effects to reduce inflammation, often in relief of or in conjunction with 5-ASA usage. Thiopurines such as mercaptopurine (6-MP) and azathioprine (AZA) act as small molecule immunomodulators that suppress the immune system much like biologics. They are used for more moderate IBD symptoms and have less potent effects9. 6-MP functions as a competitive antagonist of GTP, binding to a small GTPase protein, Rac1. Binding to Rac1 suppresses activation of the protein in gut CD4+ T-cells, and causes cell apoptosis10. This reduction of CD4+ T-cell activity creates significant anti-inflammatory effects throughout the GI tract. However, thiopurines have many faults outside of immunosuppression that make them ineffective as a final treatment for many patients. Not all sever cases of IBD appear to associate with Rac1 based T-cell proliferation, often causing patients to use biologics as a powerful alternative.

Physicians prescribe biologics such as Remicade (infliximab), Humira (adalimumab), and Cimzia (certolizumab) in cases of severe CD, often when all other medications fail to relieve symptoms. All the biologic medicines above consist of monoclonal antibodies that work as TNFα antagonists. The antibodies bind TNFα and inhibit its ability to signal, lowering development and recruitment of various inflammatory agents. With the FDA approval of Humira as a CD medication in 2007 and for UC in 2012, biologics will continue to rise to the top of the IBD drug market11. Negative side effects such as risk of infections due to high immunosuppression and the possibility of increased lymphoma occurrence (uncommon in short term use) present significant issues with anti-TNFα biologics12. Despite this, the usual high remission rates using these medications often outweigh any negatives for IBD patients. Non-TNF based biologics such as ustekinumab (Stelara) and vedolizumab (Entyvio) have hit the market in recent years, as well, and provide potential alternatives in the realm of powerful large molecule drugs. Stelara binds to the p-40 subunit shared by the IL-12 and IL-23 cytokines. This keeps p-40 from binding to these cytokines, making it unable to send a signal for T-cells to differentiate into inflammation promoting Th17 cells13. Entyvio blocks lymphocyte trafficking and adhesion in the gut through its recognition and blocking of the α4-β7 integrin glycoprotein on B and T-cells14. This does not appear to cause systemic immune suppression in the rest of the body, making the drug a potential safe alternative to anti-TNFα antibodies. Still, immunosuppression in general is an unhealthy practice, leaving significant room for innovation in future IBD treatments.

Because of the aforementioned success of biologics in diminishing the symptoms of people with IBD, as well as millions of others suffering from autoimmunity, these drugs are more and more likely to be prescribed and have risen to top grossing positions in the pharmaceutical market15. With this comes the implication that millions of people are also being critically immunocompromised over significant periods of time, causing dysregulation of the body’s innate bio-molecular mechanisms. Such blanket treatments could be viewed as unethical on that large of a scale without looking forward to new methods. But what could be done to better regulate this system of treatment? How can we better meet patient’s needs? One answer is using precision medicine as a path towards pinpointing disease pathogenesis on a person by person basis. The concept of precision medicine utilizes multiple avenues of modern clinical research tools to personalize the treatment path for patients. This method seeks to combine pharmaceuticals, nutraceuticals, bioinformatics/genomics, and microbiology to understand and approach the driving force behind a patient’s condition16. IBD is one of the most practical areas to start using precision medicine because of its multifactorial nature. Computational models of the intestinal immune response can be developed that use patient data on microbiome and immune cells and molecules as a baseline and are calibrated to an individual using their specific bacteria, mutations and disease pathology as input parameters. The outputs of such a model would inform clinicians on the best types and amounts of therapy needed to return someone to a healthy immunological baseline. In order to do this, however, massive epidemiological studies must continue to be conducted on willing patients through public health initiatives that involve numerous practitioners, hospitals, and testing sites. Using the collected data, researchers will be more capable of creating refined and accurate models of disease that can be turned into a reliable clinical tool17.  This data will also be critical in determining what initiatives must be put forward to focus on preventive measures. Big epidemiological data can lead to pathological origin trails that may inform what needs to be regulated or removed from typical human consumption. It is likely this will involve limitations on regulations on human exposures to antibiotics, food pesticides, preservatives, and other chemicals that we come into contact with on a daily basis that could be brought to light via connections made in the computational model of disease. If bioinformatics continues to progress as quickly as computational systems typically do in modern times, there may yet be hope for a world unburdened by chronic inflammatory bowel disease in the near future.

Autoimmune conditions like IBD remain difficult to control because of the high complexity of human immunity. Diagnosis rates for the condition grow yearly, and more individual must learn to manage crippling intestinal damage or depleted immune systems. Current medicines provide effectiveness relief for many patients, but have the potential to be much safer. For this reason, it is important that research on new therapeutic targets and treatment paths for IBD treatment continue to develop.

  1. Maggiori, L.; Panis, Y., Surgical management of IBD–from an open to a laparoscopic approach. Nature reviews. Gastroenterology & hepatology 2013, 10 (5), 297-306.
  2. Abraham, C.; Cho, J. H., Inflammatory Bowel Disease. New England Journal of Medicine 2009, 361 (21), 2066-2078.
  3. Abraham, C.; Medzhitov, R., Interactions Between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease. Gastroenterology 2011, 140 (6), 1729-1737.
  4. Iacucci, M.; de Silva, S.; Ghosh, S., Mesalazine in inflammatory bowel disease: a trendy topic once again? Canadian journal of gastroenterology = Journal canadien de gastroenterologie 2010, 24 (2), 127-33.
  5. Hanauer, S. B., Positioning biologic agents in the treatment of Crohn’s disease. Inflammatory bowel diseases 2009, 15 (10), 1570-82.
  6. Blonski, W.; Buchner, A. M.; Lichtenstein, G. R., Inflammatory bowel disease therapy: current state-of-the-art. Curr. Opin. Gastroenterol. 2011, 27 (4), 346-357.
  7. Pollack, P. F.; Hoffman, R. S.; Renz, C., Uses and compositions for treatment of Crohn’s desease. Google Patents: 2013.
  8. Emilie, D.; Etienne, S., [Glucocorticoids: mode of action and pharmacokinetics]. La Revue du praticien 1990, 40 (6), 511-7.
  9. Goracinova, K.; Glavas-Dodov, M.; Simonoska-Crcarevska, M.; Geskovski, N. In Drug targeting in IBD treatment-existing and new approaches, InTech: 2012; pp 301-332.
  10. Neurath, M., Thiopurines in IBD: What Is Their Mechanism of Action? Gastroenterology & hepatology 2010, 6 (7), 435.
  11. FDA FDA approves Humira to treat ulcerative colitis. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm321650.htm.
  12. Williams, C. J. M.; Peyrin-Biroulet, L.; Ford, A. C., Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-alpha therapy in inflammatory bowel disease. Aliment. Pharmacol. Ther. 2014, 39 (5), 447-458.
  13. Frleta, M.; Siebert, S.; McInnes, I. B., The Interleukin-17 Pathway in Psoriasis and Psoriatic Arthritis: Disease Pathogenesis and Possibilities of Treatment. Curr. Rheumatol. Rep. 2014, 16 (4), 8.
  14. Ghosh, N.; Chaki, R.; Mandal, S. C., Inhibition of Selective Adhesion Molecules in Treatment of Inflammatory Bowel Disease. Int. Rev. Immunol. 2012, 31 (5), 410-427.
  15. FDA FDA approves Humira to treat ulcerative colitis. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm321650.htm.
  16. NIH, All of Us Research Program. https://www.nih.gov/research-training/allofus-research-program
  17. MIEP, Computational Models. http://modelingimmunity.org/computational-models

A Colitis Warrior, Part I: Cherry Kool Aid

Hello, all! GUTS is back and running after a holiday break and we are continuing our contributor content with our first post from Reddit user /u/Hunhund. She is an Ulcerative Colitis patient who chooses to approach the condition with an awesome sense of humor that we think many of you will enjoy and relate to.

WARNING- The article below contains explicit language

Her story begins:

 

What a Shitty Disease!

 

Well, hello there! I’m going to tell you a little bit about myself and my weird “journey”, we’ll call it, over the last two years. I am an Ulcerative Colitis sufferer, warrior, woman with many talents and stories to tell. I hate saying “sufferer” because it implies defeat in my opinion, but it’s a label anyone afflicted with a chronic disease is given. Warrior is a term I love to use because we fight with our own bodies every single day, and my favourite martial art is humour.

 

So I started off with a remarkably nasty case of food poisoning from a reputable wraps and sandwiches franchise (which I will not name), and ended with a diagnosis that changed my life forever. The first 24 hours of running to the toilet, sitting on the toilet, feeling the hot lava fire of Hades erupt from my backside was brutal. But it didn’t stop. It continued for 36 hours, then 48 hours…then I noticed I was passing cherry kool aid.

 

“What the f*ck? I didn’t drink any cherry kool aid…”

 

I remember the car ride to my parents’ house (I was living in an apartment with a room mate at the time); my darling father wrapped the passenger seat with garbage bags and drove a good 30 km/h under the speed limit, took the smoothest roads and looked as tense as my asshole was trying to keep the hellfire inside. His knuckles were white. I mean white. And I’ve never seen that stoic man look so worried in my entire 27 years of knowing him at that point.

So I was sitting there, looking down at the lines on the road to pass the time as my gastric system burbled and gurgled violently, contemplating what it meant for my food poisoning symptoms to be lasting as long as they were. Was it a parasite? Did I somehow catch dysentary? Did I shit SO much that I pulled something or rendered my bowels defective?

The second he put the gear into park, I bolted out of the SUV and ran for the door. My mother had unlocked it knowing that I was going to need to marathon it to the toilet. And I pulled a Usain Bolt…

 

Cherry kool aid. And there was nothing else to it. As that day progressed, I was lazy boy chair bound. My darling father went to the store and bought me some adult diapers to wear, which I made quick work of and went through half that package by dinner time. The next day I had no energy, was barely awake for any conversations my mother tried to have with me, and it was only the beginning…

 

I ate Tylenol with codeine like they were M&Ms, and managed to make my way to my doctor’s office. After two trips to the bathroom I was finally able to sit on the examination table for her to listen to me and look me over.

“This sounds like Crohn’s Disease”, she told me. “I’ll refer you to a specialist. In the meantime, try to stay hydrated with…” she gave me a list of so much stuff. Told me to eat plain white rice and chicken stock.

 

She gave me requisitions for blood and stool samples, and I made my way to the nearest collections clinic.

 

“And this is called a ‘hat’, you will need to collect the stool in the bowl, here. Try your best to not get any urine in…”

 

I blinked as the technician handed me that plastic bowl resembling a Mayan headdress.

 

“I…I”m sorry, I have to poop in this?”

 

“That is correct. And use this wooden stick to scoop the sample into this cup. Be sure to write the time of collection, and bring it back here as soon as possible.”

 

F*CK

 

That was embarrassing.

 

So I got home, went to the toilet and lifted the seat to position the “hat” as per the instructions. I set the cup on the counter and opened the packaging for the wooden stick (over sized popsicle stick, really). Two more cups inside the big brown bag caught my attention and I brought them out. I later found out that these cups were for C Diff (Clostridium Difficile) and parasite testing, but was quite baffled at the time. They had little sporks (I kid you not, they are mini sporks) attached to their lids. I was going to collect my shit with sporks…What has my life come to?

 

In the not-so-distant future I returned to deliver my sample. I couldn’t quite figure out how I was supposed to poop in the hat so there I was awkwardly straddling the toilet because it just felt weird to sit down properly. It was like peeing in the woods, but far worse.

After a couple of minutes it was done. That was it. I made it. I accomplished what I felt was the impossible at that time, and what I had to do next was even worse.

 

When my brother was a baby, he decided it was a good idea to reach into his diaper and fingerpaint his room with his own poop. There is nothing cute about that, and there was nothing cute about what I was about to do, either. I gagged and teared up, but with shaking hands I managed to get my samples into their cups and take it all back to the lab in that brown paper bag.
At this point I can imagine you’re either grimacing, laughing, or feeling a little sick. Well just you wait until I tell you about the colonoscopy prep…next time.

Thank you, again, to /u/Hunhund. We all look forward to tales of your further adventures!

Hard to Accept: An IBD Soldier

I recently had the honor of talking to Reddit User /u/JustSomeoneWhoCares, who is submitting the first Contributor Content for GUTS.

His story about his struggle with Ulcerative Colitis, as previously posted on /r/CrohnsDisease:

I’ve just recently started using reddit. I’ve used it for awesome videos, funny pictures, interesting facts and tidbits of information, but I never thought about using it to vent until now. My story is one of disappointment, frustration, pain, agony, defeat, destruction, and finally, redemption.

I was diagnosed with Ulcerative Colitis when I was 16. It started out as a little pain. Then a little blood. Then more pain. More blood. I was embarrassed. I had no idea what was going on. I’ve always been a quite person. I flourish in social scenes, but I keep my cards close to my chest. I didn’t tell anyone. Not even my mother who is also a UC patient. I suffered in silence.

When I was a boy, I had always dreamed of being in the Army. Not the Marines, or Airforce, but the Army. My father was in the Army. My uncle was an Army medic who was killed in Vietnam. My grandfather had just been drafted into the Army during the Korean War until his experience as a car mechanic made him eligible to work on a thing called a “computer”. I had always dreams of being a military man. Back straight. Eyes forward. Chin out. I wanted to be something that little kids gawked at. I didn’t want to join for any other reason other than that was what I felt I was born to do.

I began physical training when I was 14. I began running to school, going to football practice, then running home. I mowed lawns to buy a weight set and began lifting. I was focused on becoming the quintessential picture of a soldier. I had dreams of being Special Forces. Those unnamed faces. Those shadow warriors. I wanted to lead the fight against my country’s enemies, because I felt, and still feel, America is the best place on the face of this Earth. I had already become a regular at our local recruitment office, just hanging out, getting to know the slang, seeing the way soldiers bred soldiers. I wanted to be them.

When I turned 16, nothing had changed. I was in top physical form. I had a wonderful girlfriend, fantastic grades, and was on track to joining straight out of high school.

Then I got sick.

It started as some pain in my abdominal region. I shrugged it off as the stomach flu. But the pain persisted. Become worse. Then the blood came. Just a little at first. Barely a tinge of red. I’m ok I told myself. It’s nothing. I’ll be ok. It’ll be ok. The first month passed with no relief. The pain only got worse. The water more red. After three months, I was barely standing. The body I had worked so hard to perfect was a shell of its former self. I had lost 35 pounds and enough blood that I had a yellowish tinge to my skin. My mother finally took my to the doctor where I came clean about when I had been suffering through. While relating my story, my mother began crying. She knew the reason for my pain. She had suffered through it herself. She knew I had Ulcerative Colitis.

How could this have happened? I wasn’t meant for this. I was meant to be a warrior. I was meant to be that man on the poster, that soldier on your campus. I was meant to be a soldier. I wasn’t meant to get sick. To bleed from invisible wounds. I was meant to defend my country. To fight for what I believe in. I wasn’t meant for this.

After a few tests, the admitted me into the ICU of the hospital. This was the first time I had morphine, and god it was delicious. The pure rush of nothingness and everything all at once through IV and into your soul.

I laughed and laughed.

Then came the blood transfusions. A stranger’s blood is all the stranger when it’s slowly sliding its way through your veins, becoming part of you. And oh the delicacies of hospital chicken broth. I was miserable. I longed to run. To jump. To fight. But “no” says the doctor. You need rest. “No” says my doctor. You need these tests. “No” says my doctor. You have Ulcerative Colitis.

What the f@#%.

And oh god, the tests. I can’t quite remember any of them save one.

The berium enema.

I’ll make a long story short.

They make you drink metal 7-up that makes you have to crap acid. “Just try to keep it down.”

They tell you not to use the restroom. “But I have UC doc, I shit regularly!”

They stick a plastic tube into your rectum. “…”

They inflate the tip of the tube that’s in your rectum. “!!!!!!!”

Then they have you walk over to this space age torture device that’s made out of the shiniest metal.

“Hold still”, says the technician. “And try not to move.”

I’ve never though myself a great multitasker, I usually focus on one task till it’s done. But trying to focus on not moving, while a balloon is inflated inside your inflamed rectum, while lying on a cold, flat, metal surface, while it’s rotating to various 45 degree angles, you tend to learn to multitask.

Because after all of that, you just really don’t want to shit yourself.

One thing that kept my spirits up in the midst of all of this, were the visits from Angie. Her raven hair. They way she always smelled of cocoa butter. Her shining, newly braces-free smile. She was the best part of my day. A kind word. A kiss on the cheek. She always was the best.

She brought me a giant card made out of a brown paper bag you get from the grocery store that a bunch of people from school had signed.

The greeting in it said, “Sorry you have leukemia.”

I laughed and I laughed.

Fast forward to graduation. I’m not as strong as I was, and I get winded a little quicker, and I’m still bleeding here and there, but I’ve got stranger’s blood. I’ll be ok.

I miss going to all the grad parties because I’m so weak. Angie falls asleep with me on the couch. She always was the best.

Two weeks later I stretch my legs and slowly make my way down to the recruitment office. My birthday was a week ago and I’m 18 now.

“Hello Sgt. Mendoza.” “Jesus, what the f@#% happened to you?” “Leukemia. Can you believe it?”

I open up about my diagnosis. The medications I’m taking. The stranger in my veins. My immune system that’s so bad ass it tries to f@#% me up. I lay it all out.

“Ok”, Mendoza says. “Let me talk to the doc and we’ll see what we can do.”

“Sounds good sir.”

We shake hands. It’s last time I’ll see him.

Two weeks later I get a call.

-beep- You have one missed call. -beep- Hello. This message is for Jacob. This is Sgt. Mendoza. I spoke to the doctor and unfortunately you will not be able to join. If you have any questions, feel free to call. Goodbye. -beep-

I sit in that 6 o’clock haze. The kind when the sun and the night are battling for dominance, and everything just gets grey.

But what am I supposed to do now. I call him back.

“But I haven’t planned for anything else. Is there anything I can do?” “Kid, you can’t even join the Coast Guard.” -click-

Fast forward two years. The decent was quick. I blamed myself. I blamed my mother. I blamed God and all of his f#@%ing infinite bullshit. I blamed Angie and the stress she caused. She left me. She always was the best.

Whiskey became my compatriot. My brother in arms. Marijuana became my unwinder. My chill mode. Ecstacy became my f#$% yeah. My OH F@#% YEAH.

I partied. I boozed and schmoozed. I laughed and I laughed.

The pain was constant, but I had accepted that it always would be, so why the f#%@ try.

I still read up on the war. I still called everyone “sir” and “ma’am”. I tried community college, but I couldn’t stay focused. It always seemed as if the classes were quieter. My stomach liked to party and wanted everyone to know.

I raged. I beat myself up. I stared at a knife, and wondered what it would be like to bleed from somewhere else.

I had been taking prednisone since being diagnosed, since there wasn’t much else to take.

I raged. I roid’ raged. I beat my fists and cursed the world. I spit and slavered. I shouted and seethed. I was frustration incarnate. I was crazy.

I had become a shell of my former self. Skinny and sad. Weak and wicked.

I stayed up late and slept in later. I thrashed and pushed my way to a greater high. A better time. All to escape the pain.

It all came crashing down around me one night. We were in L.A. We were f#$%#@ up on ecstacy. And I just remember holding hands with this girl while watching the paramedics try to revive this little raver girl who forgot to breathe. She didn’t make it. Something inside me cracked that night. I left the next morning with no word.

I told my mother of my drug-fueled rampage of self-loathing and remorse. She said it’s ok. We’ll get some help.

“So, tell me how you feel.”

That doctor wasn’t prepared. My fear. My hate. My sadness. My happiness. My crazy side. My compassionate side. My wild side. My calm side. “F#$% the world and f#$% UC.”

After a while, I finally got all of the hot air out of my lungs and finally had time to listen.

She was right. I shouldn’t blame myself. She made some sense. I’m not the first person to feel crazy because of things that are out of my control. She tried to talk to me about God. “Not really my bag doc, but I’ll listen if you talk.”

And listen I did. And it helped.

I quit the drugs. I quit boozin’ every night. I stopped hanging out with people who promoted my craziness. But most of all.

I stopped blaming myself.

Fast forward to now, I’m 3 years sober, with only the occasional Johnny Walker Black neat.

I smoke cigarettes, a nasty habit leftover from the crazy days, but I’m hiking every chance I get.

And lo and behold, my UC has been in remission for 2 years. It seems that my own blame I had placed upon my shoulders caused my system to get all screwy. I had nowhere to turn to send the blame. Blame for getting sick. Blame for losing Angie. Blame for all of the bad things I had done. But most of all, blame for not being able to pursue my dream. I wanted to be soldier. I wanted to be that man that kids stop and stare at. I wanted to be someone that could be idolized. Yes sir. Yes ma’am.

So I do, everyday.

I’m polite to everyone I meet. I open doors and offer it to anyone who’s behind me. I lead by example. And just because I don’t have a uniform, it doesn’t mean I can’t act like I do. I try to do my best in every aspect, in every way. Every single day.

Because that is what being a soldier means to me.

Thanks again to /u/JustSomeoneWhoCares for allowing GUTS to share.