Below are transcripts of lectures that Dr. David Kaufman has given to laypeople about interstitial cystitis and how it is diagnosed and treated.
Good afternoon. I am Nancy Taylor, the new Executive Director of the Interstitial Cystitis Association. I am very proud to have been chosen to lead this wonderful organization. The people most responsible for coordinating the program are James Loney, Ann Chesnut, who is also the editor of our newsletter, the ICA Update, Carolyn Coogan, and Ellen Goldstein. I also would like to thank Alza Corporation, manufacturer of Elmiron®. They have helped us underwrite the majority of the costs associated with this program. I would also like to thank and acknowledge the Fishbein family. Through the Fishbein Family Foundation, last year and this year, they will have contributed $400,000 toward IC-specific research. All this wonderful research that is now occurring is very exciting and I know that a great many of you are very encouraged by some of the work that is being done. I think there is a bright future for people with IC.
Our first speaker this afternoon is Dr. David Kaufman. Dr. Kaufman is an Assistant Professor of Clinical Urology at Columbia University School of Medicine and an Assistant Attending Physician at St. Luke's Roosevelt and Columbia Presbyterian Medical Center. In his recently opened Manhattan private practice, he shares his office with a female gynecologist who specializes in pelvic pain and vulvodynia. In the summer issue of our ICA Update, we welcomed Dr. Kaufman as a recent contributor to our Doctors' Forum. It is my pleasure to introduce you this afternoon to Dr. David Kaufman.
My goal this afternoon is to give all of you an overview of interstitial cystitis (IC). I don't doubt that many of you know as much as most of us up here, but there are some new treatment modalities that are very exciting, and I will cover those as well.
We are going to talk about the painful bladder. IC is the official term for it. I would like to dispel some myths that too many people have. I am sorry to admit that many of my colleagues in urology still believe some of these myths. It is your job as educated consumers to teach your urologists that there are new things happening with IC. It is not a rare disease, it is not necessarily difficult to diagnose if we understand this disease, and it certainly is not difficult to treat, and that is even more true these days. I don't want to belabor you with statistics, but suffice it to say that the harder we look for patients with this disease, the more we find. It is estimated now that there are probably close to 1,000,000 people whom we have already diagnosed with IC. This is just the tip of the iceberg. The more we spread the word and the more we educate our primary care doctors and gynecologists, the more patients we will be able to find and, most importantly, the more patients we will be able to help.
I will go over some basic demographics about IC. The average age range is marked at forty-four. In my practice, this number is way off. The majority of my patients are in their late twenties or early thirties. I think it is a credit to the New York City medical establishment that we are spreading the word and doctors are beginning to recognize that this disease exists. We are catching it a little earlier in metropolitan centers, but unfortunately, that is not the case for the rest of the country. Our patients are mostly female, but the more we start thinking about the existence of this disease in our male patients, the more men we find with IC. In urology, we have a lot of males whom we diagnose as having chronic prostatitis. Clearly, many of them do have prostate infections. We are finding that a high percentage of these patients, whose cultures are negative and who have symptoms reminiscent of IC, don't have prostate infections; they have interstitial cystitis. We need to make other urologists understand this. When I give a talk similar to this to urology grand rounds around the country, I emphasize to my colleagues that they have to start looking at their male patients and start thinking about this disease.
I don't think I have to tell anybody in this audience that our patients with IC spend a lot of time in the bathroom. The average number of voids per day is sixteen. We use a rough number of 8-10 voids as minimum criteria for IC. Many of our patients go to the bathroom much more often than that. The average voided volume is 100 ccs. As soon as a little bit of urine gets into the bladder, it irritates the lining of the bladder and they get severe urgency and need to urinate. I think of all the symptoms of IC, the one that is clearly the most socially devastating is what doctors call dyspareunia. We understand this as pain during intercourse. Needless to say, I have seen many relationships and marriages on the rocks because of IC. It is very important that this disease gets diagnosed so we can help these patients. It takes a tremendous social toll.
This is my favorite slide of the whole talk. This is a new concept to many urologists. It is hypothetical but I think it makes sense to so many of us. The gist of this slide is that we believe that it is those young women who start off in their late teens or early twenties with recurrent urinary tract infections (UTI) which don't get adequately addressed. They don't get rid of the infection. It is MY idea that over time, not all of these patients, but a percentage of these patients, will evolve down this unfortunate roadway to IC. This is moderate, or classic, IC. The NIH has very strict criteria for IC, which require more in the way of symptoms. The advanced case of IC (what I call mature IC) is a combination of IC and pelvic floor dysfunction. This is an important part of that disease. Urologists used to perform cystectomies (removal of the bladder) in severely affected patients with IC, and a sizable percentage still had bladder pain following their surgery. I think the reason is that, in addition to their IC, they also had pelvic floor dysfunction (PFD), a terrible spasm of the pelvic floor muscles. We call this pelvic pain and the patient interprets it as bladder pain. Colorectal surgeons have been dealing with this entity for years. They call it something different, levator ani syndrome. It is basically the same pathology. It is a neuropathic change that occurs to the nerve endings that go to the bladder, bounce back to the spinal cord, and come right back down to the muscles surrounding the bladder and cause those muscles to go into spasm. In patients with mature IC, you can do anything to the bladder They can have a great response to medications, but if you don't address the PFD, they will still have pain with intercourse and pelvic pain. If some of you are involved in therapy for the bladder with IC and you are still having symptoms, ask your doctor about PFD. We will talk about treatment for this later.
When our patients come to us with urinary frequency, urgency, negative urine cultures and pelvic and bladder pain as well as dyspareunia, our medical colleagues need to start suspecting a diagnosis of IC. There are a lot of potential etiologies, but to make a long story short, we believe right now that epithelial dysfunction is the cause of IC, at least in a high percentage of patients. The bladder is lined by a waterproofing layer (urine proofing), the GAG layer (glycosaminoglycan layer). The physician who first came up with this theory, Dr. C. Lowell Parsons in San Diego, likes to refer to it as the "slime layer." This is the layer that prevents the urine from leaching through the wall of the bladder. We believe that in IC there are defects in this waterproof coating of the bladder. It allows urine and all the noxious metabolites within the urine to leach through the epithelium. It can cause scarring and irritation in the lamina propria and also irritate nerve endings. This sets up a vicious cycle of inflammation that causes the symptoms of pain and urgency. Here is a photomicrograph that shows the defect in the GAG layer. The pathophysiology of the symptoms of this disease starts with a damaged urothelium. I believe the chronic exposure to infection and bacteria over time (5-10 years) eventually causes damage to the GAG layer and allows for all the other problems to happen.
Many of you know that when you eat spicy foods or drink alcohol or caffeine that those foods set you off. It is my theory that it has to do with an ion called potassium. Potassium is a metabolite within the urine that is the active ingredient that irritates the nerve endings. It depolarizes the nerve endings, and this starts the whole cycle of inflammation. The potassium gets in, causes inflammation, fibrosis, and it becomes a vicious cycle. That potassium depolarizes these nerve endings, and causes the secretion of neuropeptides. The one that we have evidence for and can measure is substance P. Substance P causes degranulation of mast cells, which have histamine and other inflammatory mediators. It just goes round and round. That is why patients with IC don't get better.
Let's talk about how we diagnose IC. Anyone with blood in their urine, persistent urgency, frequency, pain, dyspareunia, and negative cultures should be seen by a urologist. Many of our patients have had gynecologic surgery. Is that because the gynecologist caused some sort of damage in the bladder lining? Most likely not. It is because, when women get pain in their pelvis, they go to their gynecologist first. Until recently gynecologists did not know anything about IC so they did laparoscopies, and took out ovaries and uteruses. Many of our patients have had prior gynecologic surgery. Does it help them? Hardly ever.
There is definitely a modulation of symptoms during different phases of your menstrual cycle, irritative voiding symptoms, dyspareunia, and an association of vulvar vestibulitis. IC is to a urologist like vulvar vestibulitis is to a gynecologist. It is the same sort of disease; it is a similarly neuropathic disease. It starts with inflammation of perhaps the vestibular glands, and that inflammation, over a chronic period of time (whether it is yeast infections or bacterial vaginitis that caused it), causes a neuropathic change in the nerve supply, and basically causes the same PFD. It feeds back onto the same muscles (levator and pubococcygeal) and causes them to go into spasm. It is a similar disease. What makes it more relevant is that about 30% of patients with IC also have vestibulitis and vice versa. There is a lot to the correlation between these two diseases that we don't completely understand.
I do a pelvic exam and in my practice, this is the most telling sign. When I am referred a patient with the above symptoms, and when somebody who understands this disease does a pelvic exam, you can come up with a diagnosis just based on that. When examining the vaginal vault, lifting gently up against the bladder base, a patient who has no pathology won't feel a thing, a patient who has a mild urinary tract infection says it makes them feel like they need to urinate and in a patient with IC, you have to "peel them off the ceiling." It is a dramatic difference in signs. This is our opportunity to assess the presence of a mature case of IC, whether or not there is PFD. The examining fingers swing laterally within the vaginal vault and feel the muscles of the pelvic floor, the levator ani muscles and the pubococcygeal muscles. Obviously, the patient can't do this to themselves. You can introduce this concept to your doctor if she/he is not familiar with it. Upon palpation of the levator ani muscles, this will elicit a tremendously painful response when there is also pelvic floor dysfunction in addition to IC.
There is a new test that you should know something about. It is called the KCI sensitivity test. I am not certain this should be used as a diagnostic test for IC, but in a percentage of patients with IC, when a little bit of potassium chloride mixture is put in their bladder, they will have a tremendous inflammatory and painful response. That might be a marker for patients with IC who have a GAG layer defect. It might be a marker for patients with IC who are more likely to respond to drugs like Elmiron, and there is research ongoing to get a better understanding of this.
Right now I fully believe that to make a diagnosis of IC you have to go back to the standard diagnostic test, the cystoscopy with hydrodistention under anesthesia. As you all know, branding a patient with those scarlet letters of IC is not to be taken lightly. Before I do that, I like to make sure these patients have IC. In my book, the only way to do that is by doing it by the book. There is a silver lining to this procedure; about 40-50% of patients actually improve afterwards. However, for the most part, it is done for diagnostic purposes. When a hydrodistention is done, typically you can see glomerulations and petechial hemorrhages. A normal bladder clearly does not look this way. I believe there is only one disease that causes a picture like this and that is interstitial cystitis. Some of you will read about a diagnosis of a Hunner's ulcer. In the early 1900s, Dr. Hunner was one of the first doctors to describe IC. He described an ulcer, which I have never seen. What I have seen is just a big erythematous patch. I think to explain what Dr. Hunner was seeing you must go back to 1908, to the very early cystoscopes, which were probably using "candle power" to look inside the bladder. I don't think he achieved the same quality of optics we get today. We take biopsies of the bladder and ask for a mast cell count. We have already spoken about mast cells, which contain histamine. This is something we see in higher percentages in many patients with IC.
When we talk about treatment, the catchall word right now is multimodal therapy. We like to combine treatments. If Elmiron is our first line treatment, we like to combine it with another medication. If I do a hydrodistention and find a tremendous number of mast cells in the specimen, I know this patient has a lot of histamine and my multimodal therapy would probably combine Elmiron with antihistamines.
Why do some people feel better after a hydrodistention? We disrupt that defective lining and there is probably some regeneration of new tissue. Perhaps in the 40-50% of patients who get better, it may be the laying down of "new grass" that actually protects them for a while. It doesn't last forever. I have a handful of patients who feel better for a year or two, but most patients feel better for just a few months. Nevertheless, it can give a few months of feeling better after not feeling well for quite a long time.
That brings us to treatment. Luckily the FDA has recently approved an oral medication called Elmiron. The hydrodistention can be therapeutic in a number of patients. We are using oral therapy first instead of first trying intravesical (in the bladder) therapy. Elmiron is pentosan polysulfate sodium. The FDA approved dosage range is 100 mg three times a day. We are now experimenting with higher doses of Elmiron. We are studying 300 mg a day (standard dosage), 600 mg a day, and 900 mg a day because it makes sense that a higher dosage may work faster and better. The study is not finished so we have no data yet. The initial studies showed that after 3 months, Elmiron had a 38% success rate. There have been other studies that showed a higher success rate. We used to stop it after three months if people were not responding. Then we learned that if you give it a few more months, you can get more patients to respond. Most of us are advising that if you haven't tried Elmiron for 6 months, you haven't given it enough time. It is worthwhile to be on this medication for 6 months before giving up. In my experience, in a majority of patients on the drug, the results are not subtle. When people respond to Elmiron, they often respond in a big way and it can change their life dramatically. In talking about side effects, if you look in the Physicians' Desk Reference® under any drug, they will have many of the same side effects. One that I will mention is a 3-4% chance of hair loss. The good news is that if it happens, it will occur within the first six weeks, so if you get through this period, you are probably home free. If you are one of those people who has this side effect, by discontinuing the medication, the hair grows back.
Another type of drug we often use with multimodal therapy (using more than one therapy) is an antihistamine (Vistaril®/Atarax®) for those patients with high mast cell counts on bladder biopsy. Also, if someone has tremendous urgency, we might utilize anticholinergic agents. There is a new drug in this class called Ditropan XL®. I am sure many of you recognize the Ditropan® name. The XL is a new formulation. This drug is taken once a day instead of 3-4 times a day, as in regular Ditropan. It works as well as conventional Ditropan with a slightly less incidence of side effects, such as dry mouth. When you take the drug three times a day you get big absorption spikes with side effects. When you take the time-released formula, you don't get the spikes of high levels of the drugs.
We often use tricyclic antidepressants. These are good to modulate central recognition of pain, which is associated with serotonin and norepinephrine pathways in the brainstem. They don't get rid of the pain, but if you imagine pain as a radio, they turn the volume down. The benzodiazepines I use in my practice are Ativan® and Valium®. We sometimes use those in patients who have PFD in addition to IC. For spasm of the pelvic floor muscles, use of a striated muscle relaxant like Valium or Ativan will often decrease the spasms. DMSO deserves mention. We are using it less often. In some cases, patients have had a hydrodistention and are miserable. DMSO is given by catheter into the bladder. I know many people have had bad experiences with it. I think that is because the beneficial effects of DMSO will not kick in until around the 5th treatment. It will often make symptoms worse for the first week or two. DMSO causes the mast cells to "dump" the histamine. Eventually you will deplete the mast cells of histamine. This is one of the ways that DMSO works.
I will now address physical therapy and biofeedback. We use our pelvic floor rehabilitation program for many things having to do with bladder pain and bladder symptoms. IC tops the list. We have been more successful treating vulvodynia with our biofeedback program than IC. It is FDA approved and the Medicare governing board has mandated that before surgery is recommended for urinary incontinence, patients should be put through trials of biofeedback and physical therapy. This is something that is becoming more recognized as reasonable medical therapy. This is the EMG biofeedback machine I use. We try to teach patients how to relax their pelvic floor muscles.
Another new exciting treatment is the Interstim® pain control system. It is a "bladder pacemaker." It is now approved for use in patients with recalcitrant urinary urgency. We are also using it for patients with IC who have urgency and pain. It is an interesting technology. It involves dropping a lead wire into the sacral spinal foramen at the S3 level, which comes in contact with the sacral nerve roots. This modulates down the impulses going to the bladder. I think it is early in this treatment protocol to make predictions. It is technology that is fascinating and I think we are a long way from clearly understanding what we are doing and what frequencies to use, but this is something we need to keep on top of.
I think the most important thing that your doctors need to understand (and this took me a long time) is the "Patients' Rules of IC." If your doctors understand these rules, you will have a much easier time dealing with them. Of course, these are meant to be taken in jest!
Q: You mentioned there is a defect in the lining of the IC bladder. Elmiron seems to help a lot of people. If a patient has taken Elmiron over a long period of time and this has not helped them, do you think the etiology of IC is different in that patient?
Dr. Kaufman: I don't know the answer to that. It makes sense. My personal belief is that I think a vast majority of patients, if not all, have an epithelial defect as the primary etiology. I don't know why Elmiron doesn't work in all of those patients. It could be that we are using too low a dosage. This is under investigation right now and perhaps we are not treating it for long enough. As in many other disease states, there are cofactors involved. In cancers we know you need to have a number of things happening. In colon cancer you need to have biochemical things in the gut and you also need to have a poor diet. I think in IC there are probably cofactors that we do not understand yet. You have a defective lining, but there is something else we have not identified. Why don't all patients who have recurrent UTIs get IC? There is obviously something that happens to IC patients that does not happen to others.
Q: I had 15 DMSO treatments and was on Elmiron twice. I was in horrific pain from both. Why did that happen?
Dr. Kaufman: Why don't these treatments help and why do they make you worse sometimes? I am happy to say that doesn't happen to too many people. Worst case scenario is that Elmiron does not work. As far as DMSO, I have explained why it will sometimes make you worse in the beginning. Perhaps some patients who never get better and continue to feel bad might have a greater quantity of mast cells and we are not getting the histamines out of their systems.
Q: If Elmiron doesn't work well the first time, is it a good idea to try it again?
Dr. Kaufman: I suggested that if you have been on Elmiron at a 300 mg a day dosage and it did not work, you might want to consider getting in the study to try to get a higher dosage.
Q: Does burning have more to do with pelvic floor dysfunction?
Dr. Kaufman: Unless you have urethral infection, which most patients with IC don't have, burning is referred pain; it is a sign of inflammation elsewhere in the lower urinary system and your brain is perceiving it at the urethral level. When we examine the urethra, it looks normal. It could mean we are dealing with pelvic floor dysfunction or bladder inflammation that has not resolved.
Q: What effect does estrogen replacement therapy have on IC?
Dr. Kaufman: I don't know that estrogen therapy has a role in the treatment of IC. Can estrogen build up the urethral musculature and perivaginal tissues? Yes, it can. Gynecologists use this to treat pelvic prolapse and mild stress incontinence. At times it helps in mild cases. I have not been impressed with estrogen therapy and IC. In one of my slides I mentioned that IC pain is modulated by hormone levels in women, so I suggest that if a woman is taking birth control pills and she is in pain, she may go off the pills to see if that helps. If she is not on birth control pills, I suggest that she try that to see if it helps. Sometimes that makes a difference.
Long Island Jewish Hospital
April 22, 2001
Our next speaker is Dr. David Kaufman. Dr. Kaufman is Assistant Professor of Clinical Urology at Columbia College of Physicians and Surgeons and an attending urologist at St. Luke's Roosevelt Hospital, as well as Columbia Presbyterian Medical Center. He is also an ICA Medical Advisory Board member as well as an expert in treating interstitial cystitis. He has particular expertise in pelvic floor dysfunction, which he will be speaking to us about today as well as the etiology of IC.
Good afternoon everybody! I woke up this morning in Orlando, lectured to a group of urologists about IC, and then flew to NY to come speak with you this afternoon! I'm very happy to be here and I thank Dr. Ratner and the ICA for inviting me. It is always wonderful to be speaking with my esteemed colleagues, Dr. Moldwin and Dr. Whitmore.
We will talk today about the etiology of interstitial cystitis. We know that the disease process begins in the bladder with epithelial damage. (slide) This shows the GAG layer of the bladder. Although there are numerous theories about what causes IC, we all agree that there is probably more than just one thing going on. The theory that makes the most sense to me, and we believe accounts for at least 75% of IC cases, involves damage to the GAG layer.
I would like to explain how we came up with the idea of a GAG layer problem. (slide) Here is a look at bladder permeability. Urea (the final product of the decomposition and utilization of proteins in the body. It is eliminated through the urine) can be measured very easily in the bloodstream. If we put urea into an IC patient's bladder, it is absorbed into the bloodstream. In a normal bladder, very little urea would come through, because there is a normal GAG layer, which prevents the urea from being absorbed by the bloodstream. When we treat a normal control bladder with protamine (a chemical detergent that destroys the GAG layer), we are basically creating an experimental IC bladder. Dr. Lowell Parsons performed a study in 1990 that suggested that IC had something to do with damage to the lining of the bladder. There were nonbelievers in the urologic community, then and even now. There was recently an article that tried to disprove the GAG layer theory. In fact, they did the opposite, they proved it all over again. They took another substance, a sugar called rhamnose, which can be measured in the bloodstream. This is a sugar that doesn't occur in the normal foods that we eat. Rhamnose was put in IC bladders and then measured in the bloodstream. The rhamnose was measured in high quantities in the bloodstream of IC patients, but is not found in bladders of normal control patients.
In 1998, we started to become interested in potassium. Potassium is an important participant In the inflammatory cascade caused by IC. (slide) In the potassium stimulation test (potassium is instilled into the bladder) in a normal bladder, very little potassium was absorbed. When you put protamine into the normal bladder, the GAG layer is destroyed and high levels of potassium are measured in the blood stream. When you treat the patient with heparin instilled into the bladder, the potassium absorption goes down. You may be thinking, "This is all about blood tests and potassium levels, but my life is all about pain, frequency and urgency." The same study was done with those parameters in mind. In another potassium stimulation test, instead of measuring the potassium, we asked the patients what they were feeling when the potassium was put into the bladder. Before the potassium was instilled into normal bladders, they had very little urgency and pain. When the protamine was put into the bladder, they developed IC symptoms. We then treated those patients with heparin and the pain and urgency scale went down. These are all sophisticated studies that we used to convince our colleagues that there is science to this whole idea of GAG layer damage in IC.
It is not only your bladder that behaves this way. There are other conditions in the bladder that are also KCl (potassium) positive. There is a condition similar to IC in people who have had too much radiation therapy to their bladder which also shows a positive response to the KCl test. In men with prostate enlargement, who suffer no pain or urgency related to bladder disease, the KCl test is negative.
The proposed pathophysiology of interstitial cystitis includes: a urothelial permeability dysfunction, GAG layer deficit, potassium gets into the cells and irritates nerve endings, causes activation of mast cells, secretion of inflammatory mediators such as histamine, resulting in an ongoing inflammatory cascade. If you have GAG layer damage as seen in IC, potassium from foods you have eaten can go through the interstitium of the bladder and cause these responses. It stimulates the potassium to depolarize nerve endings. The secretions from those nerve endings, which are in the bladder wall, secrete neuropeptides and neurotransmitters, like substance P. We can measure these to show that they occur in higher proportions than in normal patients. These act on other cells in the bladder wall, like mast cells, which contain histamine. This causes the mast cells to secrete histamine, which further stimulates the nerve endings, and this becomes a vicious cycle. This is what causes at least the bladder symptoms associated with IC.
This is a bladder biopsy of an IC patient. This is an electron microscopic view, which is not done routinely. Here is a mast cell, with black histamine granules. Very often when we do biopsies, we ask the pathologist to stain for mast cells. The mast cells often degranulate from the trauma of the cystoscopy and biopsy, which can cause the mast cells to dump histamine. Thus, the pathologist may not be able to find mast cells. See these empty white vacuoles? That is where the histamine was.
There are other things being secreted besides histamine. Leukotrienes are being absorbed by the blood vessels. Heparin-like substances are secreted that stimulate sensory nerves. Substance P is also secreted. This is how we understand the etiology of IC, using the mast cell, or epithelial dysfunction theory.
Many of these neurotransmitters are measurable. We do measure higher levels of norepinephrine, nerve growth factor, substance P and NK-1 in the urine of IC patients. That is just further evidence that what I have just proposed to you is really going on.
I would now like to try to get you off the path of going into the cave, where it says, "Abandon all hope, ye who enter here." We don't want you to abandon hope, because we have a lot of answers. I am going to talk about two end-stages of IC; that is, the patient who has severe bladder pain that isn't manageable with Tylenol, VioxxÆ, CelebrexÆ or Elmiron. I will then talk about a more advanced stage of IC, which I call mature, or advanced IC, which involves the development of pelvic floor dysfunction along with interstitial cystitis.
When we talk about pain, the first line therapy for bladder and pelvic floor pain are the tricyclic antidepressants. I am always very careful when I suggest going on an antidepressant to my patients, because their first notion is that I think they are crazy and they need an antidepressant. The dosages of antidepressants that we use for the treatment of pain are miniscule compared to what the psychiatrists use for the treatment of depression. When psychiatrists used ElavilÆ, the average dose was 300 mg a day. We start with 10 mg and rarely go above 25 mg. The low dosages operate at the level of the spinal cord and probably the brainstem. Although it doesn't take away your pain, it behaves like a radio volume knob; turn that knob to the left, you still have the pain but you don't feel it as much. Many of the side effects associated with the tricyclics are ones that we welcome. We want Elavil to give us antihistamine side effects, we want Elavil to have a soporific effect to make you sleepy. Elavil has been on the market for a long time and there have not been any studies, but we do know it works and it can be first line therapy for pain with IC.
There is a new class of medications, called neuroleptics. This includes NeurontinÆ. Neurontin, as well as DilantinÆ and TegretolÆ were developed for the treatment of epilepsy. The anesthesiologists who treat chronic pain discovered that they work well in the treatment of neuropathic pain, which is what IC patients have. We start with 300 mg three times a day of Neurontin, and go up to 900 mg three times a day, and sometimes higher. I was at an IC support group a few years ago and a patient said that Neurontin was the only drug that had made a difference in his life.
Sometimes we have to use narcotics. Many of you have heard Dr. Brookoff speak, and he has convinced me and other urologists that you need to treat the pain of IC. If you have to give narcotics, then you do that. People who have chronic pain do not become addicted to narcotics. They need the narcotics to function normally. We like to start with Vioxx and Celebrex, which are non-narcotic antiinflammatory agents. If these don't work we then use TylenolÆ with codeine or PercocetÆ and finally, OxyContinÆ, which is sustained-release morphine. This drug needs to be used carefully, but it is an excellent drug that gives pain relief, and you only have to take it twice a day. In my practice, if OxyContin is not holding my patients, I send them to the pain center at Roosevelt Hospital.
I would like to talk about pelvic floor dysfunction (PFD). PFD is something that we see in IC in the advanced or "mature" forms. Although I don't have numbers, in my experience, it takes at least two years for an IC bladder to evolve into an IC bladder with pelvic floor spasms. In a very advanced case of IC, there is also damage to the nerves that cause spasm and dysfunction of the pelvic floor muscles. (slide) This shows how intimately related the bladder is to the pelvic floor muscles. The sensory and afferent nerves from the bladder return to the spinal cord, where they share nerve roots with the same nerves that go down to the pelvic floor muscles; the levator and pubococcygeal muscles. When these nerves are stimulated by IC or "up-regulated", there is some transference of activity, and the nerves that these are attached to that send signals to other places, also get up-regulated. That is how PFD occurs. When Dr. Lowell Parsons speaks to doctors, his favorite phrase is, "It's the bladder, stupid." We try very hard to convince the urologists that IC is a bladder disease. I feel it may be a little more than just the bladder and it may involve the pelvic organs and the pelvic muscles surrounding the bladder as well. With chronic bladder inflammation from IC there is a "reawakening" of these aberrant nerve endings that go to the pelvic muscles around the bladder and cause those muscles to go into spasm. That is what PFD is all about; abnormal spasm of the pelvic floor muscles associated with chronic inflammation of the bladder and prostate. Men who have chronic inflammation of the prostate can have PFD.
We also find a similar situation in vulvodynia and vulvar vestibulitis, which is a "cousin" disease to IC, in female patients. Up-regulation of the nerves that go to the vagina also feed back on the nerves to the pelvic floor and cause PFD as well.
To summarize, some of the conditions we see associated with PFD are: IC, vulvodynia and vulvar vestibulitis and chronic pelvic pain syndrome, which is a new catchword for IC in men.
I may be on somewhat thin ice right now, but I have seen in my practice that patients who have had recurrent urinary tract infections (UTI) that are documented by positive cultures could also, over time, develop spasm of the pelvic floor muscles. That supports the notion that inflammation (doesn't have to be IC) of the bladder can irritate the pelvic floor muscles as well. The symptoms of PFD are: urinary urgency and frequency, chronic pelvic pain, dyspareunia (pain with intercourse), low back pain, dysfunctional voiding, constipation and, in men, ejaculatory discomfort. These are hard to separate from IC but at times, they can be caused by PFD.
When I give this talk to urologists, I spend a lot of time teaching them how to examine the patient. I tell them how to rule out vaginal infections, vulvodynia, and urethral diverticuli. I then teach them how to evaluate for IC. To very gently, move the examining finger against the anterior vaginal vault along the urethra, until they are just underneath the bladder base. To gently lift up on the bladder base. Unfortunately when we do that to an IC bladder, it can hurt quite a bit. When you do that to a bladder with a UTI, it bothers the patient, but it is nowhere near the kind of reaction we get in an IC patient. The next step is to evaluate for the presence of PFD. They put their finger up against the floor of the bladder and rotate the finger laterally to feel the muscles of the pelvic floor. If they move their finger to a 3 o'clock position laterally, they will feel the levator ani muscle going straight up and down, almost like a guitar string. Very gently, they are to press on that muscle or strum it as if it were a guitar string. In a patient with PFD, there will be an extremely dramatic response to that exam, often more than occurred when we felt their bladder. That is a good indication that we are dealing with more than just IC, we are dealing with mature IC, or IC with PFD. Obviously you can do that same exam in a man, through the rectum. Instead of swinging down, you swing the finger up to feel the same muscles. The more we look for PFD in men, the more we find it. It is present more often than we ever imagined.
How is PFD treated? We start with skeletal muscle relaxants. ValiumÆ or AtivanÆ can be used. These are benzodiazepines that relax the muscles that are in spasm in PFD.
Biofeedback, electrical stimulation, body work and massage therapy can also be used. I work closely with a therapist who does Hellerwork. This allows her to get into the muscles with massage therapy and does trigger point therapy as well as myofascial release. Dr. Whitmore uses a physical therapist who does intravaginal massage and trigger point release. There are a lot of ways to get to these muscles that are in spasm.
Biofeedback is not a treatment, it is an education! We teach the patients to find the muscles that are in spasm in their own body, and how to relax those muscles. You are not necessarily going to feel better after biofeedback, you will feel better when you do the exercises. Biofeedback is used for many things; IC, vulvodynia, frequency and urgency without IC, urge incontinence, stress incontinence, and PFD from prostatitis. There are biofeedback units for the office and for home use. I utilize an EMG vaginal probe. There are two silver rings around it that measure muscle activity. For men, we have a smaller rectal probe. For women who have trouble accommodating the probe, there are smaller tampon-size probes. The purpose of biofeedback is to teach identification and isolation of the pelvic floor muscles. Patients are taught contraction and relaxation exercises, which are a variant of Kegel exercises, but with an emphasis on relaxation. We are not trying to stop incontinence, we are trying to teach you to relax the muscles. By doing these kinds of exercises with my biofeedback therapist, you eventually learn how to find these muscles without looking at a computer screen and how to do the relaxation on your own. Once we teach the patients biofeedback, to find the muscles and relax them, they can rent a home device that does electrical stimulation at home.
I am a solo practitioner in New York City, but I use resources that are available to me: physical therapists, massage therapists, biofeedback therapists, acupuncturists, and pain management. This is a multidisciplinary team approach to this very devastating problem that so many of you suffer from.
Q: Is there a treatment of the GAG layer to correct the etiology of the problem rather than treat the symptoms?
Dr. Kaufman: There is no better treatment of the GAG layer than Elmiron. Elmiron was created to repair the GAG layer. I think what you mean is, does that really fix the problem. It does, as long as you keep taking the Elmiron. The big question is, do you need to take Elmiron forever? We don't know the answer to that. Anecdotally, some of the patients who I have treated 10-12 years ago who were taking Elmiron before it was FDA approved are feeling fine and no longer taking Elmiron. From a 10 year perspective, it is possible that we can fix the bladder and no longer need the medication.
Dr. Ratner: What about the people who do not respond to Elmiron?
Dr. Kaufman: I think people who do not respond to Elmiron probably don't have an epithelial deficit. They would probably have a negative KCl stimulation test, so they need different therapy.
Q: Can Elmiron be instilled into the bladder?
Dr. Kaufman: Yes, but if you are ready to put a catheter into your bladder, don't use Elmiron because it is very expensive. Use heparin. Elmiron is just an oral analogue to heparin. We were looking for something that acted as well as heparin, and this is Elmiron. Heparin already comes in liquid form and it is perfectly suited to put in the bladder. Heparin was used in the bladder before Elmiron was in use.
Q: What happens during pregnancy?
Dr. Kaufman: Those patients I mentioned who are not taking Elmiron stopped it because they wanted to get pregnant. There has not been research about the effect of Elmiron on the fetus, so I don't feel you should take it if you are pregnant. The ICA has literature on IC and pregnancy. If you are breast-feeding, you shouldn't take Elmiron. You can go back on Elmiron when you are finished breast-feeding. If they have felt well while off the Elmiron, they will take Elmiron once a day or every other day. They can then wean themselves off Elmiron, if they are feeling well enough.
Q: Will DMSO remove the GAG layer or slow down Elmiron therapy?
Dr. Kaufman: We actually use DMSO therapy in many patients who are beginning Elmiron. Since Elmiron may take 3-6 months to start, we will often use a DMSO cocktail, which will give most patients relief. Often, by the 3rd or 4th instillation, there are significant improvements. Patients stay on the DMSO until we feel that the Elmiron is starting to work. DMSO does not destroy the lining. DMSO is an organic solvent, it penetrates through the GAG layer, it has antiinflammatory effects, it is a mast cell destabilizer, causing the mast cells to dump their histamine. That is why people can feel worse after the first few treatments, because it rids the bladder of histamine. After the first or second treatment, depleting the bladder cells of histamine is a benefit, because it gets the histamine out of the inflammatory cascade.
Q: What exercises are contraindicated for pelvic floor dysfunction? For example, jogging.
Dr. Kaufman: I think the bottom line is, anything that hurts is contraindicated. One of my patients told me that she was miserable all the time, except when she was at the gym. She used an abductor/adductor machine. This exercises the pelvic floor muscles. If you use the muscles the right way, the way they are supposed to move, it forces them to snap out of spasm. Exercise is an important part of treating pelvic floor dysfunction. Our therapists and biofeedback technicians do biofeedback, but they also teach patients what kind of exercises they need to do to get the muscles working the right way.
Q: Are there alternative therapies available in Europe that are not yet in the U.S.?
Dr. Kaufman: Resiniferatoxin was under study in Italy. It is a very strong form of capsaicin, but does not produce the pain that capsaicin does. Hopefully we will see more of these things in a few years.
Q: I have IC, vulvodynia and spinal stenosis. Are there tests which can be done to determine if the leg pains are coming from the spine, IC or from the pelvic floor?
Dr. Kaufman: An easy to find out if it has anything to do with the IC is to do a KCl stimulation test. If putting KCl in your bladder causes the lower extremity pain, then it is from IC. If you just have pain in the bladder and it doesn't mimic the lower extremity pain, it is probably not the bladder. If you do a pelvic floor exam and that reproduces the pain in the lower extremities, then it is probably related to the pelvic floor dysfunction. If none of those things mimic the pain, it is probably from spinal stenosis.
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