Peyronie's Disease - the blog

Xiaflex - one more step towards use with Peyronie's

2010-03-16T18:20:00.000-07:00

Years away for use with penile fibrosis, but still worth following...

Triumph for Xiaflex, Drug to Straighten Clenched Fingers - NYTimes.com

... The Food and Drug Administration approved ... Xiaflex, last month as a nonsurgical treatment for Dupuytren’s contracture, a condition in which one or more fingers cannot be straightened.

Xiaflex, an injectable drug that goes on sale later this month, will not be cheap, at an estimated average cost per course of treatment of $5,400. But analysts expect sales to reach hundreds of millions of dollars a year.

And that total could go higher, if Xiaflex eventually wins approval for a related condition known as Peyronie’s disease, in which a bent penis makes intercourse painful or even impossible.

About one in 20 men is estimated to have Peyronie’s, but figures are not precise because people with the condition tend not to discuss it publicly...

... Some people treated with Xiaflex in clinical trials for the Dupuytren’s hand condition said it had made a big difference in their lives, and had allowed them to avoid painful surgery.

“When I looked down and saw my finger straightened out, I cried,” said Kenneth Nelson, 65, of Indianapolis. “It was to me just like a miracle.”

Xiaflex is an enzyme produced by a gangrene-causing bacterium, Clostridium histolyticum, which uses it to eat away the tissues of its victims. The enzyme, called collagenase, breaks down collagen, a major component of the body’s connective tissue that is found in skin, tendons, cartilage and other organs.

But collagenase by itself does not cause gangrene. And there are times doctors need to break down collagen, such as when an excess builds up in the hand or penis, causing Dupuytren’s and Peyronie’s. The ailments are named for French surgeons who described the conditions in the 18th and 19th centuries...

... Auxilium sought approval for treating Dupuytren’s first because it was easier to measure success in straightening fingers. But the company hopes to begin late-stage trials of Xiaflex for Peyronie’s disease later this year. In a midstage trial, injections of Xiaflex into the collagen plaque in the penis reduced the curvature. But the drug did not reduce pain or discomfort during intercourse by a statistically significant amount.

While collagenase itself is not patented, the companies do have patents on the use of the enzyme to treat Dupuytren’s and Peyronie’s. They are also shielded from competition for seven years under a federal law aimed at spurring development of drugs for rare, or “orphan,” diseases — even though newer estimates suggest these two diseases are not as rare as thought when the drugs were given orphan status...

This has been discussed for some time, so this is more of a milestone than major news. My suspicion is that if it does work at all, it will work best for persons early in the disease. Penile fibrosis appears to destroy tissues that will not regenerate, so even clearing the fibrosis does not mean restoring function.

Apologies for missing real comments

2009-06-19T20:25:00.001-07:00

Most the comments I get on this blog are spam, typically for mail order viagra. I did miss several quite valid comments though, and I've just fished them out.

The blog obviously hasn't been very active. This is not because my fairly severe Peyronies has gotten any better. I don't think that's going to happen. It's mostly because my life is generally full of things that are either good or very demanding, and because there really isn't much new to say about this disorder.

I will try to catch up a bit more though.

Review of medical treament - nothing new

2008-11-02T10:54:00.001-08:00

I've not added much to my blog posts because very little is happening with the understanding or management of Peyronie's Disease. I try to post when I find something novel.

This article doesn't have anything new, but it's a good summary of the urologist's current medical approach (emphasis mine and I've reformatted for readability):

Medical Management of Peyronie's Disease. [J Androl. 2008] - PubMed Result

Peyronie's disease (PD) is a wound healing disorder in which a fibrotic plaque forms in the tunica albuginea layer of the penis. It clinically presents as any combination of penile pain, angulation, and erectile dysfunction (ED).

Recent studies indicate that PD has prevalence of 3-9% in adult men.

While the exact etiology has not been established, PD likely results from a predisposing genetic susceptibility combined with an inciting event such as microtrauma during intercourse. During the initial acute phase (6-18 months), the condition may progress, stabilize, or regress.

For this reason authorities recommend a more conservative treatment approach with a trial of oral and/or intralesional pharmacotherapy before surgical reconstruction is considered.

Oral therapies most commonly employed include tocopherol (vitamin E), and para-aminobenzoate (Potaba), with colchicine, tamoxifen, propoleum and acetyl-L-carnitine being used less often. There are a limited number of long-term placebo- controlled studies with these oral agents and for the most part, studies have failed to show a consistent beneficial effect.

Intralesional injection therapy for PD is more commonly being used as a first line therapy. The current standard of care includes injection with interferon-alpha-2b, verapamil, or collagenase.

Interferon-alpha-2b, in particular, has been documented in a large, multicenter, placebo-controlled study to show significant benefit over placebo in decreasing penile curvature, plaque size, penile pain, and plaque density.

However, intralesional interferon is associated with post treatment flu-like symptoms unless premedicated with a non-steroid anti-inflammatory agent. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids, orgotein, radiation, and extracorporeal shockwave therapy (ESWT).

Surgery is considered when PD men do not respond to conservative or medical therapy for approximately 1 year and cannot perform satisfactory sexual intercourse...

Translating from the jargon I'd summarize this as:

Most treatments have been shown not to work and should be abandoned.
Interferon-alpha-2b injection may be worth trying in the acute phase, but be ready for side-effects. I'd recommend asking for an explanation of exactly how much improvement was found, and whether the improvement was age group specific. Interferon injections have been proposed for many problems and they are usually found to be ineffective. This would be more persuasive if there were solid physiologic reasons to think it should work.
The "wound healing" explanation is not confirmed. I suspect the cause varies with age of onset, and that there may be a common predisposition both to injury and to dysfunctional healing.

The article does not address how well surgery works, it's a medical review. Long term surgical outcomes have been mixed at best.

The take away is to consider the interferon but cautiously. We haven't learned all that much about Peyronie's in the past 10 years, but at maybe we're using fewer ineffective treatments.

Dupuytren disorders site and Peyronie's disease (IPP)

2008-03-05T05:49:00.000-08:00

A comment by Wolfgang on a prior post pointed to a web site on Dupuytren's disorder, which included this page - Diseases related to Dupuytren: Peyronie's disease (IPP). It's a great resource for persons with Peyronie's and I need to explore it further. On initial inspection it feels pretty evidence-based and very topical.

It's authored by a German scholar, written in English.

Dupuytren e.V.
Westerbuchberg 60b
83236 Übersee
Germany

Responsible for the content of this site:
Secretary/1. Vorsitzender: Dr. Wolfgang Wach
Dr. Wach is a Dupuytren patient, not a medical doctor.

Vitamin E: not harmless

2008-02-29T16:40:00.000-08:00

Vitamin E is commonly prescribed for Peyronies Disease, even though it has been shown to have NO benefit and even though several studies have suggested that high dose Vitamin E is mildly toxic.

Today another study suggested Vitamin E may slghtly increase lung cancer diagnoses:

Vitamin E Supplements May Raise Lung Cancer Risk - washingtonpost.com...

Our study of supplemental multivitamins, vitamin C, vitamin E and folate did not show any evidence for a decreased risk of lung cancer,' study author Dr. Christopher G. Slatore, a fellow in the division of pulmonary and critical care medicine at the University of Washington, said in a statement...

... Every increase in vitamin E of 100 milligrams per day was associated with a 7 percent rise in lung cancer risk -- translating into a 28 percent increase in risk over 10 years for someone taking 400 milligrams of vitamin E daily....

A 28% increase in lung cancer risk still isn't in the range of second-hand smoke, but it's significant.

Vitamin E is worthless as a Peyronies treatment. It's probably not harmless in large doses.

Urologists should not prescribe it.

Device corporation launches "social networking" site for Peyronie's Disease -- and their "biodesign repair graft".

2008-02-05T20:24:00.001-08:00

Cook Medical is a part of the Cook Group, an oddly diverse multinational (emphases mine):

Since 1963, Cook Group companies have been among the leaders in developing healthcare devices that have improved lives around the world. COOK remains at the forefront of medical research and worldwide sales of products for endovascular therapy, critical care medicine, general surgery, diagnostic and interventional procedures, bioengineered tissue replacement and regeneration, gastroenterology and endoscopy procedures, urology, and obstetrics and gynecology.
Our COOK corporate family also includes companies that manufacture specialized industrial parts and offer commercial services in the travel, real-estate development and management, and retail fields.
COOK is a global company with a global focus - and a global future.

Real estate services and endovascular devices? Now that's weird. I suspect they're privately held, which probably explains their idiosyncratic portfolio.

The medical device company, among other things, sells the Surgisis Biodesign Peyronie's Repair Graft

... The Surgisis Biodesign Peyronie's Repair Graft can help restore a patient's lifestyle and confidence. Surgisis Biodesign provides strength and flexibility for reinforcement and correction of penile curvature. The graft signals the body's surrounding cells to grow across the scaffold, remodeling into functional tissue. Surgisis Biodesign is easy to hydrate and suture, minimizes scar tissue formation, and is resistant to infection....

The Surgisis line appeared on "The History Channel" a few months ago, which leads to some cynical speculation on how that channel is funded. I couldn't find any medical articles referencing this product, a scholar.google.com search had one hit.

Which brings me to Peyronie's - Getting Information and Help. This is billed by Cook Medical as a "social networking site" (from an email I was sent):

... Cook Medical is launching MensHealthPD.com, and leveraging social networking capabilities to create a safe and interactive destination for physicians, patients and their partners to learn about symptoms and treatments, discuss and share thoughts and opinions and have access to the latest information around Peyronie’s disease. Physicians can also engage in a secure, physicians-only Q&A forum to foster knowledge exchange...

Unsurprisingly their therapy reference includes this blurb:

... Plaque Incision or Excision and Grafting: This procedure removes tissue on the inside of the curve and replaces it with a graft to allow the penis to straighten. The graft can either be tissue from the patient or a biological "off-the-shelf" material such as Cook Medical's Surgisis^® Biodesign™ Peyronie's Repair Graft or a cadaveric pericardial graft...

Well.

Ok, so it's a time honored practice in the pharma industry to create "patient friendly" web sites which, oddly enough, slip in some marketing on the side. Even so, this one feels a bit a bit edgy to me. There are NO references to any published research about their "Surgisis Biodesign" graft material, and it's obviously the entire reason the site exists.

If you do visit this site, please remember why it exists.

Urologists - how they treat Peyronies Disease

2007-12-03T19:01:00.000-08:00

Urologists are no more evidence based in their practice than most physicians ...

Urologist Practice Patterns in the Management of P...[J Sex Med. 2007] - PubMed Result

Introduction. Peyronie's disease (PD) is a poorly understood clinical entity. Aim. We endeavored to determine how contemporary urologists in the United States manage PD.

Methods. A randomly generated mailing list of 996 practicing urologists was generated from the American Urologic Association member directory. A specifically designed survey was mailed with a cover letter and a postage-paid return envelope. ...

...Results. Responses were received from 236 (24%) practicing urologists. Vitamin E was the preferred initial management for 70% of respondents, with observation, Potaba (Glenwood, Englewood, New Jersey, USA), colchicine, verapamil injections, and verapamil gel favored by 32, 20, 12, 7, and 10% of respondents, respectively. Fifty-seven percent of respondents performed surgery for PD, with penile prostheses, Nesbit procedure, grafting, and plication used by 76, 66, 55, and 51% of respondents, respectively. Medical therapy and/or observation was the preferred management for all of the cases except case 3, for which penile prosthesis placement and referral were the favored options by 39 and 30% of urologists, respectively...

Vitamin E does nothing and may have some toxicity in high doses. So it's unfortunate that 70% of urologists still use it. On the other hand, I suspect that the number would have been 90% a few years ago, so this probably is progress.

There's a bit more evidence for some other interventions, but none that I'm aware of for Potaba and precious little for cochicine.

Surgery isn't so hot either ...

2007-10-28T16:43:00.001-07:00

I've just posted on another study showing Vitamin E is a waste of money. This article points out at least some surgical techniques aren't so great either.

Long-term patient satisfaction after surgical corr...[Int Braz J Urol. 2007 Jul-Aug] - PubMed Result

...Long-term outcome after surgical correction for PD and CPC with the technique of tunical plication can be poor. Probably patient expectations are above the real performance of surgical techniques...

We simply don't have any effective treatments for established Peyronie's Disease and there are none on the horizon. There's probably more hope in:

early identification of at-risk persons (probably via genomic testing) and inventing and studying preventive measures
focus on interventions for early onset disease in young persons

Vitamin E really, really, really does not do anything

2007-10-28T16:38:00.001-07:00

Yet another in a long line of similar results ...

Comparison of vitamin E and propionyl-L-carnitine,...[J Urol. 2007] - PubMed Result

...This study did not show significant improvement in pain, curvature or plaque size in patients with PD treated with vitamin E, propionyl-L-carnitine, or vitamin E plus propionyl-L-carnitine compared with those treated with placebo...

Vitamin E has some mild toxicity as well, though I can't recall the details at the moment.

Urologists, stop the Vitamin E. Please. It looks silly.

Peyronie's emerges from the closet

2007-09-30T06:48:00.000-07:00

Peyronie's isn't the kind of disorder most people are comfortable complaining about. Dole made impotency somewhat acceptable, but, no presidential type has done that for Peyronie's. Still, the boomers are getting Peyronie's, and the boomer's are good about dragging things out of the closet.

Peter Kurth is a gay man who's been HIV positive since 1981, so he knows something about the world of shameful secrets and dealing with life's indignities. Writing in Salon, he comes out about something more embarrassing than gender preference -- Peyronie's Disease. He also illustrates why it's kind of unfortunate that Peyronie's is "owned" by urologists ...

middle age, crooked penis | Salon Life

... Peyronie's disease, the doctor then told me gently, is also called "partial penile disassembly." It is a condition of "uncertain cause," characterized by plaque, or a hard lump, or scar tissue, that forms in the penis and causes an abnormal curvature when the member is erect. Cases range from mild to severe. Peyronie's isn't "rare," exactly, but it's not "common" either. And it may or may not have anything to do with HIV or the medications.

"It afflicts men mainly in middle age," the urologist shrugged. "The sexual problems that result can disrupt a couple's physical and emotional relationship and lead to lowered self-esteem."

While I was stuck on the phrase "middle age," he carried on: "It's just the roll of the dice for middle-aged men. My guess is your penis has suffered some kind of trauma."

"Oh, Doc, you don't know," I answered, thinking of my whole checkered sexual history. "But the 'trauma' would have to have occurred some time ago, because my penis hasn't suffered anything in about three years."

Apparently there are only a few treatments for it, and my doctor tells me that none of them will work effectively for me. The first line of defense is massive doses of vitamin E, which the doctor can't, in good conscience, give at the levels he would normally prescribe, as vitamin E would contribute to "hepatic toxicity" (liver problems), brought on by the other pills I'm on. The second option is injections of some kind -- needles to the dick -- "which hurt like hell," the urologist said, "and they don't work, either." The third is penile implants, "but who wants a lead weight between his legs?" (I refrained from comedy here -- I knew all too well what he meant.) And the fourth, and most drastic, is surgery. "But I warn you," said the doctor, "you'll lose two or three inches. No more Peyronie's, but no penis, either...

Partial penile disassembly?! That's the wackiest label I've heard. Vitamin E is also worthless advice, it appears to be not only useless but it may have harmful systemic effects in high doses. On the other hand, the rest of the advice is pretty accurate and nicely put.

The notable thing about this post, though, is not the description of Peyronie's. It's that the disease has been publicly "outed". Thanks Peter!

Predicting the progression of Peyronie's: An utrasound study

2007-08-19T11:38:00.000-07:00

It's a mark of how under-studied Peyronie's has been that we're only now beginning to understand the course of the disorder (see also). These Greek researchers divided their study group up based on initial ultrasound, then followed their course for a year without intervention (emphases mine):

The Natural History of Peyronie's Disease: An Ultr...[Eur Urol. 2007] - PubMed Result

Eur Urol. 2007 Jul 17
The Natural History of Peyronie's Disease: An Ultrasonography-Based Study.
Bekos A, Arvaniti M, Hatzimouratidis K, Moysidis K, Tzortzis V, Hatzichristou D.
Center for Sexual and Reproductive Health and 2nd Department of Urology, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Greece.

OBJECTIVES: To define ultrasonographic patterns reflecting different states of Peyronie's disease (PD) and to use them to evaluate the natural history of the disease.

MATERIAL AND METHODS: Diagnosis of PD was based on medical and sexual history, physical examination, intracavernosal injection test, and penile ultrasonography. Patients with penile fracture history were excluded from the study. Three groups were formed according to ultrasonographic patterns: solitary hyperechoic lesion without acoustic shadow (group A), moderately hyperechoic multiple scattered calcified lesions with acoustic shadows (group B), dense calcified hyperechoic plaque with acoustic shadow (group C). All patients entered a watchful waiting protocol for 1 yr followed by a new penile ultrasonography.

RESULTS: Ninety-five 95 patients with PD were included in the study (mean age, 57.2+/-9.1 yr; mean duration of disease, 12.9+/-8.9 mo). Risk factors associated with cardiovascular disease were present in 79 of 95 patients (83.16%). Eleven (11.6%), 35 (36.8%), and 49 (51.6%) patients were classified into groups A, B and C, respectively.

At the end of the study, in group A, reduction of fibrotic lesions and curvature angle was noticed in 9 of 11 (81.8%) patients, whereas plaque formation was noticed in 2 of 11 (18.2%) patients. In group B, plaque and curvature reduction was noticed in 15 of 35 (42.9%) and 12 of 35 (34.3%) respectively, whereas in the rest a dense calcified plaque was noticed. In group C, no ultrasonographic evidence of improvement was noticed; curvature angle was reduced in 4 of 49 (8.2%), owing to the extension of the plaque circumferentially. Significant hemodynamic changes were noticed at the two time points tested (30.53% diagnosed with vascular disease at baseline vs. 46.32% at the end of the study, p=0.03).

CONCLUSIONS: Corporal ultrasonography in patients with PD allows objective evaluation and classification of disease. The density of echogenic areas and presence of acoustic shadows are predictors of disease stability.

PMID: 17673362 [PubMed - as supplied by publisher]

If this holds up urologists will be better decide when aggressive treatment is indicated. The overall news was not encouraging and is line with other recent studies of disease course. This was an older population and thus might be expected to have less aggressive disease, but in fact only 11% fell into the "good" group at the start of the study. Half were in the "bad" group at the start and none of them improved.

Peyronie's Proteomics

2007-08-19T11:27:00.000-07:00

A few weeks ago I wrote:

Peyronie's Disease - the blog: Proteomics in Peyronie's Disease - including a review of gene profiling in PD: "As I wrote a couple of days ago, even an area as understudied as Peyronie's can advance quickly when new instruments are brought to bear on old questions. Proteomics is all the rage in our post-genomic era, but besides the faddish topic the article claims to have reviewed the full literature on gene profiling in PD (of course that probably took about 3 hours)."

Coincidentally, I've since had to do a review of protein network research and disease definition.

I now understand that one of the promises of protein networks is the ability to redefine diseases, which includes grouping differing syndromes into single disease classes and dividing a disease into subtypes -- or eliminating the disease/syndrome altogether. Protein networks, in other words, may do for our understanding of disease in humans what DNA research has done for defining and redefining species.

So this research may, for example, tell us if there really are important relationship between Peyronie's, Duputren's and other disorders of fibrosis.

Clostridial Collagenase treatment for Peyronie's, Dupytren's and Frozen Shoulder syndrome

2007-08-19T11:22:00.000-07:00

I usually don't pay attention to press releases on clinical trials -- they're fishing expeditions for investors and/or speculators. This one caught my eye because of the focus on several diseases of pathologic fibrosis:

Auxilium Pharmaceuticals, Inc. Receives Clearance to Resume Clinical Trials for XIAFLEX(TM)

Auxilium Pharmaceuticals, Inc. (Nasdaq: AUXL) today announced that the Company has received clearance from the U.S. Food and Drug Administration ('FDA') to resume its phase III clinical trials for XIAFLEX (clostridial collagenase for injection), formerly referred to as AA4500, in the treatment of Dupuytren's contracture.
... The Company plans to initiate a pivotal double-blind trial in the U.S., a double-blind trial in Australia, and two open label trials that along with previously conducted trials will serve as the basis for the Biologics License Application ('BLA') for marketing approval from the FDA....

... Auxilium has four projects in clinical development. XIAFLEX(TM) (clostridial collagenase for injection), formerly referred to as AA4500, is in phase III development for the treatment of Dupuytren's contracture and is in phase II development for the treatment of Peyronie's disease and Frozen Shoulder syndrome (Adhesive Capsulitis).

Dupuytren's disease: does it really affect 25% of northern Europeans?

2007-08-04T19:34:00.001-07:00

We know Peyronie's Disease is more common than once though among white males over age 50, and there's long been thought to be an association with Dupuytren's contracture. So I've been learning a bit about Dupuytren's. I was very surprised to see a news article claiming that 25% of western European men will develop Dupuytren's Disease. That seemed absurdly high. I finally got around to researching that number (italics mine)

Epidemiology of Dupuytren's disease: clinical, ser...[J Clin Epidemiol. 2000] - PubMed Result

1: J Clin Epidemiol. 2000 Mar 1;53(3):291-6. Epidemiology of Dupuytren's disease: clinical, serological, and social assessment. The Reykjavik Study. Gudmundsson KG, Arngrímsson R, Sigfússon N, Björnsson A, Jónsson T. The Health Care Centre, 540, Blonduos, Iceland. kristgud@isholf.is

Dupuytren's disease or palmar fibromatosis is a common disabling hand disorder, mainly confined to Caucasians of northwestern European origin. The prevalence of Dupuytren's disease and possible risk factors related to the disease were evaluated in a random sample of 1297 males and 868 females, aged 46 to 74 years. Blood samples were collected and biochemical parameters were evaluated. The possible relation between the disease and clinical, social, and biochemical parameters were estimated with age-adjusted univariate logistic regression analysis. Altogether 19.2% of the males and 4.4% of the female participants had clinical signs of Dupuytren's disease. The prevalence increased with age, from 7.2% among males in the age group 45-49 years up to 39.5% in those 70-74 years old. The more severe form of the disease, finger contractures, was found in 5.0% of the men and 1.4% had required operation, while this was rarely seen among women. In men elevated fasting blood glucose (P < 0.04), low body weight, and body mass index were significantly correlated with the presence of the disease (P < 0.001). Dupuytren's disease was common among heavy smokers (P = 0.02) and those having manual labor as occupation (P = 0.018). These results show that Dupuytren's disease is common in the Icelandic population and occupation and lifestyle seem to be related to the disease.

So the answer is that 25% is perhaps true for north-western Caucasian Europeans, but it refers to early signs of the disease. The prevalence of contractures in this population is only 5%, and Scandinavians appear to have the highest risk of all. On the other hand I was unable to find any literature suggesting Scandinavians were particularly prone to Peyronie's disease. The number is misleading in the context of the news article.

Treating Dupuytren's disease

2007-07-24T21:24:00.000-07:00

There's some correlation between Peyronie's disease and Dupuytren's contracture, though the structures involved are fairly different. So this treatment for Dupuytren's, a disorder for which there's been no good treatment, is at least of passing interest:

Straightening Bent Fingers, No Surgery Required - New York Times

Keith Felcyn, a retired senior editor of BusinessWeek magazine who lives in Greenwich, Conn., had not been able to fully extend the little and ring fingers of his left hand for 20 years. But last month, it took 20 minutes for a doctor in Ontario, Ore., to reverse his Dupuytren’s disease, a benign but ultimately disabling disorder in which the fascia of the hand thickens and draws the fingers permanently into the palm.

The disabling disorder causes patients’ fingers to become fixed in a bent position.

“When he finished and I could lay my hand flat,” Mr. Felcyn recalled, “I said, ‘My God, this is a miracle.’ ”

The procedure, called needle aponeurotomy or percutaneous fasciotomy, involves using the bevel of a hypodermic needle to essentially shred the ropes of constricting fascia characteristic of Dupuytren’s disease. The disorder, named for Baron Guillaume Dupuytren, a 19th-century French surgeon who wrote about it, afflicts up to 25 percent of people over 40 in Western countries and is most common in men of northern European descent. Ronald Reagan had it; so does Margaret Thatcher. Risk factors for the disease include hand or wrist trauma, repetitive strain, alcoholism, smoking and diabetes.

Needle aponeurotomy, which leaves only superficial puncture wounds, was developed 30 years ago by a group of French rheumatologists and is now being practiced in the United States by fewer than a dozen physicians. Thousands of patients like Mr. Felcyn are flocking to these doctors every year, many against the advice of hand surgeons who say open hand surgery is more effective.

“Surgery has a lower recurrence rate,” said Dr. Richard Gelberman, chairman of the department of orthopedics at Washington University in St. Louis, and president of the American Society for Surgery of the Hand. The recurrence rate for needle aponeurotomy is around 50 percent after three years, according to several studies published in French medical journals. Studies in the British and American medical literature indicate that the recurrence rate for fasciectomy, or surgical removal of the diseased fascia, is 40 percent after five years.

But surgery carries a significantly higher risk of complications like nerve and vascular injury, infection, inflammation and something called a flare reaction in which the hand gets very swollen, red and stiff.

“Fasciectomy is a delicate procedure that requires meticulous technique,” said Dr. Steven Z. Glickel, director of the C.V. Starr Hand Surgery Center at St. Luke’s-Roosevelt Hospital Center in New York. Moreover, he added, “Patients have to be committed to physical therapy” for six weeks to four months before they can expect to regain full function of the hand.

Mr. Felcyn played tennis the day after his needle aponeurotomy, which, unlike surgery, can be easily repeated should he have a recurrence.

Dr. David Kline, who performed the procedure using a mild local anesthetic, had the same thing done to both his hands five years earlier in France.

“I cried the day I had it done,” Dr. Kline said. “I was so happy to be able to use my hands.” As an emergency room doctor, he had thought his career was over until an Internet search turned up a group of rheumatologists at the Hôpital Lariboisière in Paris offering an alternative to surgery.

Dr. Kline paid 40 euros, about $55, to undergo the procedure. He returned to Paris in 2005 to receive training in the technique. Dr. Kline said he had since performed more than 600 needle aponeurotomies, in addition to continuing to practice emergency medicine, at Holy Rosary Medical Center, in Ontario, Ore.

There is little competition because so few doctors offer it in the United States; a list can be found at http://www.dupuytren-online.info/needle-aponeurotomy.html.

The cost is $500 to $650 per affected finger and is covered by Medicare.

Dr. Charles Eaton, a hand surgeon in Jupiter, Fla., said the technique had been slow to gain acceptance by other American surgeons because “it sounds crazy to work on the delicate structures of the hand without cutting it open to see what you are doing,” especially when Dupuytren’s disease often distorts the anatomy of the hand.

But because patients are awake for the procedure, he said they can report a tingling sensation if the one-half millimeter needle gets too close to a nerve, and they can move their fingers to reveal the location of tendons.

“It took a long time for arthroscopy to take hold, too,” Dr. Eaton said.

It would be interesting to understand exactly how and why this works. I was surprised by the cited prevalence for Dupuytren's. If it's really that common (25%?! of all men over 40?) then any historic association with Peyronie's may be completely coincidental.

Update 8/4/07: The prevalence of contractures is not 25%. Amongst Caucasian European males over age 40 it's probably 1-4%, and maybe 5%+ in Scandinavians.

Proteomics in Peyronie's Disease - including a review of gene profiling in PD

2007-07-06T19:49:00.000-07:00

This article isn't published yet, the abstract is from an electronic preprint:

Is There a Role for Proteomics in Peyronie's Disea...[J Sex Med. 2007] - PubMed Result

...This review assesses the potential use of protein alterations measured by various novel technologies, to predict progression, regression, or stabilization of PD in an affected individual. Methods. A comprehensive literature review of the past decade in the field of gene profiling and protein expression of PD was performed...

As I wrote a couple of days ago, even an area as understudied as Peyronie's can advance quickly when new instruments are brought to bear on old questions. Proteomics is all the rage in our post-genomic era, but besides the faddish topic the article claims to have reviewed the full literature on gene profiling in PD (of course that probably took about 3 hours).

This is one article I'm going to have to drag out of the university library -- once it's published!

Another 1960s article on Peyronie's and other "collagen" disorders

2007-07-06T19:30:00.000-07:00

This French article from 1964 is the second I've come across discussion combinations of Peyronie's disordr with other disorders of fibrosis ("collagen" in those days): [A COLLAGEN TRIAD: LA PEYRONIE'S DISEASE, DUPUYTRE...[J Urol Nephrol (Paris). 1964]

It's an area of research that died out in the 1960s apparently.

The triad was "PEYRONIE'S DISEASE, DUPUYTREN'S DISEASE AND FIBROSIS OF THE AURICULAR CARTILAGE". I don't know the last, but for what it's worth I used to have odd lumps of fibrous material in my pinnae (soft tissue at base of the auricle) though they've since faded.

It would be interesting to get hold of one of these old, old articles ....

Peyronie's Disease: Type I and Type II?

2007-07-06T19:15:00.000-07:00

I've been thinking about the results of a very recent study of the natural history of Peyronie's Disease. I'm thinking the study suggests that there may be two types of Peyronie's disease, early onset (Type I?) and late onset (Type II?) with an age cutoff of 50.

Fifty is a special age. Throughout most of human evolution men did not live past fifty. Nothing is really designed to last that long; life much past fifty requires a cozy environment and, often, some medical care. So things that go wrong after fifty are often normal "wear and tear". That's a clue.

My guess is that Peyronie's after 50 is mostly a bit of bad luck. The course of late onset Peyronie's is relatively benign. Progression is limited. Symptoms may resolve. It sounds more like an unlucky tear or injury to a sub-optimal tunica albuginea than a true disease. It's a vulnerable structure, sometimes it's less well made, it can tear.

Early onset Peyronie's, developing before age 50, is another story. The disease seems to progress, and may do so without evidence of repeated trauma. This seems more like a pathologic process, a genetic disorder of fibrocyte perhaps.

They may be the same condition of course, or related conditions, but I suspect we'll learn more about Peyronie's if we study early onset and late onset disease separately. If we study them together, we may miss important signals in the noise.

The shared items page - an article from 1965

2007-07-05T21:10:00.000-07:00

In a prior post I described how to create feeds to track publication activity in the National Library of Medicine. Since I'm thinking Peyronie's is probably a systemic disorder of fibrocyte function one of my searches tracks articles that focus on both Dupuytren's contractures and Peyronie's disorder. You can see examples of some of those articles on my shared items page.

This is all about catching the latest news, so I was bemused when one of the articles I found was from 1965 ....

It's in German, so not that easy to follow up, but PubMed lets one track related articles, which included this one from 2004:

Qian A et al. Comparison of gene expression...[PMID: 15302515]

... CONCLUSIONS: These data demonstrate that the pattern of alterations in the expression of certain gene families in PD and DD is similar, suggesting that they share a common pathophysiology and may be amenable to the same therapeutic regimens.

Really, not a lot of progress in 40 years, but maybe things will start picking up ...

How to track research developments using syndication and an RSS reader

2007-07-05T20:22:00.000-07:00

One of the ways I track research developments is by using an advanced feature of the National Library of Medicine's PubMed database and Google Reader.*

For example, here is a PubMed RSS feed for "fibrocyte disorder" [1]. If you right click on the link to the left, copy and paste it into a feed reader, you'd see a feed.

Here's what I did:

Go to PubMed. (National Library of Medicine, once upon a time a similar product was called 'Grateful Med'. Those were the days.)
Enter your search string (ex. "fibrocyte disorder" and hit enter.
Now, look carefully atop the results for a drop down "button" called "Send To".
Click on "Send To" and choose "RSS Feed".
Now look for the XML icon and copy the link. Paste into Google Reader.

Here's another one, for example, for Peyronie's Disease. It's easy to create as many as you'd like, and the searches can be much more sophisticated than the simple examples above.

One feature of Google Reader is that you can select interesting articles and share those in turn. The page that one uses to share those can be viewed by a web browser, but it also has a feed. Here's the page, which I'll add to over time:

Incidentally, my standing search on Google News also provides RSS syndication, so I'm including that in my Google Groups Peyronie's collection and items I note of interest will be on the shared articles page too. (Actually, at the moment that service appears to be broken ...)
-----------------------
* A discussion of syndication clients is more than I want to get into. Bloglines and Google Reader are two web based clients, Firefox, IE 7 and Safari have reasonably good built-in readers, and their are several good dedicated readers for OS X and one good reader for XP (Onfolio).

[1] One of the ideas I'm exploring is that Peyronie's Disease is really a systemic fibrocyte disorder that manifests as penile deformation because of the unique vascular structure of the tunica albuginea. If so it should have a relationship to other disorders of fibrocyte function...

The course of Peyronie's disease

2007-07-04T21:27:00.000-07:00

This is just out: The natural history of Peyronie's disease. [Arch Esp Urol. 2007] - PubMed Result. I'll post later on how I get alerts about this kind of thing, but here are the key results from the study of 110 patients over at least five years (based only on the abstract):

1. Patients over 50 tend to stabilize or get better.
2. Patients under 50 tend to get worse. Almost 70% progressed to surgery.

Studies of the natural history of a disorder are hard to fund and hard to do. We need more of them. I don't know how good this one really is, the trick is how representative the initial sample is and how many are lost to follow-up. In general the patients who do worse tend to follow-up, so results of these studies tend to the "grim" side.

Grim is the word for the under-50 group, I really didn't think 70% would end up with surgery. Given that a significant number may have decided to give up on intercourse, it really contradicts the general impression most urologists have about the course of the disorder.

Conversely older patients can do well, though again I wonder how many just decide to give up.

Needless to say, no medical therapy seems to make any difference. Bad numbers, no doubt.

Why research Peyronies? To understand asthma, heart disease, chronic cystitis ...

2007-07-04T20:38:00.000-07:00

If Peyronie's is best understood as a hyperactive fibrosis disorder, then it makes sense to look at other fibrotic disorders for clues to Peyronie's. This 2007 article provides a nice overview of current thinkings on disorders of the fibrotic response (emphases mine, I've always been fond of moncytes ..):

The role of the fibrocyte, a bone marrow-derived m...[Lab Invest. 2007] - PubMed Result
... Human fibrocytes are mesenchymal progenitors that exhibit ... characteristics of hematopoietic stem cells, monocytes and fibroblasts. They likely represent the obligate intermediate stage of differentiation into mature mesenchymal cells of a bone marrow-derived precursor of the monocyte lineage ...
... human fibrocytes produce large quantities of extracellular matrix components and further differentiate into cells identical to the contractile myofibroblasts that emerge at the tissue sites during repair processes and in some fibrotic lesions. ...
...a causal link between fibrocyte accumulation and ongoing tissue fibrogenesis or vascular remodeling in response to tissue damage or hypoxia. Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in human hypertrophic scars, in the skin of patients affected by nephrogenic systemic fibrosis, in human atherosclerotic lesions, and in pulmonary diseases characterized by repeated cycles of inflammation and repair, like asthma. The presence of fibrocyte-like cells has been reported in human chronic pancreatitis and chronic cystitis. Similar cells also populate the stroma surrounding human benign tumors...

Well, there you go. Perhaps understanding Peyronie's may provide valuable clues for understanding asthma, atherosclerosis (heart disease) and chronic pancreatitis. After all, the lesions of Peyronie's are much easier to biopsy than those of cardiac vessels or pulmonary alveoli. If that's not good for funding, I don't know what is.

I looked earlier for an association between keloid (hypertrophic) scars and Peyronie's, but I couldn't find any. That would be a good question for the Peyronie's Society forum though. For the record, I have both Peyronie's and a nasty keloid scar.

Chronic cystitis is the bane of urologists. One wonders if it could be the female equivalent to Peyronie's. Now I admit that's a bit nutty, but it wouldn't hurt to ask women with chronic cystitis if they have relatives with Dupuytren's contractures (they probably wouldn't know of male relatives with Peyronie's).

Update 7/4/07: After my wild speculation on Dupuytren's and chronic insterstitial cystitis I tried a Google search on the combo and got this tantalizing fragment from last year:

Dupuytren's contracture is associated with sprouting of substance ...
... 10 We propose that Dupuytren's contracture is an inflammatory disease dominated by mast cells, bearing similarities to interstitial cystitis. ...
ard.bmjjournals.com/cgi/content/full/65/3/414

I swear I didn't know that was out there. Alas, I can't get at the full text of the article, I'll have to try it from my U account another time. It's the only one and it sounds like an aside deep in the text, but maybe my speculation wasn't quite as whacky as I thought it was ...

Peyronie's Disease Society public forum

2007-07-04T19:52:00.000-07:00

Peyronie's is a relatively common, though generally concealed, disorder. It may affect as many as 1/100 men, though I suspect the "significant impact" number is closer to 1/300 or so.

For such a relatively common and rather significant (to us) disorder, there's not much on the net -- lots of brief introductions, very little discussion, quite a few scams.

There's one notable exception: the Peyronie's Disease Society - Forum, which is the communication center for the Peyronie's Disease Society. The PDS is so pure it doesn't even seem to have advertising:

... We are non-profit. We have no commercial interests, and are funded solely from the personal finances of our management team. Our membership base actively contributes to information, education, and support, through our Peyronies Disease Forum...

I've browsed the forums, and, given my background, it's not surprising that I'm familiar with most of the science and discussion topics. There's a lot of enthusiasm for topics I'm not interested in (various vitamins, DHEA, etc), but there's also discussion of surgical interventions and results. That kind of data is very hard to find.

I'll be browsing the forums on a semi-regular basis, looking for topics that suggest some literature research.

Clinton has Peyronie's Disease?!

2007-07-04T19:27:00.000-07:00

You know, and I say this more seriously than you might imagine, this may explain quite a bit.

This is from the BBC article on PD:

BBC - Health - Ask the doctor - Peyronie's disease:

...Although Peyronie's disease is quite common - it's thought to affect about one in 100 men - few have heard of it. At least they hadn't until a couple of years ago when, in the US, Paula Jones filed a sexual misconduct lawsuit against President Clinton. She swore intimate knowledge of the President by describing a distinguishing penile condition whereby there's a distinctly angled bend visible when the penis is erect...

Maybe I could get Bill to join this blog. I completely shut out all the Paula Jones news, apparently I ought to read the tabloids more closely.

Other than that fragment of some interest, there's not much else in the BBC essay, indeed it's quite dated.

Pathologic fibrosis: implications for treatment and research

2007-07-04T19:14:00.000-07:00

We suspect that Peyronie's is a genetic disorder, in some cases inherited, that is characterized by hyperactive fibrosis. Although Peyronie's is a disorder of the tunica albuginea of the male penis, it's likely that the hyperactive fibrosis manifests throughout the body (pathologic scarring?).

So what are the clinical implications of this knowledge?

urologists should be wary of urologic procedures in men who have relatives with Dupuytren's contracture (or Peyronie's, but they won't know of the latter).
research in other disorders characterized by pathologic hyper-fibrosis may have implications for understanding Peyronie's -- and vice-versa. (I'll be looking to see if there are any such disorders with significant funding. Hmmm. Maybe fibrosis in the intima of cardiac vessels?)
the best treatment for Peyronie's will probably be a locally applied medication that reduces fibrosis and is administered with very early symptoms in persons with a known predisposition (eg. family history) of the disorder

Peyronie's and chromosomal abnormalities

2007-07-04T18:56:00.000-07:00

In my prior post I reviewed the OMIM entry on Peyronie's. That entry cited a 1987 and a 1991 (yeah, research is slow in this domain) article on chromosomal anomalies in the abnormal plaque tissue of the tunica albuginea found in Peyronie's disease.

These articles make the plaques seem more like a tumor than a conventional scar. Pubmed lets one query for "related articles" on a given topic, here's what that query looks like:

Multiple clonal chromosome abnormalities in Peyronie's disease - 1991

One of the articles that turned up was interesting, emphases mine:

Mulhall JP et al. Chromosomal instability is de...[PMID: 14961053]

... Peyronie's disease is a fibrotic disorder, a condition characterized by cellular proliferation and excess extracellular matrix production. Previous work in related conditions has demonstrated chromosomal instability. This investigation was undertaken to analyze fibroblasts derived from Peyronie's disease tunical tissue for abnormalities of chromosome number and progression of cytogenetic aberrations during cell culture...

... Peyronie's disease plaque-derived fibroblasts demonstrated frequent aneusomies in chromosomes 7, 8, 17, 18 and X and recurrent deletions of chromosome Y. Peyronie's disease nonplaque tunica-derived fibroblasts demonstrated infrequent chromosomal changes early in culture; however, with repeated passaging the majority of cell cultures demonstrated aneusomies [ed: extra copies] in at least one chromosome. These data indicate that Peyronie's disease plaque-derived fibroblasts have consistent aneusomies even at early passage and that nonplaque tunica-derived cells from men with Peyronie's disease also demonstrate chromosomal instability. This suggests that the tunica albuginea of men with Peyronie's disease may be predisposed to undergoing unregulated fibrosis. These findings confirm the transformed nature of the Peyronie's disease tunical fibroblasts studied in this analysis. While the etiology of these findings is not clear, it is likely that these pathobiological characteristics contribute to the pathophysiology of this disease process.

In other words men who develop Peyronie's Disease have something wrong with all the cells of their "tunica albuginea", not only those involved in Peyronie's. Of course this implies there's something wrong with at least those cells everywhere in the body.

In particular the cells are prone to a crazed kind of fibrosis (tough fiber generation) instead of a reasoned, measured, sort of fibrotic reaction.

It would be interesting to know what other conditions this presumably genetic defect may predispose to -- besides Dupuytren's contracture.

From a science point of view, this study tells us something fairly interesting. There's very little active research in Peyronie's, but it's studied using tools that are developed for other, actively studied, domains. A competent researcher can simply repeat a study from 10 years ago, and by virtue of better tools new knowledge will emerge.

OMIM - The Peyronie Discussion

2007-07-04T18:31:00.000-07:00

OMIM, the "online mendelian inheritance in man" NIH database, published out of Johns Hopkins, is a formidable reference source. The discussion of "Peyronie Disease", however, is a bit eccentric. For example: "An anonymous nongeneticist suggested to me in 1980 that Peyronie disease is 'sex-linked with reduced penetrance.'" Cough. That doesn't show up in most of the OMIM posts, I get a feeling this one is under-edited.

Even so, I've excerpted and bolded some sections.

OMIM - PEYRONIE DISEASE
... Bias et al. (1982) concluded that this phenotype is a male-limited, autosomal dominant trait. They traced Peyronie disease through several families. Dupuytren contracture was often present in both males and females. In 1 kindred, males in 3 successive generations had Peyronie disease and Dupuytren contractures, and the latter was present in a fourth generation. Close linkage with HLA (see 142800) was excluded. Chromosomal abnormalities were described by Somers et al. (1987) and by Guerneri et al. (1991).

In Rome, Carrieri et al. (1998) performed a case-control study of 134 men with Peyronie disease and 134 male controls. Men who had undergone invasive procedures on the penis (e.g., urethral catheterization, cystoscopy, and transurethral prostatectomy) had a 16-fold increased risk of Peyronie disease, while a nearly 3-fold increase was observed among men who had genital and/or perineal trauma. ...
... Dupuytren contracture was found in 21% of cases and none of the controls, and 4% of the cases and none of the controls reported familial history for Peyronie disease.

Note that the key research on the genetics of Peyronie's was done twenty-five years ago, and yet it's omitted from most discussions of the disorder (I'll be adding it to Wikipedia.) I was very surprised by the 16-fold increase with urethral catheterization.

If I were a urologist, I would routinely ask prior to any urologic procedure whether the patient had any relatives with Dupuytren's contracture. If they did, I'd reconsider the need for the procedure. A 16-fold increase is enormous.

It's most likely that Peyronie's Disease is a pathologic reaction to common micro-trauma of the penile vasculature. Men who don't carry* the gene may develop small scars or non-significant plaques, men who carry the gene* develop plaques and pathologic scarring.

* Genetics is far more complex than it once was. Now when we say "carry" we mean something like "a complex of interacting genetic material" with one or more interacting mutations.

Peyronie's disease - the Wikipedia article

2007-07-04T18:16:00.000-07:00

The primary purpose of the blog is provide material I'll use to make the Peyronie's disease - Wikipedia article as robust as possible.

As of 7/04 it's a very brief article, but it's pretty high quality. I'll be gradually expanding and adding to it.

What is it like to have this disease?

2007-07-04T18:11:00.000-07:00

How bad is it to have Peyronie's?

Well, it won't kill you, it's not contagious (though a predispositon to the disease is inherited) and it won't prevent most kinds of employment. On the other hand, if you get severe Peyronie's before age forty you have a right to feel that life has seriously dumped on you. If you get it after age 70 (unlikely) you probably can't complain quite as much.

I think for most of us the impact is similar to losing an eye (one, not two), a hand, or developing a treatable malignancy. It's a big personal impact and it takes a significant amount of time to work through.

Why the URL?

2007-07-04T18:04:00.000-07:00

The url for this blog is "thebentnail.blogspot.com". This old colloquial name for "penile induration" (Peyronie's Disease) wasn't my first choice, but "peyronies.blogspot.com" and "peyroniesdisease.blogspot.com" were taken by "blogspot squatters".

So we go with the funny one.

About this blog

2007-07-04T17:51:00.000-07:00

I have Peyronie's Disease, also known as "penile induration" and sometimes informally called "bent nail syndrome". I've had it for about thirteen years, but an exacerbation a year ago took it from moderate to severe and effectively "disabling".

This is not a common disease, but it's not as rare as you might think. It's not something men tend to talk about. I suspect the disease runs in my family since several male relatives have "Dupuytren's contracture", a related disorder -- but nobody talks about their broken organs. I think that's understandable. There's a reason this blog is published under a pseudonym.

There's not much research into Peyronie's disease, and our knowledge of the disorder has progressed very little since the 1980s. There are no effective medical therapies, few clinical trials, no drug research, and the surgical treatments are nothing to brag about. There is lots of misinformation and a bit of exploitation.

Although I'm a physician, I won't be dedicating my life to researching the disorder. I've got other commitments I have to follow. I would like, however, to spin something positive out of my affliction. I intent to contribute to the wikipedia page on Peyronie's, and to use this blog to help build that material. I will also market it a bit for those who might be interested in my own personal perspective.

This blog is my personal perspective. I'm sympathetic to the desperation that drives people to "alternative therapies" (Vitamin E, alas, is now in that category), but I'm a science guy. So, no alternative therapies, none of the various scams, nada. No ads either.