Rheumatologists typically use drugs that either reduce the amount of uric acid a patient is making… or they give them a drug that makes them pee the uric acid out. The target is to get the uric acid in the blood down to 6mg/dL.
Probenecid is the drug of choice to make patients pee the uric acid out. It is generally safe but shouldn’t be used for patients with abnormal kidney function, a history of kidney stones, during aspirin therapy, and in those who already pee out a lot of uric acid. Patients should drink plenty of fluid.
Benzbromarone is a drug that also acts as a uricosuric agent (makes patients pee uric acid out). It is not FDA-approved. And, unfortunately, it can be extremely toxic to the liver.
Allopurinol is a drug that suppresses uric acid production. While it’s effective, it’s also potentially toxic with side-effects including severe rash, liver damage, bone marrow toxicity, and hypersensitivity. It should be started at a low dose and slowly increased.
Patients started on either probenicid or allopurinol often have flares of gout. Therefore, they should also be treated with colchicine, a drug that prevents flares of gout in patients who are started on anti-gout meds. Once the target uric acid level is achieved and maintained for 6 months, colchicine prophylaxis can be discontinued.
Febuxostat is a new alternative to allopurinol. It was FDA approved in March 2009 and marketed as Uloric. Uloric is an oral tablet that comes in both 40 mg as well as 80 mg strengths. Allopurinol is excreted primarily by the kidney while febuxostat is metabolized by the liver. Therefore, febuxostat can be administered in patents with less than normal kidney function.
Its efficacy at attaining a serum uric acid level of 6.0dL or better and side-effect profile seems to be somewhat better than that of allopurinol, and is an alternative to allopurinol in patients who are allergic to that drug. The only drawback is that there may be a higher incidence of cardiovascular events in patients taking high dose febuxostat.
Uricase is a substance that breaks down uric acid. It’s used in Europe to prevent the high levels of uric acid that can occur in the blood of patients with cancer who are receiving chemotherapy and also in some patients with treatment-refractory gout.
A recombinant form of uricase made from a fungus, called Aspergillus, has been FDA-approved for use in patients undergoing chemotherapy who may develop massive amounts of uric acid in the blood with treatment. The problem is that it induces significant immune reactions in patients and can cause anaphylactic shock.
A type of uricase preparation linked to polyethylene-glycol is currently being studied in clinical trials for gout.
The angiotensin receptor blocker losartan (Cozaar), used for hypertension, and the triglyceride-lowering agent fenofibrate (Tricor) have moderately potent uricosuric effects.
One study of 10 patients with severe gout treated with the anakinra, a drug that blocks a protein messenger called IL-1, substantially reduced pain in all patients within two days, without side effects. Clinical signs of inflammation were reduced in 9 of 10 patients by the third day of treatment.
So… the future looks pretty bright for this old disease. Right now I’m using alot of febuxostat because I have quite a few patients with gout who’ve had allergic reactions to allopurinol. Plus, alot of people with gout have less than normal kidney function, so it’s nice to have a drug where that isn’t quite such an issue.
Simponi (golimumab) was just approved by the FDA for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This is the first drug (to my knowledge) that was approved for all three indications at one time.
Simponi is a TNF-inhibitor, similar to Enbrel, Humira, and Remicade. It’s a human monoclonal protein directed against TNF. The major difference is that it is administered subcutaneously once a month.
The precautions and potential side-effects are similar to that of other TNF-inhibitors. The drug is manufactured by Centocor, a subsidiary of Johnson and Johnson. There is a patient assistance program available.
With the trend towards more self-injectables, this is a good addition.
More information is available at www.SIMPONI.com.
Other drugs in the wings for RA include Cimzia, a PEGylated- TNF inhibitor, and Actemra, an IL-6 inhibitor.
I recently had a question from a person with psoriatic arthritis who had had a couple of rheumatologists differ in their approach to the condition. He asked my opinion. This was my reply:
My approach to psoriatic arthritis is:
Stage the disease by getting an MRI with gadolinium of the most affected area
Begin Methotrexate (MTX) ASAP
Add on a TNF inhibitor fairly quickly (within the first 6-12 weeks)
There are no significant differences between Enbrel and Humira as far as side-effects; however, I feel both Humira and Remicade act faster on both the skin and joint manifestations of psoriatic arthritis than does Enbrel
All TNF inhibitors carry with them the possibility (and I stress the word “possibility”) of reactivation TB, susceptibility to fungal infections such as histo, cocci, etc.
I have my patients hold their MTX and TNF inhibitors if they have an active infection of any type (skin, URI, UTI, etc.) until the infection is cleared.
He asked another question about malignancy risk with MTX and TNF inhibitors.
My answer was:
MTX is not associated with malignancies above and beyond what would be expected due to arthritis alone.
The data regarding TNF inhibitors is still not completely clear. Like every effective medication, there are risks and benefits.
Only you, as the patient, can make the final decision.
The point is that we don’t know about malignancy risk with TNF inhibitors. While the data so far looks relatively good so far, we don’t know what can happen 20 to 30 years down the road. Nonetheless, in diseases like RA and psoriatic arthritis, the risks of the disease (early cardiovascular complications such as heart attack and stroke, shortened life expectancy, etc.) appear to far outweigh the risks of malignancy… at least for now.
When your knee hurts, getting relief is all that’s on your mind. Getting the right relief, though, depends on knowing what’s wrong. The correct diagnosis will lead to the correct treatment.
Know Your Knee!
The knee is the largest joint in the body. It’s also one of the most complicated. The knee joint is made up of four bones that are connected by muscles, ligaments, and tendons. The femur (large thigh bone) interacts with the two shin bones, the tibia (the larger one) located towards the inside and the fibula (the smaller one) located towards the outside. Where the femur meets the tibia is termed the joint line. The patella, (the knee cap) is the bone that sits in the front of the knee. It slides up and down in a groove in the lower part of the femur (the femoral groove) as the knee bends and straightens.
Ligaments are the strong rope-like structures that help connect bones and provide stability. In the knee, there are four major ligaments. On the inner (medial) aspect of the knee is the medial collateral ligament (MCL) and on the outer (lateral) aspect of the knee is the lateral collateral ligament (LCL). The other two main ligaments are found in the center of the knee. These ligaments are called the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL). They are called cruciate ligaments because the ACL crosses in front of the PCL. Other smaller ligaments help hold the patella in place in the center of the femoral groove.
Two structures called menisci sit between the femur and the tibia. These structures act as cushions or shock absorbers. They also help provide stability for the knee. The menisci are made of a tough material called fibrocartilage. There is a medial meniscus and a lateral meniscus. When either meniscus is damaged it is called a “torn cartilage”.
There is another type of cartilage in the knee called hyaline cartilage. This cartilage is a smooth shiny material that covers the bones in the knee joint. In the knee, hyaline cartilage covers the ends of the femur, the femoral groove, the top of the tibia and the underside of the patella. Hyaline cartilage allows the knee bones to move easily as the knee bends and straightens.
Tendons connect muscles to bone. The large quadriceps muscles on the front of the thigh attach to the top of the patella via the quadriceps tendon. This tendon inserts on the patella and then continues down to form the rope-like patellar tendon. The patellar tendon in turn, attaches to the front of the tibia. The hamstring muscles on the back of the thigh attach to the tibia at the back of the knee. The quadriceps muscles are the muscles that straighten the knee. The hamstring muscles are the main muscles that bend the knee.
Bursae are small fluid filled sacs that decrease the friction between two tissues. Bursae also protect bony structures. There are many different bursae around the knee but the ones that are most important are the prepatellar bursa in front of the knee cap, the infrapatellar bursa just below the kneecap, the anserine bursa, just below the joint line and to the inner side of the tibia, and the semimembranous bursa in the back of the knee. Normally, a bursa has very little fluid in it but if it becomes irritated it can fill with fluid and become very large.
Is it bursitis… or tendonitis…or arthritis?
Tendonitis generally affects either the quadriceps tendon or patellar tendon. Repetitive jumping or trauma may set off tendonitis. The pain is felt in the front of the knee and there is tenderness as well as swelling involving the tendon. With patellar tendonitis, the infrapatellar bursa will often be inflamed also. Treatment involves rest, ice, and anti-inflammatory medication. Injections are rarely used. Physical therapy with ultrasound and iontopheresis may help.
Bursitis pain is common. The prepatellar bursa may become inflamed particularly in patients who spend a lot of time on their knees (carpet layers). The bursa will become swollen. The major concern here is to make sure the bursa is not infected. The bursa should be aspirated (fluid withdrawn by needle) by a specialist. The fluid should be cultured. If there is no infection, the bursitis may be treated with anti-jnflammatory medicines, ice, and physical therapy. Knee pads should be worn to prevent a recurrence once the initial bursitis is cleared up.
Anserine bursitis often occurs in overweight people who also have osteoarthritis of the knee. Pain and some swelling is noted in the anserine bursa. Treatment consists of steroid injection, ice, physical therapy, and weight loss.
The semimembranous bursa can be affected when a patient has fluid in the knee (a knee effusion). The fluid will push backwards and the bursa will become filled with fluid and cause a sensation of fullness and tightness in the back of the knee. This is called a Baker’s cyst. If the bursa ruptures, the fluid will dissect down into the calf. The danger here is that it may look like a blood clot in the calf. A venogram and ultrasound test will help differentiate a ruptured Baker’s cyst from a blood clot. The Baker’s cyst is treated with aspiration of the fluid from the knee along with steroid injection, ice, and elevation of the leg.
Knock out knee arthritis… simple steps you can take! Younger people who have pain in the front of the knee have what is called patellofemoral syndrome (PFS). Two major conditions cause PFS. The first is chondromalacia patella. This is a condition where the cartilage on the underside of the knee cap softens and is particularly common in young women. Another cause of pain behind the knee cap in younger people may be a patella that doesn’t track normally in the femoral groove. For both chondromalacia as well as a poorly tracking patella, special exercises, taping, and anti-inflammatory medicines may be helpful. If the patellar tracking becomes a significant problem despite conservative measures, surgery is need.
While many types of arthritis may affect the knee, osteoarthritis is the most common. Osteoarthritis usually affects the joint between the femur and tibia in the medial (inner) compartment of the knee. Osteoarthritis may also involve the joint between the femur and tibia on the outer side of the knee as well as the joint between the femur and patella. Why osteoarthritis develops is still being scrutinized carefully. It seems to consist of a complex interaction of genetics, mechanical factors, and immune system involvement. The immune system attacks the joint through a combination of degradative enzymes and inflammatory chemical messengers called cytokines.
Patients will sometimes feel a sensation of rubbing or grinding. The knee will become stiff if the patient sits for any length of time. With local inflammation, the patient may experience pain at night and get relief from sleeping with a pillow between the knees. Occasionally, locking and clicking may be noticed. Patients with osteoarthritis may also tear the fibrocartilage cushions (menisci) in the knee more easily than people without osteoarthritis.
So how is the arthritis treated? An obvious place to start is weight reduction for patients who carry around too many pounds.
Strengthening exercises for the knee are also useful for many people. These should be done under the supervision of a physician or physical therapist.
Other therapies include ice, anti inflammatory medicines, and occasionally steroid injections. Glucosamine and chondroitin supplements may be helpful. A word of caution… make sure the preparation you buy is pure and contains what the label says it does. The supplement industry is unregulated… so buyer beware!
Injections of the knee with viscosupplements – lubricants- are particularly useful for many patients. Special braces may help to unload the part of the joint that is affected.
Arthroscopic techniques may be beneficial in special circumstances. Occasionally, a surgical procedure called an osteotomy, where a wedge of bone is removed from the tibia to “even things out,” may be recommended. Joint replacement surgery is required for end stage knee arthritis.
Research is being done to develop medicines that will slow down the rate of cartilage loss. Targets for these new therapies include the destructive enzymes and/or cytokines that degrade cartilage. It is hoped that by inhibiting these enzymes and cytokines and by boosting the ability of cartilage to repair itself, that therapies designed to actually reverse osteoarthritis may be created. These are referred to as disease-modifying osteoarthritis drugs or “DMOADs.” Genetic markers may identify high risk patients who need more aggressive therapies.
Newer compounds that are injected into the knee and provide healing as well as lubrication are also being developed. And finally, less invasive surgical techniques are also being looked at. Recent technological advances in “mini” knee replacement look very promising.
It’s been more than 8 months since Warren Suker had a stem cell procedure for osteoarthritis of the knee. He says, “I’m feeling like a young school boy. I am slowly building my strength back up with low impact exercises. My range of motion is incredible, and I’m living my day… not worrying about knee pain. I am looking forward to having the other knee done in the spring.”
Attention: AOC now specializes in procedures using platelet-rich plasma and stem cells.
Dr. Wei states, “regenerative medicine has flown under the radar. First used by laboratory scientists and then veterinarians, it has surfaced in the last few years as a legitimate healing technique for those with osteoarthritis.”
He adds, “the two components used are platelet-rich plasma (PRP) and stem cells. What platelet rich plasma and stem cells do is halt and reverse nagging soft tissue injuries and accelerate healing at breakneck speed.”
… So how is it done?
Dr. Wei says, “stem cells are prepared from a bone marrow specimen obtained from the iliac crest of the hip using local anesthetic. They are then injected into a joint for the purpose of regenerating either cartilage, tendon, or ligament depending on what has been injured – extending the natural life of that joint.” He continues, “but this procedure goes one step further as we inject PRP, which contains multiple healing and growth factors. It is obtained from a simple blood sample.
Stem cells have growth factor receptors on their surfaces. Growth factors from the PRP bind with these receptors, and make the stem cells start to divide and multiply.
“Most importantly we use ultrasound needle guidance. This means we deliver the PRP/stem cells to the exact location needed to get the best result with the least discomfort to the patient.”
Combining PRP and stem cells sends healing and recovery into warp drive.
David Krieger shares, “my knee pain was placing considerable restraints on me when I would exercise or want to go running. When I had heard about the stem cell procedure, I decided to find out if this would be helpful for me. I had the procedure in October 2008. It was quick, uncomplicated, and non-painful. I didn’t feel a thing! It’s been three and a half months now, and I appear to be getting stronger and stronger everyday. I have no pain in my knee and I feel terrific. I haven’t quite resumed a full run on the treadmill, but I’m walking pretty quickly. I’m 65 years old, and I believe that the results have been life altering.”
Dr. Wei goes on to say, “PRP and stem cells have helped our patients with tendonitis, bursitis, and osteoarthritis recover and get back to doing the things they enjoy like gardening, golf, fishing, skiing, basketball, and so on, because stem cells make new healthy tissue.
This procedure promotes a surge in healing!
Sherrill Pirsamadi traveled from Houston, Texas to have this procedure performed recently. She says, “three months ago, I had a procedure performed on my left shoulder where Dr. Wei injected stem cells to help re-grow my cartilage and provide me with some mobility and relief. Six months ago, I had traditional surgery on my right shoulder, to help give me some mobility back! Today, I can say that my left shoulder is wonderful! I have movement, and I am not feeling any discomfort or pain. It’s amazing! Sadly, my right shoulder seems to be taking much longer to heal, and still requires that I take pain medication to get through the day. The stem cell procedure is less complicated and seems to have been a far better improvement over the traditional procedure performed on my right shoulder.” Just this past month the Pirsamadi’s returned to AOC where her husband, Javad, had a knee procedure performed. Stay tuned for his results…
Please contact our office at 301-694-5800 to find out if you can benefit from this procedure.