Peyronie's emerges from the closet

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

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

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

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?

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

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

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!