Posted 11/16/2012 7:30 PM (GMT 0)
When I first investigated the purple toilet stains, Google sent me to several posts on this as well as other forums. That is when I noticed that a number of others with UC or Crohn's have also posted a similar experience. I was actually very surprised that the purple stains were dismissed so readily as being caused by mesalamine. I am not saying that it was impossible for mesalamine to be the culprit, rather it is highly unlikely that mesalamine has the ability to stain urine that has been described.
Here is what I was thinking when I first read everyone's posts regarding this.
Certain drugs can stain your urine and there is plenty of documentation of the mechanism responsible. Generally speaking it is not a large leap to expect a drug that contains an AZO bond to be able to change the color of urine. Phenazopyridine, nitrofurantoin, and sulfasalazine are 3 good examples of drugs that contain this type of bond and can darken the color of urine. However, I knew that mesalamine was not an AZO dye so if it was changing the color of urine it had yet to be explained why.
Unlike sulfasalazine which can be used used for arthritis, mesalamine preparations are not absorbed very well systemically, which is why they are a good choice to treat inflammation in the colon. The drug stays right where it needs to be. On average only 20% of orally administered mesalamine is absorbed and the metabolites have not been shown to change color of urine either.
Then, I remembered seeing red urine and purple pee stains well before I was put on Asacol just prior to my diagnosis of UC when I was in college. I had asked my physician about the purple stains and the red pee, and I submitted a urine sample along with some blood work. I was told not to worry about it, and that red urine was not uncommon after eating beets. Back then, I ate beets on a regular basis, and the doctor had no way of knowing this, so it was not hard to accept his explanation.
If none of this information was convincing enough, I poked even further. There is no documentation in the package inserts of the various mesalamine manufacturers that indicate it's responsible for changing the color of urine. However, since so many of you suggested that mesalamine was responsible I still decided to call Warner-Chilcot, Shire, and Medeva (Proctor and Gamble) to see if they had collected any post marketing data or have any additional information about purple pee stains or red urine associated with their individual mesalamine preparations. They were all very helpful, some even called me back (after conducting further research) a few days later but they all concluded that mesalamine does not have the ability in vivo to cause red pee or purple pee stains on the toilet.
If someone can provide me with documentation that mesalamine can cause urine color to change to purple please do so because I haven’t been able to find it. Even the food colorings used in the various tablets are not responsible for changing urine color, they are the same colorings used in commercial products most of consume. Can you imagine the rainbow pee and the stains that would be left on the toilet if someone at too many m&m’s? Ok so now that I was sure mesalamine wasn’t the cause, I had to get to the bottom of the cause.
After I did some more digging, I stumbled across porphyria as a possible explanation for causing the purple pee stains on the toilet. I tried to disprove porphyria as the cause with just as much conviction, but the more I tried to disprove it, the more it became likely that porphyria was actually the cause of the severe abdominal attacks that I was having and it tied everything else together perfectly, I could not ignore it.
Several years back I was put on a statin drug to control my cholesterol, after a few weeks I had to discontinue the drug because it was causing rhabdomyolysis, a very rare but serious side effect associated with the statins measured by elevated Creatine Kinase (CK) enzymes. In most people, after discontinuing the statin drug, CK enzymes should return to normal in a few weeks. My levels never returned to normal and it has puzzled every doctor that I have seen for the last 8 years. This may seem irrelevant, but is a feature noticed in porphyria.
about 7 years ago, I had red urine and acute abdominal pains so severe that I passed out and woke up in the emergency room of the hospital. The doctors couldn’t figure out what was wrong and thought I was making up the pain to get drugs. It felt like they didn’t take me seriously. I didn’t want to add another complaint but I also felt tightness in my chest and asked a nurse to hook me up to an ekg machine. The instant she connected the final lead she sprinted out of my room to grab the attending. Apparently, I was in a-fib and they all had missed it. My heart rate was hovering around 210 – 240 beats per minute. They tried to cardiovert me with a calcium channel blocker (this is a very significant detail as it related to porphyria) that did not help two hours later the drug was changed to a beta blocker and after about 5 minutes it my heart was back to normal sinus again. Tachycardia/arrhythmia/a-fib has also been known to accompany porphyria.
Ok so far I found nothing to disprove porphyria, but still have nothing to prove it. But wait, there is more…
In the spring of this year while I was on weight watchers and losing weight rapidly, I was hospitalized again with extremely severe abdominal pain that I knew was not directly related to UC but the exact spot of the pain was hard to localize. It felt like a thousand flaming swords spinning in my gut, but at times it also felt like it was coming from my gall bladder. The doctors worked me up for gall bladder problems every way they could. I had all these tests done before and they always came back with negative results this time was no exception. So they decided to do an upper endoscopy and they found a large duodenal ulcer. I was discharged a few days later and put on meds to treat the ulcer. My GI doctor was away on vacation at the time I didn’t get a chance to speak until a couple of weeks after I was discharged. He put me on an antibiotic called clarithromycin and increased my dose of omeprazole. I also started to notice that since I started weight watchers the toilet was becoming stained more frequently, although I had not necessarily noticed red urine. After I started taking the clarithromycin and the increased dose of the omeprazole, I noticed that the purple stains were becoming more pronounced and my urine was starting to change to red. I made it a point to avoid eating anything red at all. I even looked at my weight watcher log to see if I had eaten anything red that I could correlate with my pee color, but I found nothing. Eventually, my urine was completely red and it stained the toilet instantly when it hit the bowl. By this time I had lost close to 50lbs on weight watchers in a little over 2 months. The red urine went on for several during late to mid May until the beginning of June. The stains were all over the toilet it was embarrassing and I hadn’t eaten a beet or rhubarb in over a month. Then I started to get constipated, and my stomach started to hurt slightly, before I knew it, tremendous abdominal pain, took over, I couldn’t breath, and I was overwhelmed by nausea as well. This was one of the most vicious attacks that I had ever had. My wife was out of town, I had to call my parents to drive me to the hospital. The doctors could not give me enough narcotics to quell the pain. I was admitted again, and again, they preformed every test and found nothing. I was sent home after spending 5 days there. The day after I was discharged, I stepped on my scale and my total weight loss equaled 65lbs since I started on weight watchers. That night, I had an attack so severe that I realized a completely new level of pain higher than the previous one that I had just described as vicious. I wound up in the hospital and was admitted again, but this time the doctors blew me off completely. They told me that I was a drug seeker and that I made everything up and that there was no reason to keep me there. I was given a psychiatric diagnosis and discharged. Even though I was in terrible pain, I wanted to get out of that place as fast as possible. I completely lost faith in the health care system. I went home, by this time I had forgot all about the red urine or the purple stains on the toilet, that was the last thing on my mind.
A week or so later is after my wife and I were painting the house and I noticed purple pee stains on the toilet is when I put all the pieces together that pointed to porphyria. Paint fumes can also induce porphyria.
Porphyria is a disorder in heme synthesis. Heme is a porphyrin ring and it’s synthesis is a highly conserved through out nature. The most well known role of heme is the one that it plays in hemoglobin. Heme is the “activating” ligand that gives hemoglobin it’s unique allosteric properties to enable the exchange of oxygen and carbon dioxide in respiration. However, many other proteins in your body need heme to function, and are designated as hemoproteins. The Cytochrome P 450 (CYP 450) enzyme system responsible for metabolizing drugs and foreign substances that we ingest is one of these hemoproteins. If we are exposed to a drug that is metabolized by this enzyme system your body simultaneously up-regulates both the transcription of the relevant apo-CYP 450 (apo- meaning without heme, or inactive) and heme that the enzyme will need to function. In some forms of porphyria this can be a huge problem because if you do not have enough heme floating around there can be problems.
Furthermore, these cytochrome enzymes are present in the intestines and the colon. These enzymes need heme to function and a depleted supply of heme may not be a good thing since these enzymes mediate a process called apoptosis, which is thought to play an important role in inflammatory bowel disease. There are a few other roles that heme has in IBD as well.
This is getting way too long and is probably hard to read so let me sum up how to tell if you have porphyria.
There are several different types of porphyrias. A 24 hour urine sample can test for some of the porphyrias but it has to be conducted by an experienced lab, and the sample must be completely protected from light and refrigerated. Meaning that you have to wrap the sample jug in aluminum foil and pee in it in the dark, then store it in your refrigerator until you fill it up and bring it to the lab in a cooler. Then you have to make sure that the lab knows how to handle it or all your trouble will be for nothing.
To sum up, here are some things that can induce porphyria, usually takes more than one factor to cause an attack
Fasting, exercise, and dieting
Drugs that are strong substrates for CYP 450 enzymes
Stress
Alcohol, (red wind, whiskey)
Paint fumes
Female sex hormones are a big factor in women
80-90% of people with the gene that causes porphyria don’t know they have it or never have symptoms. It usually takes more than one factor to tip the scale enough in the right direction to trigger an attack. It’s not uncommon for people with porphyria to be accused of being a drug seeker like I was when the doctors had no clue what was going on. I had to explain what porphyria was to my doctor before he finally ordered a test for it. After the first test came back negative my doctor refused to give accept it, we had to test multiple times before it could be confirmed.
If you have Ulcerative Colitis, Crohn’s, Lups. Etc… and you have noticed purple stains on your toilet or red urine then it would be a good idea to rule out porphyria especially if you have unexplained abdominal pain.