Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that causes inflammation in the joints and it’s a type III response. There are many pain medications available for arthritis, because it is very painful and gets in the way of everyday life, since joints are used everyday in mobility. The way to determine if a patient has rheumatoid arthritis is by doing a blood test or x-rays, in which they search for rheumatoid factor. The treatments involve anti-inflammatory drugs. Based on the review articles it seems as though there are many factors that are involved, so there is a lot of research going into the causes of inflammation in the synovial area. There are also reactive oxygen species that play a part in the cause for inflammation, including O2¬¬-. Also, over expression of TNF-α reduces the activity of SOD, which is important in converting O2- into H2O2. Thus, as a treatment SOD mimetics are used to decrease peroxynitrite activity, influx of neutrophils at inflammatory site, and the release of proinflammatory cytokines. Researchers are also studies looking into supplements that can alleviate pain. However, it’s important to study the relationship between treatments and supplements, because they can affect each other.

When the immune system causes harm

As I have mentioned in my previous posts I am interested in Hepatitis C. There are currently over 170 million people infected with this virus worldwide. The long-term complication of Hepatitis C are cirrhosis and hepatocellular carcinoma. These complications often lead to liver transplant in the Hepatitis C patient.

As we learn more about HepatitisC and the immune response that is raised in attempts to clear the infection it becomes more clear that the inflammation intended to wipe out the virus is harming the liver and leading to cirrhosis and likely hepatocellular carcinoma.

Following viral infection there is activation of several pre-inflammatory mediators (chemokines -cytokines) that recruit immune cells into the liver. Once in the liver the immune cells are induced to generate an anti-viral immune response (T helper 1 cells secrete IFN-gamma and IL-2). If in the short-term the infection is not cleared the liver is set-up for a chronic inflammatory response (inflammation, regeneration and fibrosis). There is increasing evidence that different chemokines and receptors play roles at different stages in the infection.

Identification of serum markers for this inflammatory chemokine activity could help stage the chronic Hepatitis C viral process. Staging would assist with treatment options. Additionally, identification of an antagonist for this interaction would provide a treatment for liver inflammation, but would allow the virus to persist. Decreasing inflammation would potentially decrease cirrhosis and carcinoma. The concern is the cost of chronic Hepatitis C infection without the inflammation to hold it at bay.

There continue to be many unanswered questions for Hepatitis C, however the pieces of the puzzle continue to grow and fit into an explanation.

Reference -

Zeremski M, et al. The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J Viral Hepat. 2007; 14(10): 675-87

Wald, O., et al. Chemokines in hepatitis C virus infection: pathogenesis, prognosis and therapeutics. Cytokine. 2007; 39(1): 50-62

DMARDS

Hi everyone! As you may have seen after reading the articles this week on arthritis there is no cure. But there are treatments that help with the symptoms. There was one that was mentioned but not really discussed and that was DMARD. The acronym was thrown out there, but not really explained. So DMARD stands for Disease-modifying antirheumatic drug. This is a family of drugs that are used to slow the progression of rheumatoid arthritis. Although RA was the disease it was propagated for, many other diseases have had a response to them. Interestingly enough, Crohn's Disease is included in this list along with lupus. Ulcerative Colitis was not included though.

DMARDS include a vast array of drugs used for different purposes. There are thirteen drugs, which are used by different mechanisms. There were three that really caught my eye and they were adalimumab, etanercept, and infliximab. The three of these drugs treat RA by TNF inhibitor. Tumor Necrosis Factor (TNF) is thought to be a major contributor to RA for TNF alpha causes both cell damage and inhibits superoxide dismutases in the cell (SOD1). TNF inhibitors eliminate abnormal B cell activity which cause the apoptosis trigger by TNF alpha.
For more information on DMARDs:

http://www.webmd.com/rheumatoid-arthritis/guide/dmard-rheumatoid-arthritis-treatment

SOD memetics showing promise as future treatment for inflammatory joint disease

In a disease such as RA where proinflamitory cytokines like TNF-a are being over produced and reactive oxygen species are overwhelming the bodies natural enzymatic defenses.  The use of superoxide dismutase mimetic to supplement the bodies natural defense is showing promises as a possible addition to future therapeutic strategies for fighting inflammatory joint disease.  Along with the article entitled “reactive oxygen species and superoxide dismutase: Role in joint diseases” I also learned of a study by a Italian pharmaceutical company which reported 56% reduction in inflammation and 70% decrease in joint erosion in arthritic rats.   Both studies used the same SOD mimetic M40403.  These reports appear very promising but there still needs to be more testing before human trials can start. 

Optimal Timing for Surgery

Within the article titled, "Optimal Timing of Surgery for Inflammatory Bowel Disease," it discusses how necessary surgery is when compared to having ulcerative colitis and Crohn's disease. Only 20% of people diagnosed with ulcerative colitis are required to have surgery at one point of their illness, while 80% of the patients with Crohn's disease are obliged to have surgery. For patients with ulcerative colitis, after surgery they are permanently cured. The surgery many surgeons suggest their patients get is total proctocolectomy because other surgeries such as partial proctocolectomy, ileoanal pouch anastomosis, and permanent stoma will not permanently cure them from UC. Thus, many surgeons it is better to perform surgery at an early stage of UC. As of today, there is no surgery that can sure Crohn's disease, but it can be to treat symptoms when the patient is not responding to medical treatment. Even then, about 20% of the patients have reoccurring symptoms after 2 years and 80% of them will show signs of symptoms again after 20 years. The surgeons have seen that if the surgery is for lessening the effects of fibrostenotic disease and not perforating or fistulizing disease there will be less frequency in how many times the symptoms reoccur. Overall, deciding when to have surgery must be a thoroughly thought-out decision for both the surgeon and the patient. Most of the time, by delaying the time of surgery can tremendously increase the suffering and pain the patient experiences and reduce the chances of having a good outcome. In contrast, while delaying other medications could continue to improve the situation and eventually eliminate the need for surgery. In addition, if during the delay time the symptoms such as infections could be reduced and as a result lessening the risk of morbidity.
In a study done in England, it showed that the rate of mortality for patients who received surgery compared to ones who had not elected for surgery in either ulcerative colitis or Crohn's disease patients lived longer. Three years after surgery only 3.7% of patients with UC died after having surgery while the mortality for patients without surgery was 13.6%. Same with Crohn's disease patients, it increased significantly from patients that had surgery to patients who had not, 3.3% and 10.1% respectively. On the other hand, patients who had a emergency colectomy versus patients who elected themselves for the surgery had higher mortality rates. The study was done in the Oxford region with 23,464 patients from 1968 until 1996.

Sources:

"Threshold for Elective Colectomy Called Too High." Medical News.


Hodin R.S. "Optimal Timing of Surgery for Inflammatory Bowel Disease." SpringerLink.

Helminths and IBD

While we had a short ley article dealing with the use of helminths as a treatment for IBD, I thought it would be interesting to investigate their use further. Although usually the ingestion of worms would seem counterintuitive to treating disease, the helminth Trichuis suis has been found to be effective in relieving the symptoms of both Crohn's Disease and Ulcerative Colitis.

Unraveling the mechanism of disease for IBD has been difficult, however many studies have come to show the various biological systems which manifest these diseases. It has been found that CD is mostly a Th1 dominated immune response compared to UC. The idea behind the use of helminths is to steer the immune system from a Th1 to a Th2 mediated response. By doing this, it is possible to down regulate the Th1 response which is causing damage to the intestinal walls.

The study Trichuris suis Seems to Be Safe and Possibly Effective in the Treatment of Inflammatory Bowel Disease found the use of helminths to be beneficial in both CD and UC patients. In the study, after one treatment participants were found to have gone in to remission or had drastically lowered their CDAI or SCCAI scores. The study did show that with only one treatment, many experienced a flare up after 12 weeks, however if the treatment is repeated every 3 weeks the beneficial effects may be more lasting. One patient managed to remain in remission for over a year when treated regularly.

It seems that helminths may end up being an effective treatment for IBD, and some suggest that it may even provide a method for immunization. The link between sanitation and IBD prevalance may have to do with helminth contamination in water. Using this link, it may be possible to treat children with helminths in order to "teach" the body an appropriate immune response in order to prevent the autoimmune issues that are found in IBD.

Sources:
Trichuris suis Seems to Be Safe and Possibly Effective in the Treatment of Inflammatory Bowel Disease
Robert W. Summers, M.D., David E. Elliott, M.D., Ph.D., Khurram Qadir, M.D., Joseph F. Urban, Jr., Ph.D., Robin Thompson, M.H.A., and Joel V. Weinstock, M.D.
Department of Internal Medicine, James A. Clifton Center for Digestive Diseases, University of Iowa Health Care, Iowa City, Iowa; and The Immunology & Disease Resistance Laboratory, United States Department of Agriculture, Beltsville, Maryland

THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 98, No. 9, 2003
© 2003 by Am. Coll. of Gastroenterology ISSN 0002-9270/03/$30.00
Published by Elsevier Inc. doi:10.1016/S0002-9270(03)00623-3

Diminished HIV awareness

After our discussion of HIV in Tuesdays class and Dr. Cohen's comment about the younger generations lack of HIV awareness I found an article that proves his point. Recently a high school in suburban Missouri had a HIV scare. Accourding to health officals 50 out of the 1300 student population were potentially exposed to HIV. One student came forward to health officals saying he had HIV and other students may have been exposed. Students may have been exposed through sexual activity, intravenous drug use, tattoos and piercings.

One has to wonder if this would have occured if awareness of risky behaviors and HIV tranmission was higher. As Dr. Cohen stated, it seems as though the younger generation has less knowledge about HIV then in the 90's. This article also shows how little the general population knows about HIV. For example, a rival football team was concerned about playing the high school where the exposures occured and many students want to transfer out of the district.

This article shows how important education about HIV and risky behaviors is still needed.

http://www.comcast.net/articles/news-national/20081024/High.School.HIV/

Diagnosing IBD

I know it was a mentioned a couple times that Crohn's disease and ulcerative colitis have very similar symptoms, and that some doctors actually think they are the same disease. So it occurred to me that it might be difficult to differentiate the two during diagnosis. As everyone knows now from the papers we read the past two weeks, it is important to tell the difference between the two. Treatments for each of the diseases is different and the treatment for one can actually cause the other to flare up. So I did some research on how IBD is diagnosed in patients.

I found out that it isn't easy to definitively diagnose CD or UC. Sometimes they have to eliminate everything else including irritable bowel syndrome (IBS), bacterial, and viral infection. Physician's usually use a complete blood count (CBC), liver function tests, stool samples and an endoscopy or colonoscopy. The colonoscopy or endoscopy is usually the most diagnostic of all the tests. The infected areas of a Crohn's disease is patchy and can have a cobble stone appearance. The lesions can also be go deep into the intestinal lining. In ulcerative colitis the mucosa and sub mucosa layers of the intestinal wall.

References:

http://health.ucsd.edu/specialties/gastro/inflammatory-bowel-disease/diagnosis.htm

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastro/inflammatory_bowel/inflammatory_bowel.htm

A short interview with a patient suffering from Crohn's disease

So one of the guys I work with was diagnosed with Crohn's disease and after the articles last Monday I was curious about how his smoking affected him before and after being diagnosed. I asked him a series of questions ranging from smoking to symptoms to his treatment. This is what he told me.
During the hardest times of my disease i.e. during the large flare-up, my liver decreased about 40-50 percent functionality (lack of retaining vitamins, minerals, and nutrients). I did not have surgery; surgery is for the people that cannot control their flare-ups. I quit smoking, but the cessation of my smoking is what caused my Crohn's to flare-up out of nowhere. Since I smoked for quite a long time, they say that the reason the disease was dormant was because i smoked; that created a protective jelly film around my colon, which made it impossible for the white blood cells to attack. My symptoms during flare ups are: Blood in my feces, dizziness, lots of sweating, and many terrible cramp-like stomach aches. During remission, I have a few stomach aches, but nothing more.. maybe a bad poop every once in a while. Right now, I am taking immunosupressive drugs, i.e. 150mg azathioprine daily and a drug infusion called Remicade once every six weeks.

I plan on asking him a few further questions in regards to his diet and other things.

Diet Therapy in Crohn's Disease

When discussing general nutritional therapy, there are two primary forms used in medical practice, enteral and parenteral nutrition. Enteral nutrition, often referred to as tube feeding, allows for feeding into the GIT through a tube inserted nasally and fed into the stomach or small intestine. For long term usage, tubes can be surgically inserted into the stomach or small intestine through an opening made in the abdomen. Parenteral nutrition is the practice of feeding a person intravenously, and it completely bypasses the use of the stomach or intestines.

In terms of Crohn's disease, enteral nutrition is more often used as primary nutritional therapy. Parenteral nutrition is used in special cases or those of a higher severity. The overall goal for the use of diet therapy in Crohns is to correct any nutritional disturbances present and to help control the inflammatory response occurring. Remission rates of patients placed on enteral nutrition range from 53% to 80%; therefore, a direct anti-inflammatory effect of enteral nutrition in Crohn's disease is generally accepted. In one particular study, a decrease in the level of proinflammatory cytokines IL-1, IL-8, and IFN-gamma was observed in patients being treated through enteral nutrition. However, the direct mechanism of action for these observed anti-inflammatory effects is still not known.

Two mechanisms are currently proposed for the therapeutic efficacy of enteral nutrition in Crohns. The first mechanism is that the bowel rest allowed by the enteral feeding results in alteration of the intestinal flora and elimination/reduction of antigens. The second mechanism is that improvement in nutritional status by increase in nutrient intake and absorption aids in the induction of remission and reduction in intestinal protein loss.

Enteral nutrition usually has low compliance among adult Crohn's disease patients. Many find tube-feeding to be inconvenient, and a higher percentage of patients are more responsive to other medical treatments. Often enteral nutrition is seen as an effective adjuvant treatment in many cases. Enteral nutrition is far more widely used in the treatment of children with Crohns, and is often necessary to ensure proper nutrition and growth status.

Parenteral nutrition is used in cases of more severe disease when total bowel rest is a recommendation. It is also used in cases where patients have a poor tolerance to enteral nutrition; however, it is never recommended as a sole therapy in Crohn's disease.

Reference:
Moorthy D. Cappellano KL. Rosenberg IH. Nutrition and Crohn's disease: an update of print and web-based guidance. Nutrition Reviews. 2008; 66(7): 387-397.