23 – August 27, 2010
August the ICA and the Pelvic and Sexual Health Institute (PSHI) presented the
findings of the ICA Complementary and Alternative Medicine survey at the joint
meeting of the International Continence Society and the International Urogynecological
Association in Toronto.
IC studies at this meeting were numerous but many were available only as abstracts to be read. That is likely a reflection of urogynecology practice today, which is focused mainly on surgery for incontinence and prolapse, so we need to work hard to educate urogynecologists about IC and its treatment.
Many of the IC studies here were on research we've already
reported on for you about sacral neuromodulation, botulinum toxin (Botox)
injection in the bladder, steroid injections into Hunner's lesions, and oral
dextroamphetamine. Nevertheless, there was also new and intriguing IC research.
CAM Use Among IC Patients
poster was based on the results of the ICA’s 2009 Complementary and Alternative
Medicine (CAM) Survey and statistical
analysis and perspective from ICA Medical Advisory Board member Kristene
Whitmore, MD, nurse practitioner Amy Rejba Hoffmann, CRNP, and statistician
Anand Bhattacharya from Drexel University in Philadelphia.
survey proved to be the largest ever of IC patients presented in a scientific
study. You read about the overall survey results in the Summer 2009 issue of
ICA Update. But for this poster
session, we analyzed only the answers from the 1,982 respondents who said they
had a definite IC diagnosis to help us zero in on therapies that might really
have an effect on IC. Then, we applied statistics to determine which therapies
a statistically significant number of IC patients thought were helpful and which
weren’t. What’s more, statistics helped us look at the differences in what
helped IC patients who had been diagnosed a short time ago compared with those
who had had IC for a long time.
analysis confirmed some things you already know but also produced some
surprises. The CAM therapies that you said work best include heat or cold,
diet, many mind-body techniques that are now used in pain management, and a few
those supplements included only one we knew to be popular among IC patients,
Prelief, and also included probiotics, fish oil, and vitamin D. None of the
herbal therapies made it to the significantly helpful list. Some of the
supplements that fell into the statistical gray area for all the respondents
worked better for those who had had IC for a relatively short time.
surprise the statistics showed us is that, although many of the CAM therapies
work better for those who have not had IC for a long time, many patients diagnosed a
year or less ago have not tried them. Somewhat more than a quarter have not
tried diet or physical therapy, which are recommended in the American
Urological Association’s preliminary IC clinical guidelines, and nearly half
have not tried any other type of CAM therapy.
patients said they had a doctor recommend a therapy, showing that doctors are
interested in CAM, too, but apparently, not enough of them are making the
recommendations early, when CAM therapies, such as diet, seem more likely to
help their patients.
there were therapies that came up unhelpful - that is, a significant number of
patients who tried them thought they didn’t work. That runs counter to the idea
that the placebo effect is so strong that just about anything patients put
their faith in will do something for them.
results show that there is some wisdom of the crowd. You’re not usually swayed
by the hope that something will work, and the most popular “CAM” therapies are
now becoming accepted mainstream treatments. Dietary modification, for
example, has long been popular among IC patients but was not accepted by some
of the medical community until just recently. Of course, this survey can’t
prove what works, but it can help clinicians give patients some helpful
pointers, and it can show which CAM therapies might deserve some more formal
doctors, physical therapists, nurse practitioners, and patient advocates
stopped by the poster to study it, ask questions, and give their feedback. In
fact, one physician in the Multidisciplinary Approach to Pelvic Pain
research network remarked, “This is a good study!” Go to the ICHelp YouTube
channel to view coauthor Hoffmann’s presentation talking about the ICA/PSHI study and how she is using the findings in her practice.
the published report about the survey? Order a back issue of the Summer 2009 ICA
More on CAM – Acupuncture, Honey
Instillations, Hydrogen-Rich Water
intriguing CAM study showed that acupuncture at the sacrum eased symptoms in
rats with irritated bladders. The new study looked into how it might work.
Acupuncture eased bladder muscle spasms and also reduced inflammation in
bladder tissue. Another animal study looked at the potential of honey
instillation (don’t try this at home!) to reduce bladder inflammation and mast
cell activity. Honey seemed to have some protective effect on bladder lining
cells, and it inhibited mast cell degranulation (the process of spilling their
contents, which can result in allergy symptoms, inflammation, and pain). A
controlled, randomized trial tested the effects of “hydrogen-rich” water on IC
patients and found no significant effect, although some patients improved.
IC in Men
Diagnosis of IC in men got some research attention at this meeting. One
group of clinicians reviewed the records of 147 men who underwent cystoscopy
and hydrodistention. Fifty-six percent got an IC diagnosis by “NIDDK criteria.”
The mean lead time to diagnosis was 2.5 years. Although IC is not being
diagnosed today by those old criteria, which treated glomerulations as
diagnostic, men are indeed underdiagnosed. The symptoms that were common in
the men when they came for treatment certainly fit the IC picture: 84
percent had urinary frequency, 63 percent had pain in the bladder area, 61
percent had urgency, 49 percent had bothersome nocturia, and 41 percent had
pelvic floor pain. In addition, 74 percent had painful urination, 51 percent
had testicular or penile pain, 26 percent had “chronic pelvic pain syndrome,”
24 percent had benign prostate enlargement, and 41 percent had urinary tract infections.
Like women with IC, most of the men (81 percent) had conditions often
associated with IC. Forty-one percent had gastrointestinal complaints, 37
percent had anxiety or depression, 34 percent had chronic back pain, 23 percent
had chronic joint pain or neuropathy, and 9 percent had migraines.
What Might Cause IC, New
A number of studies were aimed at uncovering what might cause IC and new
ways of diagnosing it. One used a very new technique to look in urine for tiny
amounts of the genetic material RNA related to genes that are more active in IC
patients than in healthy people. The team found RNA markers of distinctive gene
expression in IC patients with Hunner’s lesions but not in other IC patients.
On the other hand, another team, which previously identified some 28 micro RNAs
that were different in IC patients than in controls, zeroed in on one micro RNA
called miR-199a-5p. This micro RNA seems to play a role in how “tight” bladder
lining cells are and may be the key to the “leakiness” of the bladder lining,
thought to be a characteristic of IC. Another study of the workings of the IC
bladder lining linked inflammation under the lining, high rates of bladder
lining cell death, and low levels of proteins that bind the cells together and
help form the barrier. One protein in particular, E-cadherin, was low in IC
patients, and low levels correlated with pain scores.
The concept of phenotyping has been
talked about a lot lately in IC, and one study here introduced a new IC
phenotyping approach. It
characterized IC patients by their degree of pain, looking at the differences
between those with mild to moderate pain (pain scores from 0 to 7) and those
with severe pain (scores greater than 7). Patients with the lower pain scores
tended not to attribute their IC to any specific cause. Those with higher pain
scores could often attribute the onset of their symptoms to an acute bladder
infection or to surgery or trauma to the pelvic area. Patients with severe pain
were less likely to have benefitted from hydrodistention, and had more problems
with voiding, rather than urine storage than those with less pain. IC also had
a greater impact on the ability to work in patients with high pain scores. It
may be that when some severe event kicks off IC, it stimulates local or
regional pain pathways in a big way, which carries forward in the degree of
One treatment study looked at sacral neuromodulation
in a way that has never been done before. It analyzed how irritable bowel
syndrome (IBS) occurring with IC affected the treatment’s outcome. The
researchers looked at the records of 79 IC patients who tried sacral
neuromodulation, 25 of whom also had IBS. The IC patients with IBS had more
pain at the outset, and outcomes of treatment were not as good when patients
had IBS or higher pain levels to begin with. Over the long term, patients
without IBS maintained a better response to treatment than those with IBS, and
more patients with IBS had the implants removed.
Steroids for Hunner’s Ulcers
and Urethral Pain Syndrome
revived an abandoned IC treatment, oral steroids, in a new context - just for IC
with Hunner’s lesions. The patients had already had their lesions
excised or fulgurated (“burned off”) from one to seven times, but their symptoms
came back. They took the steroid betamethasone orally at a higher dose for one
or two months, and then at lower doses for an average of nearly a year. Twelve
of the 23 patients improved, and 2 were able to stop taking the steroid.
Although the treatment needs further study, it could be an option for this
severest form of IC, said the authors.
Although not about IC specifically, a study of treatment for “urethral
pain syndrome” may be helpful for the IC patients who do have urethral pain
with urination. The clinicians put a combination of a potent steroid
and lidocaine gel in patients’ urethras once or twice a week for the first week
and then once a week thereafter. Some patients got as many as 16 treatments,
but the average was 2. The authors said that 60 percent of the patients were
cured and the rest were improved.
Basic Research Points to New Treatments
Basic research pointed to some potential new treatments. In one study,
researchers who have been working with a virus to inject helpful genes into
bladder tissue are now looking at that possibility with an immune system
signaling protein IL-4, which has anti-inflammatory effects. IL-4 has too many
side effects to be a systemic (whole-body) drug, but it could help if it were
targeted to the bladder. The researchers found that, in rats with irritated
bladders, treating the bladder with the IL-4-gene containing virus eased
bladder overactivity and pain. Another study tested a potential drug that
blocks a purinergic receptor, that is, receptors that ATP attaches to. ATP is
important in transmitting bladder pain signals, as our readers have been
hearing about for some time. Now, a small-molecule compound, AF-742, which
targets this receptor, is showing potential. It blocked activation of these
receptors in nerves and calmed spasms in irritated rat bladders.
Pudendal Neuropathy and Pelvic
Floor Dysfunction and Pain
workshops at the meeting helped clinicians lean to understand and treat IC and
some of its associated conditions. Sometimes, contend some pelvic pain experts,
pudendal neuropathy or damage to the pudendal nerve can be mistaken for
IC and chronic prostatitis/chronic pelvic pain syndrome, and sometimes,
it may coexist with these conditions. The workshop “Pudendal Neuropathy and Its
Pivotal Role in Pelvic Floor Dysfunction and Pain” helped clinicians learn how
to diagnose and treat this condition. Treatments range from self care to physical
therapy, nerve blocks, and surgery in severe cases. Learn
more about this topic:
the meeting webcast. Click on “Workshops” and then
interview with physical therapist Stephanie Prendergast, MPT on the ICHelp YouTube
channel, who is known for her work in treating pudendal neuropathy with
physical therapy. Also check out our interview with Prendergast in the Summer
2009 ICA Update.
Is it Mind? Is it Bladder?
for the workshop, “Is it mind? Is it body? Is it bladder? Is it real?” included
ICA Medical Advisory Board members Ragi Doggweiler, MD, Dr.
Whitmore, and Fred Howard, MD, as well as gastroenterologist Alan
Watier, MD. Both mind and body play important roles in pelvic pain, according
to workshop leader Dr. Doggweiler. For IBS, the
most effective therapy is a mind-body therapy, hypnosis, according to Dr.
IC patients, who in the past were often only referred for psychiatric therapy because
so many physicians saw IC as just a psychologic problem, Dr. Howard’s perspective
was helpful. He discussed a telling study of treatment for another pelvic pain
condition, pelvic congestion syndrome. In this study, patients got a progestin as
medical therapy, progestin plus psychiatric treatment, placebo, and placebo
plus psychiatric treatment. Placebo and placebo plus psychiatric treatment had
little effect. It took medical therapy for patients to get better. After four
months, medical treatment and medical treatment plus psychiatric treatment had
the same effect. But interestingly, after 13 months of treatment, those who got
psychiatric support along with the medical therapy did better than those who
got medical treatment alone.
Whitmore emphasized the importance of multimodal therapy in IC, aimed at
treating all the sources of pain. One of the new ideas in the field,
phenotyping, should help guide clinicians to do that, since it takes the
associated conditions into account and helps clinicians identify the pain
and symptom generators. Dr. Whitmore also discussed some of the newest
approaches to treatment, including injections of botulinum toxin (Botox)
into the pelvic floor, and her take on how to treat the worst cases of IC. You
can hear what she has to say about that, how IC therapy has progressed in the
last 10 years, and what she sees on the horizon for IC on the ICHelp YouTube
Posted September 13, 2010