Pudendal Nerve Implant May Help Reduce Pelvic Pain

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LAKE BUENA VISTA, FLA. — Pudendal nerve neuromodulation may hold promise for some patients with refractory chronic pelvic pain syndrome, according to the findings of a small study.

Multiple treatment approaches have been tried for refractory chronic pelvic-perineal pain (RCPPP), but results have been suboptimal and temporary. Because sacral neuromodulation has been used with some success in refractory painful bladder syndrome/interstitial cystitis, pudendal neuromodulation has been proposed as a possible treatment for RCPPP. The procedure also has been suggested for patients with interstitial cystitis who failed sacral neuromodulation, according to Dr. Maude Carmel of the urology department at Sherbrooke (Que.) University Hospital Centre.

Ten of Dr. Carmel's patients have undergone treatment with pudendal neuromodulation (seven patients with RCPPP and three with interstitial cystitis). The patients' mean age was 53 years, and the mean duration of symptoms was 14 years. Seven patients were women; prior treatments included perineal physiotherapy, nerve and caudal blocks, and sacral neuromodulation.

“After a trial period of 3–6 weeks, one patient with interstitial cystitis and two with RCPPP reported more than 60% improvement in their symptoms and elected to have a permanent generator implanted,” Dr. Carmel wrote in a poster session at the annual meeting of the International Pelvic Pain Society.

All three continued to experience improvements of more than 80% after 1 year. The remaining seven were considered treatment failures. No major complications occurred. There have been no infections and no complications after electrode removal.

The procedure involves implantation of a tined quadripolar electrode under electrophysiologic and radiologic guidance. Needle electrodes are placed at the external anal sphincter, the gluteus medius and maximus, the adductor longus, the tibialis, and the gastrocnemius muscles.

Implantation is done under fluoroscopy, using a dorsal percutaneous approach at the level of the ischial spine. The quadripolar electrode is then tunneled under the skin and connected to the external neurostimulator.

One possible etiology for RCPPP is pudendal nerve (PN) neuralgia, which is characterized by pain in the genitalia, perineum, and anorectal region. The pain is aggravated by sitting or by flexion of the hip, and is relieved by standing, lying down, or sitting on a lavatory seat or commode.

The PN arises from the S2-S4 roots of the sacral plexus, exiting the pelvis under the piriformis muscle through the greater sciatic foramen and descending ventral to the sacrotuberous ligament. It provides sensory innervation to the anal, perineal, and genital areas and motor supply to the pelvic floor muscles.

Entrapment or compression of this nerve can cause pelvic floor overactivity and perineal trauma and inflammation, according to Dr. Carmel.

No conflicts of interest were reported in Dr. Carmel's poster presentation.

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LAKE BUENA VISTA, FLA. — Pudendal nerve neuromodulation may hold promise for some patients with refractory chronic pelvic pain syndrome, according to the findings of a small study.

Multiple treatment approaches have been tried for refractory chronic pelvic-perineal pain (RCPPP), but results have been suboptimal and temporary. Because sacral neuromodulation has been used with some success in refractory painful bladder syndrome/interstitial cystitis, pudendal neuromodulation has been proposed as a possible treatment for RCPPP. The procedure also has been suggested for patients with interstitial cystitis who failed sacral neuromodulation, according to Dr. Maude Carmel of the urology department at Sherbrooke (Que.) University Hospital Centre.

Ten of Dr. Carmel's patients have undergone treatment with pudendal neuromodulation (seven patients with RCPPP and three with interstitial cystitis). The patients' mean age was 53 years, and the mean duration of symptoms was 14 years. Seven patients were women; prior treatments included perineal physiotherapy, nerve and caudal blocks, and sacral neuromodulation.

“After a trial period of 3–6 weeks, one patient with interstitial cystitis and two with RCPPP reported more than 60% improvement in their symptoms and elected to have a permanent generator implanted,” Dr. Carmel wrote in a poster session at the annual meeting of the International Pelvic Pain Society.

All three continued to experience improvements of more than 80% after 1 year. The remaining seven were considered treatment failures. No major complications occurred. There have been no infections and no complications after electrode removal.

The procedure involves implantation of a tined quadripolar electrode under electrophysiologic and radiologic guidance. Needle electrodes are placed at the external anal sphincter, the gluteus medius and maximus, the adductor longus, the tibialis, and the gastrocnemius muscles.

Implantation is done under fluoroscopy, using a dorsal percutaneous approach at the level of the ischial spine. The quadripolar electrode is then tunneled under the skin and connected to the external neurostimulator.

One possible etiology for RCPPP is pudendal nerve (PN) neuralgia, which is characterized by pain in the genitalia, perineum, and anorectal region. The pain is aggravated by sitting or by flexion of the hip, and is relieved by standing, lying down, or sitting on a lavatory seat or commode.

The PN arises from the S2-S4 roots of the sacral plexus, exiting the pelvis under the piriformis muscle through the greater sciatic foramen and descending ventral to the sacrotuberous ligament. It provides sensory innervation to the anal, perineal, and genital areas and motor supply to the pelvic floor muscles.

Entrapment or compression of this nerve can cause pelvic floor overactivity and perineal trauma and inflammation, according to Dr. Carmel.

No conflicts of interest were reported in Dr. Carmel's poster presentation.

LAKE BUENA VISTA, FLA. — Pudendal nerve neuromodulation may hold promise for some patients with refractory chronic pelvic pain syndrome, according to the findings of a small study.

Multiple treatment approaches have been tried for refractory chronic pelvic-perineal pain (RCPPP), but results have been suboptimal and temporary. Because sacral neuromodulation has been used with some success in refractory painful bladder syndrome/interstitial cystitis, pudendal neuromodulation has been proposed as a possible treatment for RCPPP. The procedure also has been suggested for patients with interstitial cystitis who failed sacral neuromodulation, according to Dr. Maude Carmel of the urology department at Sherbrooke (Que.) University Hospital Centre.

Ten of Dr. Carmel's patients have undergone treatment with pudendal neuromodulation (seven patients with RCPPP and three with interstitial cystitis). The patients' mean age was 53 years, and the mean duration of symptoms was 14 years. Seven patients were women; prior treatments included perineal physiotherapy, nerve and caudal blocks, and sacral neuromodulation.

“After a trial period of 3–6 weeks, one patient with interstitial cystitis and two with RCPPP reported more than 60% improvement in their symptoms and elected to have a permanent generator implanted,” Dr. Carmel wrote in a poster session at the annual meeting of the International Pelvic Pain Society.

All three continued to experience improvements of more than 80% after 1 year. The remaining seven were considered treatment failures. No major complications occurred. There have been no infections and no complications after electrode removal.

The procedure involves implantation of a tined quadripolar electrode under electrophysiologic and radiologic guidance. Needle electrodes are placed at the external anal sphincter, the gluteus medius and maximus, the adductor longus, the tibialis, and the gastrocnemius muscles.

Implantation is done under fluoroscopy, using a dorsal percutaneous approach at the level of the ischial spine. The quadripolar electrode is then tunneled under the skin and connected to the external neurostimulator.

One possible etiology for RCPPP is pudendal nerve (PN) neuralgia, which is characterized by pain in the genitalia, perineum, and anorectal region. The pain is aggravated by sitting or by flexion of the hip, and is relieved by standing, lying down, or sitting on a lavatory seat or commode.

The PN arises from the S2-S4 roots of the sacral plexus, exiting the pelvis under the piriformis muscle through the greater sciatic foramen and descending ventral to the sacrotuberous ligament. It provides sensory innervation to the anal, perineal, and genital areas and motor supply to the pelvic floor muscles.

Entrapment or compression of this nerve can cause pelvic floor overactivity and perineal trauma and inflammation, according to Dr. Carmel.

No conflicts of interest were reported in Dr. Carmel's poster presentation.

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Is Exposure to Helminths Needed for Immunity?

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Is Exposure to Helminths Needed for Immunity?

The epidemic of immune diseases that swept through the developed world during the 20th century may have resulted from a disruption in the delicate balance achieved throughout evolution between humans and certain parasitic fellow travelers, according to Dr. Joel V. Weinstock.

Diseases such as inflammatory bowel disease (IBD) were rare before the 1920s, when public health efforts began making significant strides in cleaning up the water supply, modernizing sewage treatment, and improving farming practices. While these efforts clearly had major benefits in curtailing or eliminating exposure to many disease-causing pathogens, they also had the unintended consequence of removing exposure to beneficial or even necessary organisms.

“People today live very differently than they did throughout history. People used to live close to the soil, without indoor plumbing, often with direct exposure to animals,” said Dr. Weinstock, professor of medicine, Tufts Medical Center and Tufts University Sackler School of Graduate Biomedical Sciences, Boston.

The result was near universal colonization with helminths, which are complex wormlike animals that inhabit the gastrointestinal tract of mammals. Like the myriad bacteria also found in the gut performing important tasks such as producing vitamins and aiding in digestion, some helminths can cause disease in the host but many are relatively harmless and, in fact, are important regulators of our immune systems.

“We have known for many years that helminths exert a powerful effect on immunity in the host, primarily by inducing the regulatory arm of the immune system, which is important in reigning in the effector 'fight and kill' arm of the immune system,” he said. The regulatory arm hones and shapes the immune response to bacteria, viruses, and parasites, quelling the effects of the effector arm so as to prevent needless tissue damage.

At least one rheumatologist was skeptical. “This is an interesting theory—but just that. We need more documentation,” said Dr. Roy D. Altman, professor of medicine, rheumatology, and immunology at the University of California, Los Angeles, in an interview.

“In addition, longevity increases with the elimination of parasites. It may be that people are living longer and this allows them to get immune diseases like rheumatoid arthritis.”

When other researchers were investigating possible environmental causes for the increase in these diseases, such as exposure to food dyes or from vaccinations, Dr. Weinstock took a different approach, looking for something in the environment that had been protective and had been lost. “It occurred to us that the deworming of the population—a major public health project early in the 20th century—took place at the same time as the incidence of immunologic diseases really took off,” he said.

Moreover, diseases such as asthma, IBD, rheumatoid arthritis, and multiple sclerosis remain uncommon in less-developed parts of the world where helminthic colonization is still widespread.

Because Dr. Weinstock is a gastroenterologist with a special interest in immunology, his subsequent investigations in animals and humans have focused on IBD.

Initial animal experiments determined that helminth exposure could both prevent and reverse induced colitis in mice by inhibiting inflammatory cytokines such as tumor necrosis factor-β and interleukin (IL)-12 or by promoting the production of regulatory cytokines such as IL-10 and transforming growth factor-β (Int. J. Parasitol. 2007;37:457–64).

In a pilot study of 29 adult patients with longstanding, refractory Crohn's disease, patients were given a drink containing 2,500 specially prepared ova of Trichuris suis, the pig whipworm, every 3 weeks for 24 weeks. Ingestion of this helminth, which is similar to the human whipworm, causes a short-term colonization in the human gastrointestinal tract.

By the 12th week, 22 patients (76%) had responded to the treatment, with a decrease in the Crohn's disease activity index (CDAI) of more than 100 points or below 150, and 19 patients (66%) were in remission, with a CDAI below 150.

At the 24th week, 23 patients (79%) were responders and 21 (72%) were in remission (Gut 2005;54:87–90).

In a subsequent double-blind trial that enrolled 54 adult patients with ulcerative colitis, participants received 2,500 T. suis ova in a liquid drink or a placebo drink every 2 weeks for 12 weeks.

Favorable responses, with decreases in the ulcerative colitis disease activity index of 4 or more points on an index ranging from 0 to 12, were seen in 13 patients receiving the active treatment (43%) compared with 4 receiving placebo (17%).

Similar findings have been shown in several other autoimmune conditions. Prospective data have shown that children with helminths are less likely to develop allergies, and disease has been arrested in patients with multiple sclerosis following helminth colonization. Researchers in the United Kingdom have been investigating modulation of the immune system in rheumatoid arthritis. They tested an anti-inflammatory phosphorylcholine-containing glycoprotein secreted by the nematode Acanthocheilonema viteae in collagen-induced arthritic mice, finding a reduction in the severity of arthritis and suppression of collagen-specific T-1 cytokine production (Ann. Rheum. Dis. 2008;67:518–23).

 

 

Dr. Weinstock believes that helminths and human hosts evolved to the benefit of both over millennia. Petrified human stool many thousands of years old has been found to contain helminth eggs, and autopsies of mummies have found traces of helminths. The frozen iceman Ötzi, found in the northern Italian Alps in 1991 where he had lain buried in a glacier since 3300 B.C., had T. trichiura in his gut.

“We are teeming with life, and we really are part of the environment. When we try to separate ourselves from the environment and exposures to these organisms, we leave ourselves predisposed to disease,” he said.

Dr. Weinstock is not advocating a return to 19th-century hygiene. Rather, he and others are working to characterize more fully the interaction of helminths with the immune system and to identify factors responsible for the beneficial exposures so they can be reintroduced at an appropriate time early in life, when the immune system is developing.

Clinical studies in IBD, asthma, rhinoconjunctivitis, and multiple sclerosis are underway and more are planned, and one helminth-derived medication, ASP1002, is under review by the Food and Drug Administration and the European drug monitoring authorities.

Dr. Francois-Xavier Frapaise, CEO of Asphelia Pharmaceuticals Inc., confirmed that his company is about to file an Investigational New Drug application for ASP1002 in Crohn's disease. They also are planning trials in various other conditions including lupus and multiple sclerosis. “RA would also be interesting to investigate,” he said.

“There has been a revolution in our thinking,” Dr. Weinstock said. “We have learned that we are not insulated from the world around us.”

Helminths, like this whipworm, could be the next big thing in multiple sclerosis and other autoimmune diseases. Courtesy Dr. Joel V. Weinstock

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The epidemic of immune diseases that swept through the developed world during the 20th century may have resulted from a disruption in the delicate balance achieved throughout evolution between humans and certain parasitic fellow travelers, according to Dr. Joel V. Weinstock.

Diseases such as inflammatory bowel disease (IBD) were rare before the 1920s, when public health efforts began making significant strides in cleaning up the water supply, modernizing sewage treatment, and improving farming practices. While these efforts clearly had major benefits in curtailing or eliminating exposure to many disease-causing pathogens, they also had the unintended consequence of removing exposure to beneficial or even necessary organisms.

“People today live very differently than they did throughout history. People used to live close to the soil, without indoor plumbing, often with direct exposure to animals,” said Dr. Weinstock, professor of medicine, Tufts Medical Center and Tufts University Sackler School of Graduate Biomedical Sciences, Boston.

The result was near universal colonization with helminths, which are complex wormlike animals that inhabit the gastrointestinal tract of mammals. Like the myriad bacteria also found in the gut performing important tasks such as producing vitamins and aiding in digestion, some helminths can cause disease in the host but many are relatively harmless and, in fact, are important regulators of our immune systems.

“We have known for many years that helminths exert a powerful effect on immunity in the host, primarily by inducing the regulatory arm of the immune system, which is important in reigning in the effector 'fight and kill' arm of the immune system,” he said. The regulatory arm hones and shapes the immune response to bacteria, viruses, and parasites, quelling the effects of the effector arm so as to prevent needless tissue damage.

At least one rheumatologist was skeptical. “This is an interesting theory—but just that. We need more documentation,” said Dr. Roy D. Altman, professor of medicine, rheumatology, and immunology at the University of California, Los Angeles, in an interview.

“In addition, longevity increases with the elimination of parasites. It may be that people are living longer and this allows them to get immune diseases like rheumatoid arthritis.”

When other researchers were investigating possible environmental causes for the increase in these diseases, such as exposure to food dyes or from vaccinations, Dr. Weinstock took a different approach, looking for something in the environment that had been protective and had been lost. “It occurred to us that the deworming of the population—a major public health project early in the 20th century—took place at the same time as the incidence of immunologic diseases really took off,” he said.

Moreover, diseases such as asthma, IBD, rheumatoid arthritis, and multiple sclerosis remain uncommon in less-developed parts of the world where helminthic colonization is still widespread.

Because Dr. Weinstock is a gastroenterologist with a special interest in immunology, his subsequent investigations in animals and humans have focused on IBD.

Initial animal experiments determined that helminth exposure could both prevent and reverse induced colitis in mice by inhibiting inflammatory cytokines such as tumor necrosis factor-β and interleukin (IL)-12 or by promoting the production of regulatory cytokines such as IL-10 and transforming growth factor-β (Int. J. Parasitol. 2007;37:457–64).

In a pilot study of 29 adult patients with longstanding, refractory Crohn's disease, patients were given a drink containing 2,500 specially prepared ova of Trichuris suis, the pig whipworm, every 3 weeks for 24 weeks. Ingestion of this helminth, which is similar to the human whipworm, causes a short-term colonization in the human gastrointestinal tract.

By the 12th week, 22 patients (76%) had responded to the treatment, with a decrease in the Crohn's disease activity index (CDAI) of more than 100 points or below 150, and 19 patients (66%) were in remission, with a CDAI below 150.

At the 24th week, 23 patients (79%) were responders and 21 (72%) were in remission (Gut 2005;54:87–90).

In a subsequent double-blind trial that enrolled 54 adult patients with ulcerative colitis, participants received 2,500 T. suis ova in a liquid drink or a placebo drink every 2 weeks for 12 weeks.

Favorable responses, with decreases in the ulcerative colitis disease activity index of 4 or more points on an index ranging from 0 to 12, were seen in 13 patients receiving the active treatment (43%) compared with 4 receiving placebo (17%).

Similar findings have been shown in several other autoimmune conditions. Prospective data have shown that children with helminths are less likely to develop allergies, and disease has been arrested in patients with multiple sclerosis following helminth colonization. Researchers in the United Kingdom have been investigating modulation of the immune system in rheumatoid arthritis. They tested an anti-inflammatory phosphorylcholine-containing glycoprotein secreted by the nematode Acanthocheilonema viteae in collagen-induced arthritic mice, finding a reduction in the severity of arthritis and suppression of collagen-specific T-1 cytokine production (Ann. Rheum. Dis. 2008;67:518–23).

 

 

Dr. Weinstock believes that helminths and human hosts evolved to the benefit of both over millennia. Petrified human stool many thousands of years old has been found to contain helminth eggs, and autopsies of mummies have found traces of helminths. The frozen iceman Ötzi, found in the northern Italian Alps in 1991 where he had lain buried in a glacier since 3300 B.C., had T. trichiura in his gut.

“We are teeming with life, and we really are part of the environment. When we try to separate ourselves from the environment and exposures to these organisms, we leave ourselves predisposed to disease,” he said.

Dr. Weinstock is not advocating a return to 19th-century hygiene. Rather, he and others are working to characterize more fully the interaction of helminths with the immune system and to identify factors responsible for the beneficial exposures so they can be reintroduced at an appropriate time early in life, when the immune system is developing.

Clinical studies in IBD, asthma, rhinoconjunctivitis, and multiple sclerosis are underway and more are planned, and one helminth-derived medication, ASP1002, is under review by the Food and Drug Administration and the European drug monitoring authorities.

Dr. Francois-Xavier Frapaise, CEO of Asphelia Pharmaceuticals Inc., confirmed that his company is about to file an Investigational New Drug application for ASP1002 in Crohn's disease. They also are planning trials in various other conditions including lupus and multiple sclerosis. “RA would also be interesting to investigate,” he said.

“There has been a revolution in our thinking,” Dr. Weinstock said. “We have learned that we are not insulated from the world around us.”

Helminths, like this whipworm, could be the next big thing in multiple sclerosis and other autoimmune diseases. Courtesy Dr. Joel V. Weinstock

The epidemic of immune diseases that swept through the developed world during the 20th century may have resulted from a disruption in the delicate balance achieved throughout evolution between humans and certain parasitic fellow travelers, according to Dr. Joel V. Weinstock.

Diseases such as inflammatory bowel disease (IBD) were rare before the 1920s, when public health efforts began making significant strides in cleaning up the water supply, modernizing sewage treatment, and improving farming practices. While these efforts clearly had major benefits in curtailing or eliminating exposure to many disease-causing pathogens, they also had the unintended consequence of removing exposure to beneficial or even necessary organisms.

“People today live very differently than they did throughout history. People used to live close to the soil, without indoor plumbing, often with direct exposure to animals,” said Dr. Weinstock, professor of medicine, Tufts Medical Center and Tufts University Sackler School of Graduate Biomedical Sciences, Boston.

The result was near universal colonization with helminths, which are complex wormlike animals that inhabit the gastrointestinal tract of mammals. Like the myriad bacteria also found in the gut performing important tasks such as producing vitamins and aiding in digestion, some helminths can cause disease in the host but many are relatively harmless and, in fact, are important regulators of our immune systems.

“We have known for many years that helminths exert a powerful effect on immunity in the host, primarily by inducing the regulatory arm of the immune system, which is important in reigning in the effector 'fight and kill' arm of the immune system,” he said. The regulatory arm hones and shapes the immune response to bacteria, viruses, and parasites, quelling the effects of the effector arm so as to prevent needless tissue damage.

At least one rheumatologist was skeptical. “This is an interesting theory—but just that. We need more documentation,” said Dr. Roy D. Altman, professor of medicine, rheumatology, and immunology at the University of California, Los Angeles, in an interview.

“In addition, longevity increases with the elimination of parasites. It may be that people are living longer and this allows them to get immune diseases like rheumatoid arthritis.”

When other researchers were investigating possible environmental causes for the increase in these diseases, such as exposure to food dyes or from vaccinations, Dr. Weinstock took a different approach, looking for something in the environment that had been protective and had been lost. “It occurred to us that the deworming of the population—a major public health project early in the 20th century—took place at the same time as the incidence of immunologic diseases really took off,” he said.

Moreover, diseases such as asthma, IBD, rheumatoid arthritis, and multiple sclerosis remain uncommon in less-developed parts of the world where helminthic colonization is still widespread.

Because Dr. Weinstock is a gastroenterologist with a special interest in immunology, his subsequent investigations in animals and humans have focused on IBD.

Initial animal experiments determined that helminth exposure could both prevent and reverse induced colitis in mice by inhibiting inflammatory cytokines such as tumor necrosis factor-β and interleukin (IL)-12 or by promoting the production of regulatory cytokines such as IL-10 and transforming growth factor-β (Int. J. Parasitol. 2007;37:457–64).

In a pilot study of 29 adult patients with longstanding, refractory Crohn's disease, patients were given a drink containing 2,500 specially prepared ova of Trichuris suis, the pig whipworm, every 3 weeks for 24 weeks. Ingestion of this helminth, which is similar to the human whipworm, causes a short-term colonization in the human gastrointestinal tract.

By the 12th week, 22 patients (76%) had responded to the treatment, with a decrease in the Crohn's disease activity index (CDAI) of more than 100 points or below 150, and 19 patients (66%) were in remission, with a CDAI below 150.

At the 24th week, 23 patients (79%) were responders and 21 (72%) were in remission (Gut 2005;54:87–90).

In a subsequent double-blind trial that enrolled 54 adult patients with ulcerative colitis, participants received 2,500 T. suis ova in a liquid drink or a placebo drink every 2 weeks for 12 weeks.

Favorable responses, with decreases in the ulcerative colitis disease activity index of 4 or more points on an index ranging from 0 to 12, were seen in 13 patients receiving the active treatment (43%) compared with 4 receiving placebo (17%).

Similar findings have been shown in several other autoimmune conditions. Prospective data have shown that children with helminths are less likely to develop allergies, and disease has been arrested in patients with multiple sclerosis following helminth colonization. Researchers in the United Kingdom have been investigating modulation of the immune system in rheumatoid arthritis. They tested an anti-inflammatory phosphorylcholine-containing glycoprotein secreted by the nematode Acanthocheilonema viteae in collagen-induced arthritic mice, finding a reduction in the severity of arthritis and suppression of collagen-specific T-1 cytokine production (Ann. Rheum. Dis. 2008;67:518–23).

 

 

Dr. Weinstock believes that helminths and human hosts evolved to the benefit of both over millennia. Petrified human stool many thousands of years old has been found to contain helminth eggs, and autopsies of mummies have found traces of helminths. The frozen iceman Ötzi, found in the northern Italian Alps in 1991 where he had lain buried in a glacier since 3300 B.C., had T. trichiura in his gut.

“We are teeming with life, and we really are part of the environment. When we try to separate ourselves from the environment and exposures to these organisms, we leave ourselves predisposed to disease,” he said.

Dr. Weinstock is not advocating a return to 19th-century hygiene. Rather, he and others are working to characterize more fully the interaction of helminths with the immune system and to identify factors responsible for the beneficial exposures so they can be reintroduced at an appropriate time early in life, when the immune system is developing.

Clinical studies in IBD, asthma, rhinoconjunctivitis, and multiple sclerosis are underway and more are planned, and one helminth-derived medication, ASP1002, is under review by the Food and Drug Administration and the European drug monitoring authorities.

Dr. Francois-Xavier Frapaise, CEO of Asphelia Pharmaceuticals Inc., confirmed that his company is about to file an Investigational New Drug application for ASP1002 in Crohn's disease. They also are planning trials in various other conditions including lupus and multiple sclerosis. “RA would also be interesting to investigate,” he said.

“There has been a revolution in our thinking,” Dr. Weinstock said. “We have learned that we are not insulated from the world around us.”

Helminths, like this whipworm, could be the next big thing in multiple sclerosis and other autoimmune diseases. Courtesy Dr. Joel V. Weinstock

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Think Behçet's When Aphthous Ulcers Recur

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LAKE BUENA VISTA, FLA. — The diagnosis of Behçet's disease must be considered in any patient with recurrent oral and vulvar aphthous ulcers, even if the deep, full-thickness ulcers in the mouth and vulva develop at different times.

Behçet's disease is a chronic inflammatory vasculitis most commonly seen along the ancient silk route from Japan and across Korea, Turkey, and Greece, according to Dr. Andrew T. Goldstein. In the west it occurs most often among young women of Asian or Mediterranean descent.

“This is a bad vasculitis, with complications including dissection of the aorta, blindness, and stroke,” he said.

Aside from the aphthous ulcers, patients with Behçet's disease may have acnelike skin lesions or erythema nodosum as well as ocular, central nervous system, and bowel involvement. The ocular manifestations can be varied and severe, and include iritis, uveitis, and retinal vasculitis. Behçet's disease also can be associated with arthritis and meningitis, and any evidence of this disorder should prompt consultations with ophthalmologists, rheumatologists, and gastroenterologists as symptoms dictate.

“One of the easiest ways of diagnosing Behçet's is the pathergy test,” said Dr. Goldstein.

The pathergy test, in which a 5- to 7-gauge needle is inserted into the forearm, has a very high predictive value, although its negative predictive value is less. If induration develops 24–48 hours later at the site of needle insertion, the test is positive, he said at the annual meeting of the International Pelvic Pain Society.

Although a positive pathergy test is helpful in the diagnosis of Behçet's disease, only a minority of Behçet's patients demonstrate the pathergy phenomenon, according to the Vasculitis Foundation. Patients from the Mediterranean region are more likely to show a positive response, with only 50% of patients in Middle Eastern countries and Japan showing the reaction. A positive reaction is even less common in the United States, and other conditions can occasionally mimic the results (www.vasculitisfoundation.org/pathergytest

Treatments that have been tried for Behçet's disease include conventional immunosuppressives such as azathioprine and corticosteroids; and anti-tumor necrosis factor therapy, particularly with infliximab, according to Dr. Goldstein, who also practices at George Washington University Hospital, Washington. A recent international expert panel suggested that anti-TNF therapy might be suitable for patients with severe, organthreatening disease—patients with two or more relapses of posterior uveitis per year—low visual acuity resulting from chronic cystoid macular edema, or active central nervous system disease (Rheumatology 2007; 46:736–41).

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LAKE BUENA VISTA, FLA. — The diagnosis of Behçet's disease must be considered in any patient with recurrent oral and vulvar aphthous ulcers, even if the deep, full-thickness ulcers in the mouth and vulva develop at different times.

Behçet's disease is a chronic inflammatory vasculitis most commonly seen along the ancient silk route from Japan and across Korea, Turkey, and Greece, according to Dr. Andrew T. Goldstein. In the west it occurs most often among young women of Asian or Mediterranean descent.

“This is a bad vasculitis, with complications including dissection of the aorta, blindness, and stroke,” he said.

Aside from the aphthous ulcers, patients with Behçet's disease may have acnelike skin lesions or erythema nodosum as well as ocular, central nervous system, and bowel involvement. The ocular manifestations can be varied and severe, and include iritis, uveitis, and retinal vasculitis. Behçet's disease also can be associated with arthritis and meningitis, and any evidence of this disorder should prompt consultations with ophthalmologists, rheumatologists, and gastroenterologists as symptoms dictate.

“One of the easiest ways of diagnosing Behçet's is the pathergy test,” said Dr. Goldstein.

The pathergy test, in which a 5- to 7-gauge needle is inserted into the forearm, has a very high predictive value, although its negative predictive value is less. If induration develops 24–48 hours later at the site of needle insertion, the test is positive, he said at the annual meeting of the International Pelvic Pain Society.

Although a positive pathergy test is helpful in the diagnosis of Behçet's disease, only a minority of Behçet's patients demonstrate the pathergy phenomenon, according to the Vasculitis Foundation. Patients from the Mediterranean region are more likely to show a positive response, with only 50% of patients in Middle Eastern countries and Japan showing the reaction. A positive reaction is even less common in the United States, and other conditions can occasionally mimic the results (www.vasculitisfoundation.org/pathergytest

Treatments that have been tried for Behçet's disease include conventional immunosuppressives such as azathioprine and corticosteroids; and anti-tumor necrosis factor therapy, particularly with infliximab, according to Dr. Goldstein, who also practices at George Washington University Hospital, Washington. A recent international expert panel suggested that anti-TNF therapy might be suitable for patients with severe, organthreatening disease—patients with two or more relapses of posterior uveitis per year—low visual acuity resulting from chronic cystoid macular edema, or active central nervous system disease (Rheumatology 2007; 46:736–41).

LAKE BUENA VISTA, FLA. — The diagnosis of Behçet's disease must be considered in any patient with recurrent oral and vulvar aphthous ulcers, even if the deep, full-thickness ulcers in the mouth and vulva develop at different times.

Behçet's disease is a chronic inflammatory vasculitis most commonly seen along the ancient silk route from Japan and across Korea, Turkey, and Greece, according to Dr. Andrew T. Goldstein. In the west it occurs most often among young women of Asian or Mediterranean descent.

“This is a bad vasculitis, with complications including dissection of the aorta, blindness, and stroke,” he said.

Aside from the aphthous ulcers, patients with Behçet's disease may have acnelike skin lesions or erythema nodosum as well as ocular, central nervous system, and bowel involvement. The ocular manifestations can be varied and severe, and include iritis, uveitis, and retinal vasculitis. Behçet's disease also can be associated with arthritis and meningitis, and any evidence of this disorder should prompt consultations with ophthalmologists, rheumatologists, and gastroenterologists as symptoms dictate.

“One of the easiest ways of diagnosing Behçet's is the pathergy test,” said Dr. Goldstein.

The pathergy test, in which a 5- to 7-gauge needle is inserted into the forearm, has a very high predictive value, although its negative predictive value is less. If induration develops 24–48 hours later at the site of needle insertion, the test is positive, he said at the annual meeting of the International Pelvic Pain Society.

Although a positive pathergy test is helpful in the diagnosis of Behçet's disease, only a minority of Behçet's patients demonstrate the pathergy phenomenon, according to the Vasculitis Foundation. Patients from the Mediterranean region are more likely to show a positive response, with only 50% of patients in Middle Eastern countries and Japan showing the reaction. A positive reaction is even less common in the United States, and other conditions can occasionally mimic the results (www.vasculitisfoundation.org/pathergytest

Treatments that have been tried for Behçet's disease include conventional immunosuppressives such as azathioprine and corticosteroids; and anti-tumor necrosis factor therapy, particularly with infliximab, according to Dr. Goldstein, who also practices at George Washington University Hospital, Washington. A recent international expert panel suggested that anti-TNF therapy might be suitable for patients with severe, organthreatening disease—patients with two or more relapses of posterior uveitis per year—low visual acuity resulting from chronic cystoid macular edema, or active central nervous system disease (Rheumatology 2007; 46:736–41).

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LAKE BUENA VISTA, FLA. — Empiric treatment with corticosteroids should be avoided in patients who present with vulvar symptoms such as burning, itching, pain, and dyspareunia, according to Dr. Andrew T. Goldstein.

These patients should have a careful examination of the vulva using a colposcope, and if a lesion is present, a 4-mm punch biopsy is warranted.

When the biopsy specimen is sent to the dermatopathologist, it's important to provide clinical correlates and a differential diagnosis or the result is likely to be simply descriptive rather than diagnostic, said Dr. Goldstein, who is in group practice in Washington.

Patients should know the full name of their disorder, whether lichen sclerosus, lichen simplex chronicus, or erosive lichen planus, Dr. Goldstein said at the annual meeting of the International Pelvic Pain Society.

Lichen sclerosus presents with itching, burning, dyspareunia, and skin texture changes often described as “cigarette paper” skin, with crinkling and fissures around the vulva and anus. Hypopigmentation also is characteristic, with scarring and architectural changes including phimosis of the clitoris, resorption of the labia minora, and narrowing of the introitus causing recurrent tearing. It probably is autoimmune, because patients have a high incidence of other autoimmune diseases, especially thyroid disease.

Lichen sclerosus can develop at any age, including childhood, and is more common than generally appreciated, with a prevalence of 1 in 70 women. But “you have to look for it. The vulva is not just something to separate with a speculum when you do a Pap smear. It has been termed the forgotten pelvic organ.”

Punch biopsy performed before initiating treatment may show hyperkeratosis of the epidermis, epidermal atrophy with loss of rete ridges, homogenization of the collagen in the upper dermis, and a lichenoid inflammatory infiltrate in the dermis. Identifying this condition is critical, as patients with lichen sclerosus have a relative risk of 300 for developing squamous cell carcinoma of the vulva, said Dr. Goldstein, also of George Washington University Hospital, Washington.

Treatment of lichen sclerosus is clobetasol 0.05% ointment once daily after soaking. “I believe the Temovate brand is much better than the generic, probably because of the vehicle,” he said. The corticosteroid should be continued until active disease has resolved, not just for the 2 weeks specified in the package insert.

A second vulvar condition, lichen simplex chronicus, is characterized by thick, lichenified skin of the labia majora and interlabial sulcus, accompanied by erosions, fissuring, and tears in the skin that result from the patient's scratching in her sleep, said Dr. Goldstein. This condition represents the end stage of mast-cell and histamine-mediated itch-scratch-itch cycle in predisposed patients that can be initiated by irritants, allergens, or infections.

All irritants must be stopped, including soaps, detergents, and douches, and underwear must be washed by hand in plain hot water. Daily warm-water sitz baths should be followed by the application of a high-potency topical corticosteroid, which must be rubbed into the skin for 3–4 minutes. Breaking the nocturnal itch-scratch cycle can be accomplished by bedtime amitriptyline, 10–50 mg, and the application of a bag of frozen peas to the vulvar area during the night.

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LAKE BUENA VISTA, FLA. — Empiric treatment with corticosteroids should be avoided in patients who present with vulvar symptoms such as burning, itching, pain, and dyspareunia, according to Dr. Andrew T. Goldstein.

These patients should have a careful examination of the vulva using a colposcope, and if a lesion is present, a 4-mm punch biopsy is warranted.

When the biopsy specimen is sent to the dermatopathologist, it's important to provide clinical correlates and a differential diagnosis or the result is likely to be simply descriptive rather than diagnostic, said Dr. Goldstein, who is in group practice in Washington.

Patients should know the full name of their disorder, whether lichen sclerosus, lichen simplex chronicus, or erosive lichen planus, Dr. Goldstein said at the annual meeting of the International Pelvic Pain Society.

Lichen sclerosus presents with itching, burning, dyspareunia, and skin texture changes often described as “cigarette paper” skin, with crinkling and fissures around the vulva and anus. Hypopigmentation also is characteristic, with scarring and architectural changes including phimosis of the clitoris, resorption of the labia minora, and narrowing of the introitus causing recurrent tearing. It probably is autoimmune, because patients have a high incidence of other autoimmune diseases, especially thyroid disease.

Lichen sclerosus can develop at any age, including childhood, and is more common than generally appreciated, with a prevalence of 1 in 70 women. But “you have to look for it. The vulva is not just something to separate with a speculum when you do a Pap smear. It has been termed the forgotten pelvic organ.”

Punch biopsy performed before initiating treatment may show hyperkeratosis of the epidermis, epidermal atrophy with loss of rete ridges, homogenization of the collagen in the upper dermis, and a lichenoid inflammatory infiltrate in the dermis. Identifying this condition is critical, as patients with lichen sclerosus have a relative risk of 300 for developing squamous cell carcinoma of the vulva, said Dr. Goldstein, also of George Washington University Hospital, Washington.

Treatment of lichen sclerosus is clobetasol 0.05% ointment once daily after soaking. “I believe the Temovate brand is much better than the generic, probably because of the vehicle,” he said. The corticosteroid should be continued until active disease has resolved, not just for the 2 weeks specified in the package insert.

A second vulvar condition, lichen simplex chronicus, is characterized by thick, lichenified skin of the labia majora and interlabial sulcus, accompanied by erosions, fissuring, and tears in the skin that result from the patient's scratching in her sleep, said Dr. Goldstein. This condition represents the end stage of mast-cell and histamine-mediated itch-scratch-itch cycle in predisposed patients that can be initiated by irritants, allergens, or infections.

All irritants must be stopped, including soaps, detergents, and douches, and underwear must be washed by hand in plain hot water. Daily warm-water sitz baths should be followed by the application of a high-potency topical corticosteroid, which must be rubbed into the skin for 3–4 minutes. Breaking the nocturnal itch-scratch cycle can be accomplished by bedtime amitriptyline, 10–50 mg, and the application of a bag of frozen peas to the vulvar area during the night.

LAKE BUENA VISTA, FLA. — Empiric treatment with corticosteroids should be avoided in patients who present with vulvar symptoms such as burning, itching, pain, and dyspareunia, according to Dr. Andrew T. Goldstein.

These patients should have a careful examination of the vulva using a colposcope, and if a lesion is present, a 4-mm punch biopsy is warranted.

When the biopsy specimen is sent to the dermatopathologist, it's important to provide clinical correlates and a differential diagnosis or the result is likely to be simply descriptive rather than diagnostic, said Dr. Goldstein, who is in group practice in Washington.

Patients should know the full name of their disorder, whether lichen sclerosus, lichen simplex chronicus, or erosive lichen planus, Dr. Goldstein said at the annual meeting of the International Pelvic Pain Society.

Lichen sclerosus presents with itching, burning, dyspareunia, and skin texture changes often described as “cigarette paper” skin, with crinkling and fissures around the vulva and anus. Hypopigmentation also is characteristic, with scarring and architectural changes including phimosis of the clitoris, resorption of the labia minora, and narrowing of the introitus causing recurrent tearing. It probably is autoimmune, because patients have a high incidence of other autoimmune diseases, especially thyroid disease.

Lichen sclerosus can develop at any age, including childhood, and is more common than generally appreciated, with a prevalence of 1 in 70 women. But “you have to look for it. The vulva is not just something to separate with a speculum when you do a Pap smear. It has been termed the forgotten pelvic organ.”

Punch biopsy performed before initiating treatment may show hyperkeratosis of the epidermis, epidermal atrophy with loss of rete ridges, homogenization of the collagen in the upper dermis, and a lichenoid inflammatory infiltrate in the dermis. Identifying this condition is critical, as patients with lichen sclerosus have a relative risk of 300 for developing squamous cell carcinoma of the vulva, said Dr. Goldstein, also of George Washington University Hospital, Washington.

Treatment of lichen sclerosus is clobetasol 0.05% ointment once daily after soaking. “I believe the Temovate brand is much better than the generic, probably because of the vehicle,” he said. The corticosteroid should be continued until active disease has resolved, not just for the 2 weeks specified in the package insert.

A second vulvar condition, lichen simplex chronicus, is characterized by thick, lichenified skin of the labia majora and interlabial sulcus, accompanied by erosions, fissuring, and tears in the skin that result from the patient's scratching in her sleep, said Dr. Goldstein. This condition represents the end stage of mast-cell and histamine-mediated itch-scratch-itch cycle in predisposed patients that can be initiated by irritants, allergens, or infections.

All irritants must be stopped, including soaps, detergents, and douches, and underwear must be washed by hand in plain hot water. Daily warm-water sitz baths should be followed by the application of a high-potency topical corticosteroid, which must be rubbed into the skin for 3–4 minutes. Breaking the nocturnal itch-scratch cycle can be accomplished by bedtime amitriptyline, 10–50 mg, and the application of a bag of frozen peas to the vulvar area during the night.

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Avoid Empiric Steroid Treatment for Vulvar Skin Disorders

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LAKE BUENA VISTA, FLA.—Empiric treatment with corticosteroids should be avoided in patients who present with vulvar symptoms such as burning, itching, pain, and dyspareunia, according to one researcher who specializes in the subject area.

These patients should have a careful examination of the vulva using a colposcope, and if a lesion is present, a 4-mm punch biopsy is warranted.

When the biopsy specimen is sent to the dermatopathologist, it's important to provide clinical correlates and a differential diagnosis or the result is likely to be simply descriptive—acanthosis, hyperkeratosis, chronic inflammation—rather than diagnostic, Dr. Andrew T. Goldstein said at the annual meeting of the International Pelvic Pain Society.

And be sure patients understand that all lichens are not created equal, and they need to know the full name of their disorder, whether lichen sclerosus, lichen simplex chronicus, or erosive lichen planus.

Lichen Sclerosus

Lichen sclerosus typically presents with itching, burning, dyspareunia, and skin texture changes often described as “cigarette paper” skin, with crinkling and fissures around the vulva and anus. Hypopigmentation also is characteristic, with scarring and architectural changes including phimosis of the clitoris, resorption of the labia minora, and narrowing of the introitus causing recurrent tearing.

This condition probably is autoimmune, he said, with a proliferation of monoclonal T cells in the dermis and high levels of circulating autoantibodies. Patients with lichen sclerosus also have a high incidence of other autoimmune diseases, especially thyroid disease.

Lichen sclerosus can develop at any age, including childhood, and is more common than generally appreciated, with a prevalence of 1 in 70 women. “As a busy gynecologist you may be seeing lichen sclerosus once or twice a week, but only diagnosing it once or twice a year,” he said. “You have to look for it. The vulva is not just something to separate with a speculum when you do a Pap smear. It has been termed the forgotten pelvic organ.”

Punch biopsy performed before initiating treatment may show hyperkeratosis of the epidermis, epidermal atrophy with loss of rete ridges, homogenization of the collagen in the upper dermis, and a lichenoid inflammatory infiltrate in the dermis. Identifying this condition is critical, as patients with lichen sclerosus have a relative risk of 300 for developing squamous cell carcinoma of the vulva, said Dr. Goldstein of George Washington University Hospital, Washington.

Treatment of lichen sclerosus is clobetasol 0.05% ointment once daily after soaking. “I believe the Temovate brand is much better than the generic, probably because of the vehicle,” he said. The corticosteroid should be continued until active disease has resolved, not just for the 2 weeks specified in the package insert, and then the frequency and potency can be reduced.

Testosterone propionate should not be used. “If a patient with lichen sclerosus develops squamous cell carcinoma and was treated with testosterone, I'll be more than happy to testify for the plaintiff because 17 years ago it was shown to be no better than placebo,” he said.

Lichen Simplex Chronicus

A second vulvar condition, lichen simplex chronicus, is characterized by thick, lichenified skin of the labia majora and interlabial sulcus, accompanied by erosions, fissuring, and tears in the skin that result from the patient's scratching in her sleep, said Dr. Goldstein.

This condition represents the end stage of mast-cell and histamine-mediated itch-scratch-itch cycle in predisposed patients that can be initiated by irritants, allergens, or infections.

All irritants such as soaps, detergents, and douches must be stopped, and underwear must be washed by hand in plain hot water. Daily warm-water sitz baths should be followed by application of a high-potency topical corticosteroid, which must be rubbed into the skin for 3–4 minutes.

Breaking the nocturnal itch-scratch cycle can be accomplished by bedtime amitriptyline, 10–50 mg, and the application of a bag of frozen peas to the vulvar area during the night.

An investigational alternative to topical corticosteroids is topical pimecrolimus, which is not associated with dermal atrophy. This agent showed promise in an open-label preliminary trial that included 12 women aged 25–53 years, according to Dr. Goldstein, who was the lead investigator and who disclosed that he has received grants and research support from Novartis, the manufacturer of pimecrolimus.

In this study, patients applied pimecrolimus cream 1% twice daily. Median pruritus scores decreased at weeks 4, 8, and 12, and seven patients reported complete resolution of pruritus by week 4 (Gynecol. Obstet. Invest. 2007;64:180-6).

Erosive Lichen Planus

A third vulvar disorder to watch for is erosive lichen planus, which is associated with burning and severe dyspareunia and is characterized by red plaques with white “lacy” edges (Wickham's striae). Vulvar and vaginal lesions also can be accompanied by lesions of the oral mucosa.

 

 

This condition can be somewhat more difficult to treat, starting with topical corticosteroids or macrolide immunosuppressants, but oral agents such as steroids, retinoids, and other immunosuppressants also are often required. Vaginal dilators also are essential, to prevent scarring that can occur within a matter of weeks, he said.

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LAKE BUENA VISTA, FLA.—Empiric treatment with corticosteroids should be avoided in patients who present with vulvar symptoms such as burning, itching, pain, and dyspareunia, according to one researcher who specializes in the subject area.

These patients should have a careful examination of the vulva using a colposcope, and if a lesion is present, a 4-mm punch biopsy is warranted.

When the biopsy specimen is sent to the dermatopathologist, it's important to provide clinical correlates and a differential diagnosis or the result is likely to be simply descriptive—acanthosis, hyperkeratosis, chronic inflammation—rather than diagnostic, Dr. Andrew T. Goldstein said at the annual meeting of the International Pelvic Pain Society.

And be sure patients understand that all lichens are not created equal, and they need to know the full name of their disorder, whether lichen sclerosus, lichen simplex chronicus, or erosive lichen planus.

Lichen Sclerosus

Lichen sclerosus typically presents with itching, burning, dyspareunia, and skin texture changes often described as “cigarette paper” skin, with crinkling and fissures around the vulva and anus. Hypopigmentation also is characteristic, with scarring and architectural changes including phimosis of the clitoris, resorption of the labia minora, and narrowing of the introitus causing recurrent tearing.

This condition probably is autoimmune, he said, with a proliferation of monoclonal T cells in the dermis and high levels of circulating autoantibodies. Patients with lichen sclerosus also have a high incidence of other autoimmune diseases, especially thyroid disease.

Lichen sclerosus can develop at any age, including childhood, and is more common than generally appreciated, with a prevalence of 1 in 70 women. “As a busy gynecologist you may be seeing lichen sclerosus once or twice a week, but only diagnosing it once or twice a year,” he said. “You have to look for it. The vulva is not just something to separate with a speculum when you do a Pap smear. It has been termed the forgotten pelvic organ.”

Punch biopsy performed before initiating treatment may show hyperkeratosis of the epidermis, epidermal atrophy with loss of rete ridges, homogenization of the collagen in the upper dermis, and a lichenoid inflammatory infiltrate in the dermis. Identifying this condition is critical, as patients with lichen sclerosus have a relative risk of 300 for developing squamous cell carcinoma of the vulva, said Dr. Goldstein of George Washington University Hospital, Washington.

Treatment of lichen sclerosus is clobetasol 0.05% ointment once daily after soaking. “I believe the Temovate brand is much better than the generic, probably because of the vehicle,” he said. The corticosteroid should be continued until active disease has resolved, not just for the 2 weeks specified in the package insert, and then the frequency and potency can be reduced.

Testosterone propionate should not be used. “If a patient with lichen sclerosus develops squamous cell carcinoma and was treated with testosterone, I'll be more than happy to testify for the plaintiff because 17 years ago it was shown to be no better than placebo,” he said.

Lichen Simplex Chronicus

A second vulvar condition, lichen simplex chronicus, is characterized by thick, lichenified skin of the labia majora and interlabial sulcus, accompanied by erosions, fissuring, and tears in the skin that result from the patient's scratching in her sleep, said Dr. Goldstein.

This condition represents the end stage of mast-cell and histamine-mediated itch-scratch-itch cycle in predisposed patients that can be initiated by irritants, allergens, or infections.

All irritants such as soaps, detergents, and douches must be stopped, and underwear must be washed by hand in plain hot water. Daily warm-water sitz baths should be followed by application of a high-potency topical corticosteroid, which must be rubbed into the skin for 3–4 minutes.

Breaking the nocturnal itch-scratch cycle can be accomplished by bedtime amitriptyline, 10–50 mg, and the application of a bag of frozen peas to the vulvar area during the night.

An investigational alternative to topical corticosteroids is topical pimecrolimus, which is not associated with dermal atrophy. This agent showed promise in an open-label preliminary trial that included 12 women aged 25–53 years, according to Dr. Goldstein, who was the lead investigator and who disclosed that he has received grants and research support from Novartis, the manufacturer of pimecrolimus.

In this study, patients applied pimecrolimus cream 1% twice daily. Median pruritus scores decreased at weeks 4, 8, and 12, and seven patients reported complete resolution of pruritus by week 4 (Gynecol. Obstet. Invest. 2007;64:180-6).

Erosive Lichen Planus

A third vulvar disorder to watch for is erosive lichen planus, which is associated with burning and severe dyspareunia and is characterized by red plaques with white “lacy” edges (Wickham's striae). Vulvar and vaginal lesions also can be accompanied by lesions of the oral mucosa.

 

 

This condition can be somewhat more difficult to treat, starting with topical corticosteroids or macrolide immunosuppressants, but oral agents such as steroids, retinoids, and other immunosuppressants also are often required. Vaginal dilators also are essential, to prevent scarring that can occur within a matter of weeks, he said.

LAKE BUENA VISTA, FLA.—Empiric treatment with corticosteroids should be avoided in patients who present with vulvar symptoms such as burning, itching, pain, and dyspareunia, according to one researcher who specializes in the subject area.

These patients should have a careful examination of the vulva using a colposcope, and if a lesion is present, a 4-mm punch biopsy is warranted.

When the biopsy specimen is sent to the dermatopathologist, it's important to provide clinical correlates and a differential diagnosis or the result is likely to be simply descriptive—acanthosis, hyperkeratosis, chronic inflammation—rather than diagnostic, Dr. Andrew T. Goldstein said at the annual meeting of the International Pelvic Pain Society.

And be sure patients understand that all lichens are not created equal, and they need to know the full name of their disorder, whether lichen sclerosus, lichen simplex chronicus, or erosive lichen planus.

Lichen Sclerosus

Lichen sclerosus typically presents with itching, burning, dyspareunia, and skin texture changes often described as “cigarette paper” skin, with crinkling and fissures around the vulva and anus. Hypopigmentation also is characteristic, with scarring and architectural changes including phimosis of the clitoris, resorption of the labia minora, and narrowing of the introitus causing recurrent tearing.

This condition probably is autoimmune, he said, with a proliferation of monoclonal T cells in the dermis and high levels of circulating autoantibodies. Patients with lichen sclerosus also have a high incidence of other autoimmune diseases, especially thyroid disease.

Lichen sclerosus can develop at any age, including childhood, and is more common than generally appreciated, with a prevalence of 1 in 70 women. “As a busy gynecologist you may be seeing lichen sclerosus once or twice a week, but only diagnosing it once or twice a year,” he said. “You have to look for it. The vulva is not just something to separate with a speculum when you do a Pap smear. It has been termed the forgotten pelvic organ.”

Punch biopsy performed before initiating treatment may show hyperkeratosis of the epidermis, epidermal atrophy with loss of rete ridges, homogenization of the collagen in the upper dermis, and a lichenoid inflammatory infiltrate in the dermis. Identifying this condition is critical, as patients with lichen sclerosus have a relative risk of 300 for developing squamous cell carcinoma of the vulva, said Dr. Goldstein of George Washington University Hospital, Washington.

Treatment of lichen sclerosus is clobetasol 0.05% ointment once daily after soaking. “I believe the Temovate brand is much better than the generic, probably because of the vehicle,” he said. The corticosteroid should be continued until active disease has resolved, not just for the 2 weeks specified in the package insert, and then the frequency and potency can be reduced.

Testosterone propionate should not be used. “If a patient with lichen sclerosus develops squamous cell carcinoma and was treated with testosterone, I'll be more than happy to testify for the plaintiff because 17 years ago it was shown to be no better than placebo,” he said.

Lichen Simplex Chronicus

A second vulvar condition, lichen simplex chronicus, is characterized by thick, lichenified skin of the labia majora and interlabial sulcus, accompanied by erosions, fissuring, and tears in the skin that result from the patient's scratching in her sleep, said Dr. Goldstein.

This condition represents the end stage of mast-cell and histamine-mediated itch-scratch-itch cycle in predisposed patients that can be initiated by irritants, allergens, or infections.

All irritants such as soaps, detergents, and douches must be stopped, and underwear must be washed by hand in plain hot water. Daily warm-water sitz baths should be followed by application of a high-potency topical corticosteroid, which must be rubbed into the skin for 3–4 minutes.

Breaking the nocturnal itch-scratch cycle can be accomplished by bedtime amitriptyline, 10–50 mg, and the application of a bag of frozen peas to the vulvar area during the night.

An investigational alternative to topical corticosteroids is topical pimecrolimus, which is not associated with dermal atrophy. This agent showed promise in an open-label preliminary trial that included 12 women aged 25–53 years, according to Dr. Goldstein, who was the lead investigator and who disclosed that he has received grants and research support from Novartis, the manufacturer of pimecrolimus.

In this study, patients applied pimecrolimus cream 1% twice daily. Median pruritus scores decreased at weeks 4, 8, and 12, and seven patients reported complete resolution of pruritus by week 4 (Gynecol. Obstet. Invest. 2007;64:180-6).

Erosive Lichen Planus

A third vulvar disorder to watch for is erosive lichen planus, which is associated with burning and severe dyspareunia and is characterized by red plaques with white “lacy” edges (Wickham's striae). Vulvar and vaginal lesions also can be accompanied by lesions of the oral mucosa.

 

 

This condition can be somewhat more difficult to treat, starting with topical corticosteroids or macrolide immunosuppressants, but oral agents such as steroids, retinoids, and other immunosuppressants also are often required. Vaginal dilators also are essential, to prevent scarring that can occur within a matter of weeks, he said.

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Common Dermatologic Surgery Beliefs Dispelled by Expert

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PALM BEACH, FLA. — Certain widely held beliefs among dermatologic surgeons are revealed as myths when subjected to scientific scrutiny, according to Dr. James M. Spencer.

"In surgery we do a lot of things just because a respected professor once told us to," said Dr. Spencer of Mount Sinai School of Medicine, New York.

An example Dr. Spencer cited is the dictum that one should never use epinephrine with lidocaine on the fingers, because the epinephrine is so vasoconstrictive that hypoxia and necrosis would result. This prohibition is included as dogma in textbooks—yet a literature review identified only 50 reported cases of digital gangrene following local anesthesia. All of these were early 20th century cases and multiple medications were involved, including cocaine and procaine, with nonstandardized techniques and methods of mixing, he said.

These early cases also included the inappropriate use of tourniquets and postoperative hot soaks (J. Am. Acad. Dermatol. 2004;51:755–9). There have been no reports of necrosis of the finger since commercial lidocaine with epinephrine was introduced in 1948, Dr. Spencer said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Another myth is that dog-ears must be completely removed at the time of surgery or they will be permanent. "I was taught 'thou shalt not leave dog-ears,' but this is clearly untrue," he said.

"When I had my first job at the University of Miami, the chairman of the department of plastic surgery would do primary repairs leaving patients with dog-ears. I wondered why no one had ever told him not to leave dog-ears, but then I thought, what are the chances of me being right and the chairman of plastic surgery being wrong? Zero," he said.

When this was studied prospectively, in 43 postexcision dog-ears in 26 patients, some degree of regression was seen in all 43. The dog-ears were measured immediately postoperatively and followed for up to 180 days. Complete regression was seen in 19 of the 43, over a mean of 132 days, and the probability of complete regression was greater in dog-ears of 8 mm in height or less (Dermatol. Surg. 2008;34:1070–6).

"I can tell you from experience that dog-ears on hands regress completely, those on arms and legs do pretty well, but those on the forehead not at all," he said.

"We also were all taught that nonabsorbable sutures are always preferred as outer, cuticular sutures because absorbable sutures are too inflammatory, they favor infection, and give an inferior cosmetic result," he said.

Patients, however, would prefer not to have to return for suture removal, so a group of emergency physicians performed a study in which they randomized pediatric patients with lacerations to treatment with absorbable plain gut sutures or nonabsorbable nylon sutures and evaluated them at 10 days and at 4–5 months.

At 10-day follow-up, there were no differences in wound outcome, including infection and dehiscence rates, and 4–5 months later, evaluation by a blinded plastic surgeon showed no difference in cosmetic outcome (Acad. Emerg. Med. 2004;11:730–5). "In fact, the plain gut sutures appeared to give a slightly better cosmetic result," said Dr. Spencer, who also is in private practice in St. Petersburg, Fla.

Another myth that has been perpetuated by dermatologists is that patients receive 80% of their lifetime sun exposure by age 18.

The 80% number was an extrapolation from a calculation in 1986 that sunscreen use by young people would reduce their lifetime risk of skin cancer by 78%. In fact, the original publication stated that the incidence of nonmelanoma skin cancer was related to the square of the ultraviolet dose—the actual dose was not calculated (Arch. Derm. 1986;122:537–45).

A more recent analysis determined that Americans actually receive less than 25% of their total exposure by age 18 (Photochem. Photobiol. 2003;77:453–7). "This, of course, means that sun protection is equally important in older and younger patients," he said.

Finally, it has been accepted that laser resurfacing is contraindicated while a patient is on isotretinoin, but there is very little evidence to support this, with only nine cases of keloid scarring having been reported. Six were from Dr. Henry Roenigk in Chicago, who has done thousands of cases of dermabrasion on patients with acne scars who were on isotretinoin or had only recently discontinued it (J. Am. Acad. Dermatol. 1986;15:280–5). The remaining three were patients from Great Britain who developed scarring after dermabrasion or argon laser while taking isotretinoin (Br. J. Dermatol. 1988;118:703–6).

"That's it. Nine patients in the world literature have become a medicolegal fact. Textbooks don't even reference it, they just state it like it's the 11th commandment."

 

 

Dr. Spencer disclosed having no conflicts of interest relevant to his presenation.

'I was taught "thou shalt not leave dog-ears," but this is clearly untrue.' DR. SPENCER

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PALM BEACH, FLA. — Certain widely held beliefs among dermatologic surgeons are revealed as myths when subjected to scientific scrutiny, according to Dr. James M. Spencer.

"In surgery we do a lot of things just because a respected professor once told us to," said Dr. Spencer of Mount Sinai School of Medicine, New York.

An example Dr. Spencer cited is the dictum that one should never use epinephrine with lidocaine on the fingers, because the epinephrine is so vasoconstrictive that hypoxia and necrosis would result. This prohibition is included as dogma in textbooks—yet a literature review identified only 50 reported cases of digital gangrene following local anesthesia. All of these were early 20th century cases and multiple medications were involved, including cocaine and procaine, with nonstandardized techniques and methods of mixing, he said.

These early cases also included the inappropriate use of tourniquets and postoperative hot soaks (J. Am. Acad. Dermatol. 2004;51:755–9). There have been no reports of necrosis of the finger since commercial lidocaine with epinephrine was introduced in 1948, Dr. Spencer said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Another myth is that dog-ears must be completely removed at the time of surgery or they will be permanent. "I was taught 'thou shalt not leave dog-ears,' but this is clearly untrue," he said.

"When I had my first job at the University of Miami, the chairman of the department of plastic surgery would do primary repairs leaving patients with dog-ears. I wondered why no one had ever told him not to leave dog-ears, but then I thought, what are the chances of me being right and the chairman of plastic surgery being wrong? Zero," he said.

When this was studied prospectively, in 43 postexcision dog-ears in 26 patients, some degree of regression was seen in all 43. The dog-ears were measured immediately postoperatively and followed for up to 180 days. Complete regression was seen in 19 of the 43, over a mean of 132 days, and the probability of complete regression was greater in dog-ears of 8 mm in height or less (Dermatol. Surg. 2008;34:1070–6).

"I can tell you from experience that dog-ears on hands regress completely, those on arms and legs do pretty well, but those on the forehead not at all," he said.

"We also were all taught that nonabsorbable sutures are always preferred as outer, cuticular sutures because absorbable sutures are too inflammatory, they favor infection, and give an inferior cosmetic result," he said.

Patients, however, would prefer not to have to return for suture removal, so a group of emergency physicians performed a study in which they randomized pediatric patients with lacerations to treatment with absorbable plain gut sutures or nonabsorbable nylon sutures and evaluated them at 10 days and at 4–5 months.

At 10-day follow-up, there were no differences in wound outcome, including infection and dehiscence rates, and 4–5 months later, evaluation by a blinded plastic surgeon showed no difference in cosmetic outcome (Acad. Emerg. Med. 2004;11:730–5). "In fact, the plain gut sutures appeared to give a slightly better cosmetic result," said Dr. Spencer, who also is in private practice in St. Petersburg, Fla.

Another myth that has been perpetuated by dermatologists is that patients receive 80% of their lifetime sun exposure by age 18.

The 80% number was an extrapolation from a calculation in 1986 that sunscreen use by young people would reduce their lifetime risk of skin cancer by 78%. In fact, the original publication stated that the incidence of nonmelanoma skin cancer was related to the square of the ultraviolet dose—the actual dose was not calculated (Arch. Derm. 1986;122:537–45).

A more recent analysis determined that Americans actually receive less than 25% of their total exposure by age 18 (Photochem. Photobiol. 2003;77:453–7). "This, of course, means that sun protection is equally important in older and younger patients," he said.

Finally, it has been accepted that laser resurfacing is contraindicated while a patient is on isotretinoin, but there is very little evidence to support this, with only nine cases of keloid scarring having been reported. Six were from Dr. Henry Roenigk in Chicago, who has done thousands of cases of dermabrasion on patients with acne scars who were on isotretinoin or had only recently discontinued it (J. Am. Acad. Dermatol. 1986;15:280–5). The remaining three were patients from Great Britain who developed scarring after dermabrasion or argon laser while taking isotretinoin (Br. J. Dermatol. 1988;118:703–6).

"That's it. Nine patients in the world literature have become a medicolegal fact. Textbooks don't even reference it, they just state it like it's the 11th commandment."

 

 

Dr. Spencer disclosed having no conflicts of interest relevant to his presenation.

'I was taught "thou shalt not leave dog-ears," but this is clearly untrue.' DR. SPENCER

PALM BEACH, FLA. — Certain widely held beliefs among dermatologic surgeons are revealed as myths when subjected to scientific scrutiny, according to Dr. James M. Spencer.

"In surgery we do a lot of things just because a respected professor once told us to," said Dr. Spencer of Mount Sinai School of Medicine, New York.

An example Dr. Spencer cited is the dictum that one should never use epinephrine with lidocaine on the fingers, because the epinephrine is so vasoconstrictive that hypoxia and necrosis would result. This prohibition is included as dogma in textbooks—yet a literature review identified only 50 reported cases of digital gangrene following local anesthesia. All of these were early 20th century cases and multiple medications were involved, including cocaine and procaine, with nonstandardized techniques and methods of mixing, he said.

These early cases also included the inappropriate use of tourniquets and postoperative hot soaks (J. Am. Acad. Dermatol. 2004;51:755–9). There have been no reports of necrosis of the finger since commercial lidocaine with epinephrine was introduced in 1948, Dr. Spencer said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Another myth is that dog-ears must be completely removed at the time of surgery or they will be permanent. "I was taught 'thou shalt not leave dog-ears,' but this is clearly untrue," he said.

"When I had my first job at the University of Miami, the chairman of the department of plastic surgery would do primary repairs leaving patients with dog-ears. I wondered why no one had ever told him not to leave dog-ears, but then I thought, what are the chances of me being right and the chairman of plastic surgery being wrong? Zero," he said.

When this was studied prospectively, in 43 postexcision dog-ears in 26 patients, some degree of regression was seen in all 43. The dog-ears were measured immediately postoperatively and followed for up to 180 days. Complete regression was seen in 19 of the 43, over a mean of 132 days, and the probability of complete regression was greater in dog-ears of 8 mm in height or less (Dermatol. Surg. 2008;34:1070–6).

"I can tell you from experience that dog-ears on hands regress completely, those on arms and legs do pretty well, but those on the forehead not at all," he said.

"We also were all taught that nonabsorbable sutures are always preferred as outer, cuticular sutures because absorbable sutures are too inflammatory, they favor infection, and give an inferior cosmetic result," he said.

Patients, however, would prefer not to have to return for suture removal, so a group of emergency physicians performed a study in which they randomized pediatric patients with lacerations to treatment with absorbable plain gut sutures or nonabsorbable nylon sutures and evaluated them at 10 days and at 4–5 months.

At 10-day follow-up, there were no differences in wound outcome, including infection and dehiscence rates, and 4–5 months later, evaluation by a blinded plastic surgeon showed no difference in cosmetic outcome (Acad. Emerg. Med. 2004;11:730–5). "In fact, the plain gut sutures appeared to give a slightly better cosmetic result," said Dr. Spencer, who also is in private practice in St. Petersburg, Fla.

Another myth that has been perpetuated by dermatologists is that patients receive 80% of their lifetime sun exposure by age 18.

The 80% number was an extrapolation from a calculation in 1986 that sunscreen use by young people would reduce their lifetime risk of skin cancer by 78%. In fact, the original publication stated that the incidence of nonmelanoma skin cancer was related to the square of the ultraviolet dose—the actual dose was not calculated (Arch. Derm. 1986;122:537–45).

A more recent analysis determined that Americans actually receive less than 25% of their total exposure by age 18 (Photochem. Photobiol. 2003;77:453–7). "This, of course, means that sun protection is equally important in older and younger patients," he said.

Finally, it has been accepted that laser resurfacing is contraindicated while a patient is on isotretinoin, but there is very little evidence to support this, with only nine cases of keloid scarring having been reported. Six were from Dr. Henry Roenigk in Chicago, who has done thousands of cases of dermabrasion on patients with acne scars who were on isotretinoin or had only recently discontinued it (J. Am. Acad. Dermatol. 1986;15:280–5). The remaining three were patients from Great Britain who developed scarring after dermabrasion or argon laser while taking isotretinoin (Br. J. Dermatol. 1988;118:703–6).

"That's it. Nine patients in the world literature have become a medicolegal fact. Textbooks don't even reference it, they just state it like it's the 11th commandment."

 

 

Dr. Spencer disclosed having no conflicts of interest relevant to his presenation.

'I was taught "thou shalt not leave dog-ears," but this is clearly untrue.' DR. SPENCER

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Purse-String Closure Best Choice for Difficult Cases

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PALM BEACH, FLA. — Purse-string closure is a useful technique for difficult postsurgical cases in patients who cannot tolerate long procedures or who have difficulty with follow-up, according to Dr. John Robert Hamill Jr.

This technique also minimizes scarring, especially in areas of high tension or thin skin, with the final scar almost always being significantly smaller than the original defect, Dr. Hamill said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Purse-string closure of defects after surgery for skin cancer—with sutures placed around the defect and the skin pulled together—is cost effective. "I charge for intermediate closure for this procedure, eliminating the need for flaps, grafts, and multiple staged procedures," said Dr. Hamill of the department of dermatology and cutaneous surgery at the University of South Florida, Tampa.

For example, this was suitable for an elderly nursing home patient with malignant melanoma in situ on the left lower arm (see images above).

"The patient had multiple medical problems, and both she and her daughter wanted almost no surgery, so I did the simplest thing I could," said Dr. Hamill, director of the advanced dermatology surgery clinic at James A. Haley Veterans' Hospital, Tampa, and medical director at Gulf Coast Dermatology, Hudson, Fla.

The original 2.8-by-2.9-cm defect was closed with nylon skin sutures at the concentric redundant skin folds, and the final 0.7-by-0.5-cm defect left to granulate. "The skin here is bunchy, but in this type of patient you can get away with that because the skin is so loose. The puffiness will go down," he said.

Two months later, there was a small amount of breakdown and granulation tissue in the center of the defect, which was debrided in standard fashion with curetting, electrocautery, and topical aluminum chloride. Once the crust was scraped off the dermis was perfect, Dr. Hamill said at the meeting.

Because of the patient's complex medical problems she was unable to return for further follow-up, but a phone call to the nursing home determined that she was "perfectly healed and perfectly happy," he said.

"This is the type of surgery I would want my own grandmother to have because of its simplicity and lack of complications," he said.

The main disadvantages of the purse-string closure are the marked distortion of the skin immediately following the surgery and the possibility that simple scar revision may be needed in areas of high tension. But with a careful preoperative discussion, and the patient's being shown photos of other patients' outcomes, these are generally not major problems.

"In general, my patients have been extremely happy with this technique," Dr. Hamill concluded.

The lower left arm of the elderly nursing home patient with malignant melanoma in situ is shown before excision (left); immediately following excision (middle); and 2 weeks after surgery (right). The patient was "perfectly healed" and happy. Photos courtesy Dr. John Robert Hamill Jr.

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PALM BEACH, FLA. — Purse-string closure is a useful technique for difficult postsurgical cases in patients who cannot tolerate long procedures or who have difficulty with follow-up, according to Dr. John Robert Hamill Jr.

This technique also minimizes scarring, especially in areas of high tension or thin skin, with the final scar almost always being significantly smaller than the original defect, Dr. Hamill said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Purse-string closure of defects after surgery for skin cancer—with sutures placed around the defect and the skin pulled together—is cost effective. "I charge for intermediate closure for this procedure, eliminating the need for flaps, grafts, and multiple staged procedures," said Dr. Hamill of the department of dermatology and cutaneous surgery at the University of South Florida, Tampa.

For example, this was suitable for an elderly nursing home patient with malignant melanoma in situ on the left lower arm (see images above).

"The patient had multiple medical problems, and both she and her daughter wanted almost no surgery, so I did the simplest thing I could," said Dr. Hamill, director of the advanced dermatology surgery clinic at James A. Haley Veterans' Hospital, Tampa, and medical director at Gulf Coast Dermatology, Hudson, Fla.

The original 2.8-by-2.9-cm defect was closed with nylon skin sutures at the concentric redundant skin folds, and the final 0.7-by-0.5-cm defect left to granulate. "The skin here is bunchy, but in this type of patient you can get away with that because the skin is so loose. The puffiness will go down," he said.

Two months later, there was a small amount of breakdown and granulation tissue in the center of the defect, which was debrided in standard fashion with curetting, electrocautery, and topical aluminum chloride. Once the crust was scraped off the dermis was perfect, Dr. Hamill said at the meeting.

Because of the patient's complex medical problems she was unable to return for further follow-up, but a phone call to the nursing home determined that she was "perfectly healed and perfectly happy," he said.

"This is the type of surgery I would want my own grandmother to have because of its simplicity and lack of complications," he said.

The main disadvantages of the purse-string closure are the marked distortion of the skin immediately following the surgery and the possibility that simple scar revision may be needed in areas of high tension. But with a careful preoperative discussion, and the patient's being shown photos of other patients' outcomes, these are generally not major problems.

"In general, my patients have been extremely happy with this technique," Dr. Hamill concluded.

The lower left arm of the elderly nursing home patient with malignant melanoma in situ is shown before excision (left); immediately following excision (middle); and 2 weeks after surgery (right). The patient was "perfectly healed" and happy. Photos courtesy Dr. John Robert Hamill Jr.

PALM BEACH, FLA. — Purse-string closure is a useful technique for difficult postsurgical cases in patients who cannot tolerate long procedures or who have difficulty with follow-up, according to Dr. John Robert Hamill Jr.

This technique also minimizes scarring, especially in areas of high tension or thin skin, with the final scar almost always being significantly smaller than the original defect, Dr. Hamill said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Purse-string closure of defects after surgery for skin cancer—with sutures placed around the defect and the skin pulled together—is cost effective. "I charge for intermediate closure for this procedure, eliminating the need for flaps, grafts, and multiple staged procedures," said Dr. Hamill of the department of dermatology and cutaneous surgery at the University of South Florida, Tampa.

For example, this was suitable for an elderly nursing home patient with malignant melanoma in situ on the left lower arm (see images above).

"The patient had multiple medical problems, and both she and her daughter wanted almost no surgery, so I did the simplest thing I could," said Dr. Hamill, director of the advanced dermatology surgery clinic at James A. Haley Veterans' Hospital, Tampa, and medical director at Gulf Coast Dermatology, Hudson, Fla.

The original 2.8-by-2.9-cm defect was closed with nylon skin sutures at the concentric redundant skin folds, and the final 0.7-by-0.5-cm defect left to granulate. "The skin here is bunchy, but in this type of patient you can get away with that because the skin is so loose. The puffiness will go down," he said.

Two months later, there was a small amount of breakdown and granulation tissue in the center of the defect, which was debrided in standard fashion with curetting, electrocautery, and topical aluminum chloride. Once the crust was scraped off the dermis was perfect, Dr. Hamill said at the meeting.

Because of the patient's complex medical problems she was unable to return for further follow-up, but a phone call to the nursing home determined that she was "perfectly healed and perfectly happy," he said.

"This is the type of surgery I would want my own grandmother to have because of its simplicity and lack of complications," he said.

The main disadvantages of the purse-string closure are the marked distortion of the skin immediately following the surgery and the possibility that simple scar revision may be needed in areas of high tension. But with a careful preoperative discussion, and the patient's being shown photos of other patients' outcomes, these are generally not major problems.

"In general, my patients have been extremely happy with this technique," Dr. Hamill concluded.

The lower left arm of the elderly nursing home patient with malignant melanoma in situ is shown before excision (left); immediately following excision (middle); and 2 weeks after surgery (right). The patient was "perfectly healed" and happy. Photos courtesy Dr. John Robert Hamill Jr.

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Targeted Therapy Slows Recurrent SCC in Patient

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PALM BEACH, FLA. — Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.

The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.

"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.

"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.

The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.

"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.

The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.

After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.

"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."

The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.

Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.

The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.

"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.

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PALM BEACH, FLA. — Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.

The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.

"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.

"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.

The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.

"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.

The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.

After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.

"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."

The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.

Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.

The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.

"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.

PALM BEACH, FLA. — Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.

The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.

"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.

"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.

The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.

"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.

The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.

After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.

"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."

The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.

Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.

The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.

"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.

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Joint Distraction Eases OA Knee Pain, Enables Cartilage Repair

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Joint distraction, a surgical technique that involves the placement of an external fixation frame around a degenerated joint, may offer a means of postponing the need for total knee replacement in young patients with severe osteoarthritis.

The cartilage in end-stage osteoarthritis (OA) is severely damaged, with fissuring; altered chondrocyte distribution and death; and a significant loss of extracellular matrix constituents. These changes in cartilage are accompanied by characteristic changes in periarticular bone and soft tissue. All these structural changes mean severe pain and functional limitations for patients, who typically rate their pain with a score of 80% out of a maximum of 100%, according to Dr. Floris P.J.G. Lafeber, of the University Medical Center Utrecht (the Netherlands).

The standard treatment for these patients is total knee replacement, which poses a dilemma for relatively young patients. “Total knee prostheses don't last forever,” Dr. Lafeber said. “They last on average 15 years, so if you have one placed at age 60 you are likely to need a replacement at 75, which is complicated and expensive, and the results are often disappointing. And then if you need another at age 90, the difficulties are really serious,” he said.

The rationale for joint distraction lies in the hypothesis that osteoarthritic cartilage is capable of self-repair if the joint is unloaded and chondrocyte nutrition is maintained. Pins are drilled through the soft tissue and bone just above and below the joint, and when the frame is in place the distance between the cartilaginous surfaces of the joint is increased by 5 mm. This transfers the load and stresses on cartilage away from the joint, eliminating further wear and tear.

Easing the mechanical stress is only one therapeutic aspect of the process of joint distraction. Springs within the distraction frame cause changes to occur in fluid pressure in the joint, with increases during loading and normalization with unloading. This continuous change in fluid pressure is important for the cartilage, because chondrocytes depend on synovial flow for nutrition, Dr. Lafeber explained.

The loading onto the frame also results in periarticular osteopenia, which in turn permits the sclerotic, osteoarthritic bone to become more flexible and the mineral content to normalize once the frame is removed. Furthermore, the periarticular bone turnover results in the release of multiple growth factors that can help repair the cartilage.

In collaboration with his center's orthopedic department, Dr. Lafeber and his colleagues in the department of rheumatology and clinical immunology began exploring this technique in a proof-of-concept study with ankle distraction. Although ankle OA is much less common than knee OA, in the case of failure an arthrodesis could be performed without much risk, he said.

A total of 73 patients underwent ankle distraction for 3 months, with the result that pain scores—rated at an average of 75% of a maximum of 100%—fell to 20%, while scores for function and clinical condition rose from approximately 25% at baseline to 80%. Some of these patients now have been followed for as long as 10 years, with continuing benefits.

The researchers next did a feasibility study that included three patients with knee OA, and found similar results on pain and function scores as well as on stiffness scores. They then undertook a larger prospective study in which 19 patients with severe knee OA (mean age, 48 years) have been treated with 2-month periods of distraction. Thus far, six have been followed for up to 2 years. Functional ability and clinical condition, poor at the onset with scores of 39% and 32%, respectively, increased to 82% and 81%.

Serum and urinary biomarkers of cartilage turnover were measured throughout a 12-month follow-up period. During the distraction phase there was an enormous turnover, with elevations of markers of both synthesis and breakdown, but after the distraction phase there was a gradual decrease of breakdown markers and a gradual increase in the markers of synthesis, indicating repair of the cartilage, Dr. Lafeber said.

Imaging studies also demonstrated improvements. In seven patients who have been followed for more than 12 months, joint space width shown on x-rays increased from slightly greater than 2.5 mm to more than 3.5 mm. “And on MRI studies done after 1 year and read in a blinded fashion in collaboration with Prof. Felix Eckstein, who is one of the leading researchers in this field, the amount of subchondral bone covered with cartilage was shown to have increased by 40%, cartilage volume increased by 50%, and cartilage thickness over the bone increased by 5%,” Dr. Lafeber said.

 

 

A patient's knee is shown before treatment (left). At 2 years after joint distraction treatment, the repaired cartilage allows for greater space within the joint.

An external fixation frame is shown here around the degenerative joint. Photos courtesy Dr. Floris P.J.G. Lafeber

The Iowa Ankle Experience Compares

Ankle distraction also has been performed and is being evaluated in a randomized study led by Dr. Annunziato Amendola of the University of Iowa, Iowa City.

“We are interested in posttraumatic osteoarthritis of joints, and the ankle in particular,” said Dr. Amendola, professor in the department of orthopedics and rehabilitation.

The study, which was funded by the National Institutes of Health, prospectively enrolled about 40 patients with posttraumatic ankle OA. They used the same ankle distraction technique as did Dr. Lafeber's group, but patients were randomized to distraction alone or to distraction plus continuous passive joint motion.

“There's lots of evidence indicating that motion is beneficial to a healing joint,” he said. During the course of the study, patients were evaluated clinically and radiographically, and with a special three-dimensional CT scanning technique to look at cartilage regeneration.

All but three patients have now undergone 2- and 3-year evaluations, and the results thus far have been comparable to the results they have had in Utrecht in terms of relief of pain, according to Dr. Amendola. Additional improvements have been seen over time, and patients in the motion group did significantly better at every time point than did the nonmotion group.

“I think this is quite an intriguing technique, and I'm sure you will be hearing more about it in the next few years,” Dr. Amendola said.

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Joint distraction, a surgical technique that involves the placement of an external fixation frame around a degenerated joint, may offer a means of postponing the need for total knee replacement in young patients with severe osteoarthritis.

The cartilage in end-stage osteoarthritis (OA) is severely damaged, with fissuring; altered chondrocyte distribution and death; and a significant loss of extracellular matrix constituents. These changes in cartilage are accompanied by characteristic changes in periarticular bone and soft tissue. All these structural changes mean severe pain and functional limitations for patients, who typically rate their pain with a score of 80% out of a maximum of 100%, according to Dr. Floris P.J.G. Lafeber, of the University Medical Center Utrecht (the Netherlands).

The standard treatment for these patients is total knee replacement, which poses a dilemma for relatively young patients. “Total knee prostheses don't last forever,” Dr. Lafeber said. “They last on average 15 years, so if you have one placed at age 60 you are likely to need a replacement at 75, which is complicated and expensive, and the results are often disappointing. And then if you need another at age 90, the difficulties are really serious,” he said.

The rationale for joint distraction lies in the hypothesis that osteoarthritic cartilage is capable of self-repair if the joint is unloaded and chondrocyte nutrition is maintained. Pins are drilled through the soft tissue and bone just above and below the joint, and when the frame is in place the distance between the cartilaginous surfaces of the joint is increased by 5 mm. This transfers the load and stresses on cartilage away from the joint, eliminating further wear and tear.

Easing the mechanical stress is only one therapeutic aspect of the process of joint distraction. Springs within the distraction frame cause changes to occur in fluid pressure in the joint, with increases during loading and normalization with unloading. This continuous change in fluid pressure is important for the cartilage, because chondrocytes depend on synovial flow for nutrition, Dr. Lafeber explained.

The loading onto the frame also results in periarticular osteopenia, which in turn permits the sclerotic, osteoarthritic bone to become more flexible and the mineral content to normalize once the frame is removed. Furthermore, the periarticular bone turnover results in the release of multiple growth factors that can help repair the cartilage.

In collaboration with his center's orthopedic department, Dr. Lafeber and his colleagues in the department of rheumatology and clinical immunology began exploring this technique in a proof-of-concept study with ankle distraction. Although ankle OA is much less common than knee OA, in the case of failure an arthrodesis could be performed without much risk, he said.

A total of 73 patients underwent ankle distraction for 3 months, with the result that pain scores—rated at an average of 75% of a maximum of 100%—fell to 20%, while scores for function and clinical condition rose from approximately 25% at baseline to 80%. Some of these patients now have been followed for as long as 10 years, with continuing benefits.

The researchers next did a feasibility study that included three patients with knee OA, and found similar results on pain and function scores as well as on stiffness scores. They then undertook a larger prospective study in which 19 patients with severe knee OA (mean age, 48 years) have been treated with 2-month periods of distraction. Thus far, six have been followed for up to 2 years. Functional ability and clinical condition, poor at the onset with scores of 39% and 32%, respectively, increased to 82% and 81%.

Serum and urinary biomarkers of cartilage turnover were measured throughout a 12-month follow-up period. During the distraction phase there was an enormous turnover, with elevations of markers of both synthesis and breakdown, but after the distraction phase there was a gradual decrease of breakdown markers and a gradual increase in the markers of synthesis, indicating repair of the cartilage, Dr. Lafeber said.

Imaging studies also demonstrated improvements. In seven patients who have been followed for more than 12 months, joint space width shown on x-rays increased from slightly greater than 2.5 mm to more than 3.5 mm. “And on MRI studies done after 1 year and read in a blinded fashion in collaboration with Prof. Felix Eckstein, who is one of the leading researchers in this field, the amount of subchondral bone covered with cartilage was shown to have increased by 40%, cartilage volume increased by 50%, and cartilage thickness over the bone increased by 5%,” Dr. Lafeber said.

 

 

A patient's knee is shown before treatment (left). At 2 years after joint distraction treatment, the repaired cartilage allows for greater space within the joint.

An external fixation frame is shown here around the degenerative joint. Photos courtesy Dr. Floris P.J.G. Lafeber

The Iowa Ankle Experience Compares

Ankle distraction also has been performed and is being evaluated in a randomized study led by Dr. Annunziato Amendola of the University of Iowa, Iowa City.

“We are interested in posttraumatic osteoarthritis of joints, and the ankle in particular,” said Dr. Amendola, professor in the department of orthopedics and rehabilitation.

The study, which was funded by the National Institutes of Health, prospectively enrolled about 40 patients with posttraumatic ankle OA. They used the same ankle distraction technique as did Dr. Lafeber's group, but patients were randomized to distraction alone or to distraction plus continuous passive joint motion.

“There's lots of evidence indicating that motion is beneficial to a healing joint,” he said. During the course of the study, patients were evaluated clinically and radiographically, and with a special three-dimensional CT scanning technique to look at cartilage regeneration.

All but three patients have now undergone 2- and 3-year evaluations, and the results thus far have been comparable to the results they have had in Utrecht in terms of relief of pain, according to Dr. Amendola. Additional improvements have been seen over time, and patients in the motion group did significantly better at every time point than did the nonmotion group.

“I think this is quite an intriguing technique, and I'm sure you will be hearing more about it in the next few years,” Dr. Amendola said.

Joint distraction, a surgical technique that involves the placement of an external fixation frame around a degenerated joint, may offer a means of postponing the need for total knee replacement in young patients with severe osteoarthritis.

The cartilage in end-stage osteoarthritis (OA) is severely damaged, with fissuring; altered chondrocyte distribution and death; and a significant loss of extracellular matrix constituents. These changes in cartilage are accompanied by characteristic changes in periarticular bone and soft tissue. All these structural changes mean severe pain and functional limitations for patients, who typically rate their pain with a score of 80% out of a maximum of 100%, according to Dr. Floris P.J.G. Lafeber, of the University Medical Center Utrecht (the Netherlands).

The standard treatment for these patients is total knee replacement, which poses a dilemma for relatively young patients. “Total knee prostheses don't last forever,” Dr. Lafeber said. “They last on average 15 years, so if you have one placed at age 60 you are likely to need a replacement at 75, which is complicated and expensive, and the results are often disappointing. And then if you need another at age 90, the difficulties are really serious,” he said.

The rationale for joint distraction lies in the hypothesis that osteoarthritic cartilage is capable of self-repair if the joint is unloaded and chondrocyte nutrition is maintained. Pins are drilled through the soft tissue and bone just above and below the joint, and when the frame is in place the distance between the cartilaginous surfaces of the joint is increased by 5 mm. This transfers the load and stresses on cartilage away from the joint, eliminating further wear and tear.

Easing the mechanical stress is only one therapeutic aspect of the process of joint distraction. Springs within the distraction frame cause changes to occur in fluid pressure in the joint, with increases during loading and normalization with unloading. This continuous change in fluid pressure is important for the cartilage, because chondrocytes depend on synovial flow for nutrition, Dr. Lafeber explained.

The loading onto the frame also results in periarticular osteopenia, which in turn permits the sclerotic, osteoarthritic bone to become more flexible and the mineral content to normalize once the frame is removed. Furthermore, the periarticular bone turnover results in the release of multiple growth factors that can help repair the cartilage.

In collaboration with his center's orthopedic department, Dr. Lafeber and his colleagues in the department of rheumatology and clinical immunology began exploring this technique in a proof-of-concept study with ankle distraction. Although ankle OA is much less common than knee OA, in the case of failure an arthrodesis could be performed without much risk, he said.

A total of 73 patients underwent ankle distraction for 3 months, with the result that pain scores—rated at an average of 75% of a maximum of 100%—fell to 20%, while scores for function and clinical condition rose from approximately 25% at baseline to 80%. Some of these patients now have been followed for as long as 10 years, with continuing benefits.

The researchers next did a feasibility study that included three patients with knee OA, and found similar results on pain and function scores as well as on stiffness scores. They then undertook a larger prospective study in which 19 patients with severe knee OA (mean age, 48 years) have been treated with 2-month periods of distraction. Thus far, six have been followed for up to 2 years. Functional ability and clinical condition, poor at the onset with scores of 39% and 32%, respectively, increased to 82% and 81%.

Serum and urinary biomarkers of cartilage turnover were measured throughout a 12-month follow-up period. During the distraction phase there was an enormous turnover, with elevations of markers of both synthesis and breakdown, but after the distraction phase there was a gradual decrease of breakdown markers and a gradual increase in the markers of synthesis, indicating repair of the cartilage, Dr. Lafeber said.

Imaging studies also demonstrated improvements. In seven patients who have been followed for more than 12 months, joint space width shown on x-rays increased from slightly greater than 2.5 mm to more than 3.5 mm. “And on MRI studies done after 1 year and read in a blinded fashion in collaboration with Prof. Felix Eckstein, who is one of the leading researchers in this field, the amount of subchondral bone covered with cartilage was shown to have increased by 40%, cartilage volume increased by 50%, and cartilage thickness over the bone increased by 5%,” Dr. Lafeber said.

 

 

A patient's knee is shown before treatment (left). At 2 years after joint distraction treatment, the repaired cartilage allows for greater space within the joint.

An external fixation frame is shown here around the degenerative joint. Photos courtesy Dr. Floris P.J.G. Lafeber

The Iowa Ankle Experience Compares

Ankle distraction also has been performed and is being evaluated in a randomized study led by Dr. Annunziato Amendola of the University of Iowa, Iowa City.

“We are interested in posttraumatic osteoarthritis of joints, and the ankle in particular,” said Dr. Amendola, professor in the department of orthopedics and rehabilitation.

The study, which was funded by the National Institutes of Health, prospectively enrolled about 40 patients with posttraumatic ankle OA. They used the same ankle distraction technique as did Dr. Lafeber's group, but patients were randomized to distraction alone or to distraction plus continuous passive joint motion.

“There's lots of evidence indicating that motion is beneficial to a healing joint,” he said. During the course of the study, patients were evaluated clinically and radiographically, and with a special three-dimensional CT scanning technique to look at cartilage regeneration.

All but three patients have now undergone 2- and 3-year evaluations, and the results thus far have been comparable to the results they have had in Utrecht in terms of relief of pain, according to Dr. Amendola. Additional improvements have been seen over time, and patients in the motion group did significantly better at every time point than did the nonmotion group.

“I think this is quite an intriguing technique, and I'm sure you will be hearing more about it in the next few years,” Dr. Amendola said.

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Low-Dose Steroids and Slow Taper Safe in PMR

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Low-Dose Steroids and Slow Taper Safe in PMR

NEW YORK — Prednisone starting at 10 mg per day with a slow taper over 17 months was effective in controlling polymyalgia rheumatica in 93% of 189 elderly patients treated, based on a case series presented at the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica.

The regimen was associated with lower total steroid doses, fewer adverse events, and similar or fewer relapses and recurrences than have been seen in other series of patients given higher steroid doses.

The initial prednisone dose recommended for polymyalgia rheumatica (PMR) is 10–20 mg/day. In reality, the doses used generally are closer to 20 mg/day than to 10 mg/day, due to concerns about the risk of treatment failure, said Dr. Luis J. Catoggio, head of rheumatology at the Hospital Italiano de Buenos Aires. However, his analyses suggest that rapid tapering of the steroid, not a low initial dose, is associated with poor outcomes in PMR.

Dr. Catoggio reported on 209 patients (164 women) with PMR seen between 1983 and 2002 and treated with 10 mg of prednisone in single morning dose. The patients' mean age was 71 years. Median disease duration at diagnosis was 2 months. Median erythrocyte sedimentation rate (ESR) at baseline was 56 mm/hr.

The shoulder girdle and pelvic girdle were affected in 96% and 87%, respectively. The neck and torso were affected in 62%, and synovitis was present in 24%.

Prednisone was initiated at 10 mg/day or less in 189 patients (90%), 12.5–15 mg/day in 16 patients (8%), and over 15 mg/day in 7 patients (3%). Dr. Catoggio explained that patients given doses above 10 mg/day were initially treated at other centers. Median time to clinical response was 10 days. Median time to ESR of less than 30 mm/hr was 60 days.

Five of the 15 patients with initial treatment failures had started on prednisone doses of 7.5 mg/day and subsequently responded to 10 mg/day.

The other 10 had started on 10 mg/day and later responded to 15 mg/day. Three patients (1.4%) relapsed within 3 months of initiating therapy and 74 (35%) relapsed later. Median time to relapse was 15 months, and mean steroid dose at relapse was 4.3 mg/day.

By the data cutoff date, 95 patients (45%) had been able to discontinue treatment. Recurrences were seen in 22, with a median time to recurrence of 7 months, but 11 ultimately were able to discontinue their steroids. In patients who finally discontinued prednisone, median duration of treatment was 19 months.

The schedule that employs a 20 mg/day starting dosage sustains that dosage for 1 month. The dose is then tapered by 2.5 mg every 2 weeks unless symptoms recur. (For the 17-month schedule used at Dr. Catoggio's hospital, see chart.)

The 20 mg/day schedule represents a minimum treatment period of 4.5 months and a total steroid dose of 1,650 mg. It was initially successful in only 4 of 27 patients (15%) in one study. The remaining patients all required upward adjustment of their steroids or longer duration of therapy (Ann. Intern. Med. 1999;159:577–84).

Compared with another study where the mean cumulative dose was 8,400 mg, the mean total dose of prednisone in Dr. Catoggio's cohort was 2,900 mg.

Adverse events were seen in 49 patients (23%). These included vertebral fractures in 11, hip and other fractures in 4, cataracts in 7, and hyperglycemia in 5.

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NEW YORK — Prednisone starting at 10 mg per day with a slow taper over 17 months was effective in controlling polymyalgia rheumatica in 93% of 189 elderly patients treated, based on a case series presented at the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica.

The regimen was associated with lower total steroid doses, fewer adverse events, and similar or fewer relapses and recurrences than have been seen in other series of patients given higher steroid doses.

The initial prednisone dose recommended for polymyalgia rheumatica (PMR) is 10–20 mg/day. In reality, the doses used generally are closer to 20 mg/day than to 10 mg/day, due to concerns about the risk of treatment failure, said Dr. Luis J. Catoggio, head of rheumatology at the Hospital Italiano de Buenos Aires. However, his analyses suggest that rapid tapering of the steroid, not a low initial dose, is associated with poor outcomes in PMR.

Dr. Catoggio reported on 209 patients (164 women) with PMR seen between 1983 and 2002 and treated with 10 mg of prednisone in single morning dose. The patients' mean age was 71 years. Median disease duration at diagnosis was 2 months. Median erythrocyte sedimentation rate (ESR) at baseline was 56 mm/hr.

The shoulder girdle and pelvic girdle were affected in 96% and 87%, respectively. The neck and torso were affected in 62%, and synovitis was present in 24%.

Prednisone was initiated at 10 mg/day or less in 189 patients (90%), 12.5–15 mg/day in 16 patients (8%), and over 15 mg/day in 7 patients (3%). Dr. Catoggio explained that patients given doses above 10 mg/day were initially treated at other centers. Median time to clinical response was 10 days. Median time to ESR of less than 30 mm/hr was 60 days.

Five of the 15 patients with initial treatment failures had started on prednisone doses of 7.5 mg/day and subsequently responded to 10 mg/day.

The other 10 had started on 10 mg/day and later responded to 15 mg/day. Three patients (1.4%) relapsed within 3 months of initiating therapy and 74 (35%) relapsed later. Median time to relapse was 15 months, and mean steroid dose at relapse was 4.3 mg/day.

By the data cutoff date, 95 patients (45%) had been able to discontinue treatment. Recurrences were seen in 22, with a median time to recurrence of 7 months, but 11 ultimately were able to discontinue their steroids. In patients who finally discontinued prednisone, median duration of treatment was 19 months.

The schedule that employs a 20 mg/day starting dosage sustains that dosage for 1 month. The dose is then tapered by 2.5 mg every 2 weeks unless symptoms recur. (For the 17-month schedule used at Dr. Catoggio's hospital, see chart.)

The 20 mg/day schedule represents a minimum treatment period of 4.5 months and a total steroid dose of 1,650 mg. It was initially successful in only 4 of 27 patients (15%) in one study. The remaining patients all required upward adjustment of their steroids or longer duration of therapy (Ann. Intern. Med. 1999;159:577–84).

Compared with another study where the mean cumulative dose was 8,400 mg, the mean total dose of prednisone in Dr. Catoggio's cohort was 2,900 mg.

Adverse events were seen in 49 patients (23%). These included vertebral fractures in 11, hip and other fractures in 4, cataracts in 7, and hyperglycemia in 5.

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK — Prednisone starting at 10 mg per day with a slow taper over 17 months was effective in controlling polymyalgia rheumatica in 93% of 189 elderly patients treated, based on a case series presented at the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica.

The regimen was associated with lower total steroid doses, fewer adverse events, and similar or fewer relapses and recurrences than have been seen in other series of patients given higher steroid doses.

The initial prednisone dose recommended for polymyalgia rheumatica (PMR) is 10–20 mg/day. In reality, the doses used generally are closer to 20 mg/day than to 10 mg/day, due to concerns about the risk of treatment failure, said Dr. Luis J. Catoggio, head of rheumatology at the Hospital Italiano de Buenos Aires. However, his analyses suggest that rapid tapering of the steroid, not a low initial dose, is associated with poor outcomes in PMR.

Dr. Catoggio reported on 209 patients (164 women) with PMR seen between 1983 and 2002 and treated with 10 mg of prednisone in single morning dose. The patients' mean age was 71 years. Median disease duration at diagnosis was 2 months. Median erythrocyte sedimentation rate (ESR) at baseline was 56 mm/hr.

The shoulder girdle and pelvic girdle were affected in 96% and 87%, respectively. The neck and torso were affected in 62%, and synovitis was present in 24%.

Prednisone was initiated at 10 mg/day or less in 189 patients (90%), 12.5–15 mg/day in 16 patients (8%), and over 15 mg/day in 7 patients (3%). Dr. Catoggio explained that patients given doses above 10 mg/day were initially treated at other centers. Median time to clinical response was 10 days. Median time to ESR of less than 30 mm/hr was 60 days.

Five of the 15 patients with initial treatment failures had started on prednisone doses of 7.5 mg/day and subsequently responded to 10 mg/day.

The other 10 had started on 10 mg/day and later responded to 15 mg/day. Three patients (1.4%) relapsed within 3 months of initiating therapy and 74 (35%) relapsed later. Median time to relapse was 15 months, and mean steroid dose at relapse was 4.3 mg/day.

By the data cutoff date, 95 patients (45%) had been able to discontinue treatment. Recurrences were seen in 22, with a median time to recurrence of 7 months, but 11 ultimately were able to discontinue their steroids. In patients who finally discontinued prednisone, median duration of treatment was 19 months.

The schedule that employs a 20 mg/day starting dosage sustains that dosage for 1 month. The dose is then tapered by 2.5 mg every 2 weeks unless symptoms recur. (For the 17-month schedule used at Dr. Catoggio's hospital, see chart.)

The 20 mg/day schedule represents a minimum treatment period of 4.5 months and a total steroid dose of 1,650 mg. It was initially successful in only 4 of 27 patients (15%) in one study. The remaining patients all required upward adjustment of their steroids or longer duration of therapy (Ann. Intern. Med. 1999;159:577–84).

Compared with another study where the mean cumulative dose was 8,400 mg, the mean total dose of prednisone in Dr. Catoggio's cohort was 2,900 mg.

Adverse events were seen in 49 patients (23%). These included vertebral fractures in 11, hip and other fractures in 4, cataracts in 7, and hyperglycemia in 5.

ELSEVIER GLOBAL MEDICAL NEWS

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