Increased risk of bladder cancer in New England may be partly due to drinking water from private wells, particularly dug wells established during the first half of the 20th century, according to researchers from the National Cancer Institute. Bladder cancer mortality rates have been elevated in northern New England for at least 5 decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than in the United States overall, researchers said in a press release.

To explore reasons for the elevated risk, NCI investigators and colleagues in New England compared well water consumption, smoking, occupation, ancestry, use of wood-burning stoves, and consumption of various foods for 1,213 people in New England who were newly diagnosed with bladder cancer, and 1,418 people without bladder cancer who were matched by geographic area.

©Sebastian Kaulitzki/thinkstock

The amount of arsenic ingested through drinking water was estimated based on current levels and historical information. Increasing cumulative exposure was associated with an increasing risk of bladder cancer. Among people who used private wells, people who drank the most water had twice the risk of those who drank the least. Highest risk was seen among those who drank water from dug wells established before 1960, when the use of arsenic-based pesticides was common.

“Arsenic is an established cause of bladder cancer, largely based on observations from earlier studies in highly exposed populations,” said Debra Silverman, Sc.D., chief of the Occupational and Environmental Epidemiology Branch of the NCI, Rockville, Md., and senior author on the study. “However, emerging evidence suggests that low to moderate levels of exposure may also increase risk,” she said in the press release.

“Although smoking and employment in high-risk occupations both showed their expected associations with bladder cancer risk in this population, they were similar to those found in other populations,” Dr. Silverman said. “This suggests that neither risk factor explains the excess occurrence of bladder cancer in northern New England.”

These study results indicate historical consumption of water from private wells, particularly dug wells in an era when arsenic-based pesticides were widely used, may have contributed to the excess rate in New England residents, Dr. Silverman and colleagues concluded.

The study was published in the Journal of the National Cancer Institute (2016;108[9]:djw099).

[email protected]

On Twitter @NikolaidesLaura

Increased risk of bladder cancer in New England may be partly due to drinking water from private wells, particularly dug wells established during the first half of the 20th century, according to researchers from the National Cancer Institute. Bladder cancer mortality rates have been elevated in northern New England for at least 5 decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than in the United States overall, researchers said in a press release.

To explore reasons for the elevated risk, NCI investigators and colleagues in New England compared well water consumption, smoking, occupation, ancestry, use of wood-burning stoves, and consumption of various foods for 1,213 people in New England who were newly diagnosed with bladder cancer, and 1,418 people without bladder cancer who were matched by geographic area.

©Sebastian Kaulitzki/thinkstock

The amount of arsenic ingested through drinking water was estimated based on current levels and historical information. Increasing cumulative exposure was associated with an increasing risk of bladder cancer. Among people who used private wells, people who drank the most water had twice the risk of those who drank the least. Highest risk was seen among those who drank water from dug wells established before 1960, when the use of arsenic-based pesticides was common.

“Arsenic is an established cause of bladder cancer, largely based on observations from earlier studies in highly exposed populations,” said Debra Silverman, Sc.D., chief of the Occupational and Environmental Epidemiology Branch of the NCI, Rockville, Md., and senior author on the study. “However, emerging evidence suggests that low to moderate levels of exposure may also increase risk,” she said in the press release.

“Although smoking and employment in high-risk occupations both showed their expected associations with bladder cancer risk in this population, they were similar to those found in other populations,” Dr. Silverman said. “This suggests that neither risk factor explains the excess occurrence of bladder cancer in northern New England.”

These study results indicate historical consumption of water from private wells, particularly dug wells in an era when arsenic-based pesticides were widely used, may have contributed to the excess rate in New England residents, Dr. Silverman and colleagues concluded.

The study was published in the Journal of the National Cancer Institute (2016;108[9]:djw099).

[email protected]

On Twitter @NikolaidesLaura

Increased risk of bladder cancer in New England may be partly due to drinking water from private wells, particularly dug wells established during the first half of the 20th century, according to researchers from the National Cancer Institute. Bladder cancer mortality rates have been elevated in northern New England for at least 5 decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than in the United States overall, researchers said in a press release.

To explore reasons for the elevated risk, NCI investigators and colleagues in New England compared well water consumption, smoking, occupation, ancestry, use of wood-burning stoves, and consumption of various foods for 1,213 people in New England who were newly diagnosed with bladder cancer, and 1,418 people without bladder cancer who were matched by geographic area.

©Sebastian Kaulitzki/thinkstock

The amount of arsenic ingested through drinking water was estimated based on current levels and historical information. Increasing cumulative exposure was associated with an increasing risk of bladder cancer. Among people who used private wells, people who drank the most water had twice the risk of those who drank the least. Highest risk was seen among those who drank water from dug wells established before 1960, when the use of arsenic-based pesticides was common.

“Arsenic is an established cause of bladder cancer, largely based on observations from earlier studies in highly exposed populations,” said Debra Silverman, Sc.D., chief of the Occupational and Environmental Epidemiology Branch of the NCI, Rockville, Md., and senior author on the study. “However, emerging evidence suggests that low to moderate levels of exposure may also increase risk,” she said in the press release.

“Although smoking and employment in high-risk occupations both showed their expected associations with bladder cancer risk in this population, they were similar to those found in other populations,” Dr. Silverman said. “This suggests that neither risk factor explains the excess occurrence of bladder cancer in northern New England.”

These study results indicate historical consumption of water from private wells, particularly dug wells in an era when arsenic-based pesticides were widely used, may have contributed to the excess rate in New England residents, Dr. Silverman and colleagues concluded.

The study was published in the Journal of the National Cancer Institute (2016;108[9]:djw099).

[email protected]

On Twitter @NikolaidesLaura

The investigational interleukin-17 inhibitor brodalumab was safe and effective in a small phase III Japanese study of adults with two rare and severe types of psoriasis, generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE). The results were published in the British Journal of Dermatology.

The 52-week open label studyevaluated the safety and efficacy of brodalumab in 30 Japanese adults (mean age 48 years) with GPP (12 patients) and PsE (18 patients). Brodalumab, a human monoclonal antibody against human IL-17RA that blocks the biologic activities of IL-17, was administered by subcutaneous injection. Efficacy was assessed via Clinical Global Impression of Improvement (CGI) scores, the primary endpoint (Br J Dermatol. 2016 April 23. doi: 10.1111/bjd.14702).

A high proportion of patients with either disease achieved “improved” or “remission” CGI scores at weeks 2, 12, and 52, reported Dr. Kenshi Yamasaki, of the department of dermatology at Tohoku University, Miyagi, Japan, and his associates

At week 52, almost 92% of those with GPP and 100% of those with PsE had achieved “improved” or “remission” scores. The most common adverse event was nasopharyngitis, which occurred in one-third of patients. Infection-related adverse events were grade 1 or 2, no adverse events were fatal, and none of the five serious adverse events noted were considered to be attributable to treatment, they added. Although anti-brodalumab neutralizing antibodies were not detected, one patient tested positive for anti-brodalumab binding antibodies.

Noting that treatment with brodalumab has been associated with significant improvements in patients with plaque psoriasis and psoriatic arthritis in phase II and III studies, “results from this study confirm that brodalumab can improve patient symptoms not long after treatment is initiated,” in patients with GPP and PsE, the authors concluded. While acknowledging the study limitations, including the open label design and a small sample size, they added, “IL-17RA blocking will be a promising therapeutic target in patients with GPP and PsE.”

The safety profile and low expression of anti-brodalumab antibodies indicated that brodalumab was suitable for long-term use, they said.

The study was funded by Kyowa Hakko Kirin. All authors disclosed ties to pharmaceutical companies, including the funding source; one author is an employee of the company.

The investigational interleukin-17 inhibitor brodalumab was safe and effective in a small phase III Japanese study of adults with two rare and severe types of psoriasis, generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE). The results were published in the British Journal of Dermatology.

The 52-week open label studyevaluated the safety and efficacy of brodalumab in 30 Japanese adults (mean age 48 years) with GPP (12 patients) and PsE (18 patients). Brodalumab, a human monoclonal antibody against human IL-17RA that blocks the biologic activities of IL-17, was administered by subcutaneous injection. Efficacy was assessed via Clinical Global Impression of Improvement (CGI) scores, the primary endpoint (Br J Dermatol. 2016 April 23. doi: 10.1111/bjd.14702).

A high proportion of patients with either disease achieved “improved” or “remission” CGI scores at weeks 2, 12, and 52, reported Dr. Kenshi Yamasaki, of the department of dermatology at Tohoku University, Miyagi, Japan, and his associates

At week 52, almost 92% of those with GPP and 100% of those with PsE had achieved “improved” or “remission” scores. The most common adverse event was nasopharyngitis, which occurred in one-third of patients. Infection-related adverse events were grade 1 or 2, no adverse events were fatal, and none of the five serious adverse events noted were considered to be attributable to treatment, they added. Although anti-brodalumab neutralizing antibodies were not detected, one patient tested positive for anti-brodalumab binding antibodies.

Noting that treatment with brodalumab has been associated with significant improvements in patients with plaque psoriasis and psoriatic arthritis in phase II and III studies, “results from this study confirm that brodalumab can improve patient symptoms not long after treatment is initiated,” in patients with GPP and PsE, the authors concluded. While acknowledging the study limitations, including the open label design and a small sample size, they added, “IL-17RA blocking will be a promising therapeutic target in patients with GPP and PsE.”

The safety profile and low expression of anti-brodalumab antibodies indicated that brodalumab was suitable for long-term use, they said.

The study was funded by Kyowa Hakko Kirin. All authors disclosed ties to pharmaceutical companies, including the funding source; one author is an employee of the company.

The investigational interleukin-17 inhibitor brodalumab was safe and effective in a small phase III Japanese study of adults with two rare and severe types of psoriasis, generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE). The results were published in the British Journal of Dermatology.

The 52-week open label studyevaluated the safety and efficacy of brodalumab in 30 Japanese adults (mean age 48 years) with GPP (12 patients) and PsE (18 patients). Brodalumab, a human monoclonal antibody against human IL-17RA that blocks the biologic activities of IL-17, was administered by subcutaneous injection. Efficacy was assessed via Clinical Global Impression of Improvement (CGI) scores, the primary endpoint (Br J Dermatol. 2016 April 23. doi: 10.1111/bjd.14702).

A high proportion of patients with either disease achieved “improved” or “remission” CGI scores at weeks 2, 12, and 52, reported Dr. Kenshi Yamasaki, of the department of dermatology at Tohoku University, Miyagi, Japan, and his associates

At week 52, almost 92% of those with GPP and 100% of those with PsE had achieved “improved” or “remission” scores. The most common adverse event was nasopharyngitis, which occurred in one-third of patients. Infection-related adverse events were grade 1 or 2, no adverse events were fatal, and none of the five serious adverse events noted were considered to be attributable to treatment, they added. Although anti-brodalumab neutralizing antibodies were not detected, one patient tested positive for anti-brodalumab binding antibodies.

Noting that treatment with brodalumab has been associated with significant improvements in patients with plaque psoriasis and psoriatic arthritis in phase II and III studies, “results from this study confirm that brodalumab can improve patient symptoms not long after treatment is initiated,” in patients with GPP and PsE, the authors concluded. While acknowledging the study limitations, including the open label design and a small sample size, they added, “IL-17RA blocking will be a promising therapeutic target in patients with GPP and PsE.”

The safety profile and low expression of anti-brodalumab antibodies indicated that brodalumab was suitable for long-term use, they said.

The study was funded by Kyowa Hakko Kirin. All authors disclosed ties to pharmaceutical companies, including the funding source; one author is an employee of the company.

CHICAGO – Using an inhaled long-acting beta agonist and corticosteroid to treat patients with moderate chronic obstructive pulmonary disease who have known cardiovascular disease had no impact on the cardiovascular event rate in the landmark SUMMIT trial, Dr. David E. Newby reported at the annual meeting of the American College of Cardiology.

SUMMIT (the Study to Understand Mortality and Morbidity) was a randomized, double-blind, placebo-controlled, 43-country, four-arm clinical trial in which 16,485 patients with moderate COPD were placed on once-daily inhaled fluticasone furoate/vilanterol 100/25 mcg by dry powder inhaler (Breo Ellipta), either drug alone, or placebo for an average of 2 years. Two-thirds of participants had overt cardiovascular disease; the rest were at high risk as defined by age greater than 60 years plus the presence of two or more cardiovascular risk factors.

This was the first large prospective clinical trial to investigate the impact of respiratory therapy on survival in patients with two commonly comorbid conditions. The incidence of major adverse cardiovascular events – a prespecified secondary endpoint – was of major interest because some other long-acting beta agonists have been linked to increased cardiovascular risk, explained Dr. Newby of the University of Edinburgh.

The primary endpoint in SUMMIT was all-cause mortality. The 12.2% relative risk reduction in the fluticasone furoate/vilanterol group, compared with placebo, didn’t achieve statistical significance. Neither did the 7.4% reduction in the secondary composite endpoint of cardiovascular death, MI, stroke, unstable angina, or TIA seen in the corticosteroid/LABA group, which is reassuring from a safety standpoint, he noted.

A positive result was seen for another secondary endpoint: the rate of lung function decline as measured by forced expiratory volume in 1 second. The rate of decline was 8 mL/year less with fluticasone furoate/vilanterol, compared with placebo.

The Breo Ellipta group also had significantly lower rates of moderate or severe COPD exacerbations, hospitalization for exacerbations, and improved quality of life as measured by the St. George’s Respiratory Questionnaire – COPD total score at 12 months.

The SUMMIT trial was sponsored by GlaxoSmithKline. The presenter is a consultant to GSK and eight other pharmaceutical companies.

[email protected]

CHICAGO – Using an inhaled long-acting beta agonist and corticosteroid to treat patients with moderate chronic obstructive pulmonary disease who have known cardiovascular disease had no impact on the cardiovascular event rate in the landmark SUMMIT trial, Dr. David E. Newby reported at the annual meeting of the American College of Cardiology.

SUMMIT (the Study to Understand Mortality and Morbidity) was a randomized, double-blind, placebo-controlled, 43-country, four-arm clinical trial in which 16,485 patients with moderate COPD were placed on once-daily inhaled fluticasone furoate/vilanterol 100/25 mcg by dry powder inhaler (Breo Ellipta), either drug alone, or placebo for an average of 2 years. Two-thirds of participants had overt cardiovascular disease; the rest were at high risk as defined by age greater than 60 years plus the presence of two or more cardiovascular risk factors.

This was the first large prospective clinical trial to investigate the impact of respiratory therapy on survival in patients with two commonly comorbid conditions. The incidence of major adverse cardiovascular events – a prespecified secondary endpoint – was of major interest because some other long-acting beta agonists have been linked to increased cardiovascular risk, explained Dr. Newby of the University of Edinburgh.

The primary endpoint in SUMMIT was all-cause mortality. The 12.2% relative risk reduction in the fluticasone furoate/vilanterol group, compared with placebo, didn’t achieve statistical significance. Neither did the 7.4% reduction in the secondary composite endpoint of cardiovascular death, MI, stroke, unstable angina, or TIA seen in the corticosteroid/LABA group, which is reassuring from a safety standpoint, he noted.

A positive result was seen for another secondary endpoint: the rate of lung function decline as measured by forced expiratory volume in 1 second. The rate of decline was 8 mL/year less with fluticasone furoate/vilanterol, compared with placebo.

The Breo Ellipta group also had significantly lower rates of moderate or severe COPD exacerbations, hospitalization for exacerbations, and improved quality of life as measured by the St. George’s Respiratory Questionnaire – COPD total score at 12 months.

The SUMMIT trial was sponsored by GlaxoSmithKline. The presenter is a consultant to GSK and eight other pharmaceutical companies.

[email protected]

CHICAGO – Using an inhaled long-acting beta agonist and corticosteroid to treat patients with moderate chronic obstructive pulmonary disease who have known cardiovascular disease had no impact on the cardiovascular event rate in the landmark SUMMIT trial, Dr. David E. Newby reported at the annual meeting of the American College of Cardiology.

SUMMIT (the Study to Understand Mortality and Morbidity) was a randomized, double-blind, placebo-controlled, 43-country, four-arm clinical trial in which 16,485 patients with moderate COPD were placed on once-daily inhaled fluticasone furoate/vilanterol 100/25 mcg by dry powder inhaler (Breo Ellipta), either drug alone, or placebo for an average of 2 years. Two-thirds of participants had overt cardiovascular disease; the rest were at high risk as defined by age greater than 60 years plus the presence of two or more cardiovascular risk factors.

This was the first large prospective clinical trial to investigate the impact of respiratory therapy on survival in patients with two commonly comorbid conditions. The incidence of major adverse cardiovascular events – a prespecified secondary endpoint – was of major interest because some other long-acting beta agonists have been linked to increased cardiovascular risk, explained Dr. Newby of the University of Edinburgh.

The primary endpoint in SUMMIT was all-cause mortality. The 12.2% relative risk reduction in the fluticasone furoate/vilanterol group, compared with placebo, didn’t achieve statistical significance. Neither did the 7.4% reduction in the secondary composite endpoint of cardiovascular death, MI, stroke, unstable angina, or TIA seen in the corticosteroid/LABA group, which is reassuring from a safety standpoint, he noted.

A positive result was seen for another secondary endpoint: the rate of lung function decline as measured by forced expiratory volume in 1 second. The rate of decline was 8 mL/year less with fluticasone furoate/vilanterol, compared with placebo.

The Breo Ellipta group also had significantly lower rates of moderate or severe COPD exacerbations, hospitalization for exacerbations, and improved quality of life as measured by the St. George’s Respiratory Questionnaire – COPD total score at 12 months.

The SUMMIT trial was sponsored by GlaxoSmithKline. The presenter is a consultant to GSK and eight other pharmaceutical companies.

[email protected]

One of the determinants of a successful surgical outcome is the perception, on the part of the patient, of the cosmesis of a scar. The use of Z-plasty is an accepted means by which to break a scar up into smaller geometric segments. In some instances, a Z-plasty is used for scar revision to elongate a scar that may be pulling. However, a study published online in JAMA Facial Plastic Surgery on April 7 mentions the lack of studies measuring the perception of these scars among the normal population after surgery.

Ratnarathorn et al designed a prospective Internet-based survey with a goal of 580 responses to give a power of 90%. The survey was distributed to a diverse sample of the US population. Using editing software, Ratnarathorn et al superimposed a mature linear scar and a mature zigzag scar onto the faces of standardized headshots from 4 individuals (2 males, 2 females). Each individual had 1 image of the linear scar and 1 image of the zigzag scars superimposed onto each of 3 anatomical areas—forehead (flat surface), cheek (convex surface), and temple (concave surface)—yielding 24 images for the respondents to assess.

A 24.5% (n=876) response rate was achieved with 3575 surveys distributed. Of the 876 respondents, 810 (92.5%) completed the survey (46.1% male, 53.9% female). Respondents were asked to rate the scars on a scale of 1 to 10 (1=normal skin; 10=worst scar imaginable).

Results were statistically significantly lower (better) for the linear scars compared to the zigzag scars in all 3 anatomic areas and across both male and female groups with a mean score of 2.9 versus 4.5 (P<.001). A multivariable regression model of respondent age, sex, educational level, and income showed no statistically significant effect on the rating of the scars.

What’s the issue?

This study highlights some interesting points. Coming from an academic practice, we oftentimes find ourselves teaching residents a variety of skin closure techniques to deal with defects from skin cancer excisions. It is both challenging and fun to design complex closures; however, we must keep in mind what is in the best interest of the patient. One of the points I try to emphasize is that we must understand that there are no true straight lines on the face. In fact, when scars from procedures appear as geometric shapes on the face, our eyes tend to be drawn to them. For this reason, it often is best to use curvilinear lines wherever possible. Ratnarathorn et al highlights that point exactly. More studies of this nature are needed to assess what is perceived as a successful outcome, by both physicians and patients.

As you follow your patients for the long-term, have you noticed that you perform more or fewer zigzag scars?

We want to know your views! Tell us what you think.

One of the determinants of a successful surgical outcome is the perception, on the part of the patient, of the cosmesis of a scar. The use of Z-plasty is an accepted means by which to break a scar up into smaller geometric segments. In some instances, a Z-plasty is used for scar revision to elongate a scar that may be pulling. However, a study published online in JAMA Facial Plastic Surgery on April 7 mentions the lack of studies measuring the perception of these scars among the normal population after surgery.

Ratnarathorn et al designed a prospective Internet-based survey with a goal of 580 responses to give a power of 90%. The survey was distributed to a diverse sample of the US population. Using editing software, Ratnarathorn et al superimposed a mature linear scar and a mature zigzag scar onto the faces of standardized headshots from 4 individuals (2 males, 2 females). Each individual had 1 image of the linear scar and 1 image of the zigzag scars superimposed onto each of 3 anatomical areas—forehead (flat surface), cheek (convex surface), and temple (concave surface)—yielding 24 images for the respondents to assess.

A 24.5% (n=876) response rate was achieved with 3575 surveys distributed. Of the 876 respondents, 810 (92.5%) completed the survey (46.1% male, 53.9% female). Respondents were asked to rate the scars on a scale of 1 to 10 (1=normal skin; 10=worst scar imaginable).

Results were statistically significantly lower (better) for the linear scars compared to the zigzag scars in all 3 anatomic areas and across both male and female groups with a mean score of 2.9 versus 4.5 (P<.001). A multivariable regression model of respondent age, sex, educational level, and income showed no statistically significant effect on the rating of the scars.

What’s the issue?

This study highlights some interesting points. Coming from an academic practice, we oftentimes find ourselves teaching residents a variety of skin closure techniques to deal with defects from skin cancer excisions. It is both challenging and fun to design complex closures; however, we must keep in mind what is in the best interest of the patient. One of the points I try to emphasize is that we must understand that there are no true straight lines on the face. In fact, when scars from procedures appear as geometric shapes on the face, our eyes tend to be drawn to them. For this reason, it often is best to use curvilinear lines wherever possible. Ratnarathorn et al highlights that point exactly. More studies of this nature are needed to assess what is perceived as a successful outcome, by both physicians and patients.

As you follow your patients for the long-term, have you noticed that you perform more or fewer zigzag scars?

We want to know your views! Tell us what you think.

One of the determinants of a successful surgical outcome is the perception, on the part of the patient, of the cosmesis of a scar. The use of Z-plasty is an accepted means by which to break a scar up into smaller geometric segments. In some instances, a Z-plasty is used for scar revision to elongate a scar that may be pulling. However, a study published online in JAMA Facial Plastic Surgery on April 7 mentions the lack of studies measuring the perception of these scars among the normal population after surgery.

Ratnarathorn et al designed a prospective Internet-based survey with a goal of 580 responses to give a power of 90%. The survey was distributed to a diverse sample of the US population. Using editing software, Ratnarathorn et al superimposed a mature linear scar and a mature zigzag scar onto the faces of standardized headshots from 4 individuals (2 males, 2 females). Each individual had 1 image of the linear scar and 1 image of the zigzag scars superimposed onto each of 3 anatomical areas—forehead (flat surface), cheek (convex surface), and temple (concave surface)—yielding 24 images for the respondents to assess.

A 24.5% (n=876) response rate was achieved with 3575 surveys distributed. Of the 876 respondents, 810 (92.5%) completed the survey (46.1% male, 53.9% female). Respondents were asked to rate the scars on a scale of 1 to 10 (1=normal skin; 10=worst scar imaginable).

Results were statistically significantly lower (better) for the linear scars compared to the zigzag scars in all 3 anatomic areas and across both male and female groups with a mean score of 2.9 versus 4.5 (P<.001). A multivariable regression model of respondent age, sex, educational level, and income showed no statistically significant effect on the rating of the scars.

What’s the issue?

This study highlights some interesting points. Coming from an academic practice, we oftentimes find ourselves teaching residents a variety of skin closure techniques to deal with defects from skin cancer excisions. It is both challenging and fun to design complex closures; however, we must keep in mind what is in the best interest of the patient. One of the points I try to emphasize is that we must understand that there are no true straight lines on the face. In fact, when scars from procedures appear as geometric shapes on the face, our eyes tend to be drawn to them. For this reason, it often is best to use curvilinear lines wherever possible. Ratnarathorn et al highlights that point exactly. More studies of this nature are needed to assess what is perceived as a successful outcome, by both physicians and patients.

As you follow your patients for the long-term, have you noticed that you perform more or fewer zigzag scars?

We want to know your views! Tell us what you think.

One of the great honors of my professional career was being nominated to the presidency of the Society of Gynecologic Surgeons and being given the opportunity to deliver the presidential address at the Society’s 42nd annual scientific meeting in Palm Springs, Calif.

One of the core principles of the SGS mission statement is supporting excellence in gynecologic surgery and, to that end, the main focus of my term was to address the decline in vaginal hysterectomy rates. What follows is an excerpt from my speech explaining the rationale for vaginal hysterectomy (VH) and steps the SGS is taking to reverse the decline.

Unfortunately, what is happening in today’s practice environment is declining use of vaginal hysterectomy, with concomitant increases in endoscopic hysterectomy, mostly with the use of robotic assistance. Being the president of a society previously known as the Vaginal Surgeons Society, it would not be surprising to hear that I have been accused of being “anti-robot.”

Nothing could be further from the truth.

When we talk about the surgical treatment of patients with endometrial and cervical cancer, I do not need a randomized clinical trial to know that not making a laparotomy incision is probably a good thing when you’re treating these patients. There are benefits to using robotic techniques in this subpopulation; it is cost effective due to the reduced morbidity and straight stick laparoscopy for these patients is difficult to perform; therefore it’s not been as widely published or performed. I believe that robotic hysterectomy for these disorders should be the standard of care. In this regard, I am pro robot (Gynecologic Oncol. 2015;138[2]:457-71).

On the other hand, I also don’t need a randomized trial (even though randomized trials exist) to know that if you have a choice to make, or not make, extra incisions during surgery, it’s better to not make the extra incisions.

It’s certainly not rocket science to know that a Zeppelin or Heaney clamp is orders of magnitude cheaper than equipment required to perform an endoscopic hysterectomy – $22.25 USD for instrument and $3.19 USD to process per case (Am J Obstet Gynecol. 2016;214[4]:S461-2]).

Level I evidence demonstrates that when compared to other minimally invasive hysterectomy techniques, vaginal hysterectomy is cheaper, the convalescence is stable or reduced, and the complication rates are lower (Cochrane Database Syst Rev. 2015 Aug. 12;8:CD003677).

Moreover, if you don’t place a port, you can’t get a port site complication (these complications are rare, but potentially serious when they occur). You can’t perforate the common iliac vein. You can’t put a Veress needle through the small bowel. You can’t get a Richter’s hernia. And finally, while you can get cuff dehiscence with vaginal hysterectomy, I’ve never seen it, and this is a real issue with the endoscopic approaches (Cochrane Database Syst Rev. 2012 Feb. 15;2:CD006583 ).

This isn’t just my opinion. Every major surgical society has recommended vaginal hysterectomy when technically feasible.

Of course, “technical feasibility” is the kicker and it’s important to ask what this means.

First, we have to look at what I call the hysterectomy continuum. There are the young, sexually-active women with uterovaginal procidentia where an endoscopic approach for sacral colpopexy might be considered. Then you have patients who are vaginally parous, have a mobile uterus less than 12 weeks in size, and have a basic gynecologic condition such as dysfunctional uterine bleeding, cervical intraepithelial neoplasia, or painful menses (this is about 40%-50% of patients when I reviewed internal North Valley Permanente Group data in 2012); these patients are certainly excellent candidates for vaginal hysterectomy. Then there are patients with 30-week-size fibroid uterus, three prior C-sections, and known stage 4 endometriosis (where an open or robotic approach would be justified).

Second, we have to address the contradictory data presented in the literature regarding vaginal hysterectomy rates. On one hand, we have data from large case series and randomized, controlled trials which demonstrate that it’s feasible to perform a high percentage of vaginal hysterectomies (Obstet Gynecol. 2004;103[6]:1321-5and Arch Gynecol Obstet. 2014;290[3]:485-91). On the other hand, 40 years of population data show the opposite (Obstet Gynecol. 2009;114[5]:1041-8).

In the pre-endoscopic era, 80% and 20% of hysterectomies were performed via the abdominal and vaginal routes, respectively. During the laparoscopic era, 64%, 22%, and 14% of hysterectomies were performed via the abdominal, vaginal, and laparoscopic routes, respectively. And during the current robotic era, it is now 32%, 16%, 28%, and 25% performed via the abdominal, vaginal, laparoscopic, and robotic routes, respectively.

During this 40-year time frame, despite data and recommendations that support vaginal hysterectomy, there has never been an obvious incentive to perform this procedure (e.g. to my knowledge, no one has ever been paid more to do a vaginal hysterectomy, or been prominently featured on a hospital’s website regarding his or her ability to perform an “incision-less” hysterectomy (Am J Obstet Gynecol. 2012;207[3]:174.e1-174.e7). Why weren’t and why aren’t we outraged about this? I have always been under the impression that cheaper and safer is better!

The first thing I hear to explain this – mostly from robotic surgeons and from the robotic surgery device sales representatives – is that the decline in the proportion of vaginal hysterectomies is irrelevant in that it has taken the robot to meaningfully reduce open hysterectomy rates. The other argument I hear – mostly from the laparoscopic surgeons – is that vaginal hysterectomy rates have not changed because most gynecologists cannot and will never be able to perform the procedure. So, what is the point of even discussing solutions?

I disagree with the laparoscopic and robotic surgeons. We should be outraged and do something to effect change. Vaginal hysterectomy offers better value (for surgeons who aren’t thinking about value right now, I suggest that you start. Value-based reimbursement is coming soon) and we know that a high percentage of vaginal hysterectomies are feasible in general gynecologic populations. Surgeons who perform vaginal hysterectomy are not magicians or better surgeons, just differently trained. We have to recognize that many, or even most, patients are candidates for vaginal hysterectomy.

Finally, when we look at robotics for benign disease, we spend more money than on other minimally invasive hysterectomy techniques but we don’t get better outcomes (J Minim Invasive Gynecol. 2010;17[6]:730-8and Eur J Obstet Gynecol Reprod Biol. 150[1]:92-6). Yet surgeons currently use robotics for 25% or more of benign hysterectomies.

What are we thinking and how can we afford to continue this?

We need to counsel our patients (and ourselves) that a total hysterectomy requires an incision in the vagina, and there can be a need for additional abdominal incisions of varying size and number. Fully informed consent must include a discussion of all types of hysterectomy including both patient and surgeon factors associated with the recommended route. Ultimately, the route of hysterectomy should be based on the patient and not the surgeon (Obstet Gynecol. 2014;124[3]:585-8).

It is easy to say, and supported by the evidence, that we should do more vaginal hysterectomies. It is also easy to note that the rate of vaginal hysterectomy has been stable to declining over the last 4 decades and that there are significant issues with residency training in gynecologic surgery (serious issues, but beyond the scope of this editorial).

So, what are we at SGS doing to support increased rates of vaginal hysterectomy? Every December we sponsor a postgraduate course on vaginal hysterectomy techniques. This is an excellent learning opportunity. (Visit www.sgsonline.org for more information regarding dates and costs). We’re starting partnerships with the American College of Obstetricians and Gynecologists (ACOG), the Foundation for Exxcellence in Women’s Health and others, to begin a “train the trainer” program to teach junior faculty how to do and teach vaginal hysterectomy. We’ve developed CREOG (Council on Resident Education in Obstetrics and Gynecology) modules to educate residents about the procedure, and we are in the process of communicating with residency and fellowship program directors about what else we can do to assist them with vaginal hysterectomy teaching. Other goals are to work with ACOG to develop quality metrics for hysterectomy and to develop physician-focused alternative payment models that recognize the value of vaginal hysterectomy.

I believe that in this country we should train for, incentivize, and insist upon a vaginal hysterectomy rate of at least 40% (this albeit arbitrary percentage is based upon the majority of vaginally parous women with uteri less than 12 weeks in size and a minority of the more difficult patients getting a vaginal hysterectomy). And before you say “it’s never been 40%,” please consider the famous quotation by Dr. William Mayo: “The best interest of the patient is the only interest to be considered.” Clearly, the best interest of the patient, if she is a candidate, is to have a vaginal hysterectomy. Our mission at SGS is to facilitate surgical education to make more patients candidates for vaginal hysterectomy so that we can achieve the 40% goal.

Dr. Walter is director of urogynecology and pelvic pain at The Permanente Medical Group, Roseville, Calif. He is also the immediate past president of the Society of Gynecologic Surgeons. He reported having no financial disclosures.

One of the great honors of my professional career was being nominated to the presidency of the Society of Gynecologic Surgeons and being given the opportunity to deliver the presidential address at the Society’s 42nd annual scientific meeting in Palm Springs, Calif.

One of the core principles of the SGS mission statement is supporting excellence in gynecologic surgery and, to that end, the main focus of my term was to address the decline in vaginal hysterectomy rates. What follows is an excerpt from my speech explaining the rationale for vaginal hysterectomy (VH) and steps the SGS is taking to reverse the decline.

Unfortunately, what is happening in today’s practice environment is declining use of vaginal hysterectomy, with concomitant increases in endoscopic hysterectomy, mostly with the use of robotic assistance. Being the president of a society previously known as the Vaginal Surgeons Society, it would not be surprising to hear that I have been accused of being “anti-robot.”

Nothing could be further from the truth.

When we talk about the surgical treatment of patients with endometrial and cervical cancer, I do not need a randomized clinical trial to know that not making a laparotomy incision is probably a good thing when you’re treating these patients. There are benefits to using robotic techniques in this subpopulation; it is cost effective due to the reduced morbidity and straight stick laparoscopy for these patients is difficult to perform; therefore it’s not been as widely published or performed. I believe that robotic hysterectomy for these disorders should be the standard of care. In this regard, I am pro robot (Gynecologic Oncol. 2015;138[2]:457-71).

On the other hand, I also don’t need a randomized trial (even though randomized trials exist) to know that if you have a choice to make, or not make, extra incisions during surgery, it’s better to not make the extra incisions.

It’s certainly not rocket science to know that a Zeppelin or Heaney clamp is orders of magnitude cheaper than equipment required to perform an endoscopic hysterectomy – $22.25 USD for instrument and $3.19 USD to process per case (Am J Obstet Gynecol. 2016;214[4]:S461-2]).

Level I evidence demonstrates that when compared to other minimally invasive hysterectomy techniques, vaginal hysterectomy is cheaper, the convalescence is stable or reduced, and the complication rates are lower (Cochrane Database Syst Rev. 2015 Aug. 12;8:CD003677).

Moreover, if you don’t place a port, you can’t get a port site complication (these complications are rare, but potentially serious when they occur). You can’t perforate the common iliac vein. You can’t put a Veress needle through the small bowel. You can’t get a Richter’s hernia. And finally, while you can get cuff dehiscence with vaginal hysterectomy, I’ve never seen it, and this is a real issue with the endoscopic approaches (Cochrane Database Syst Rev. 2012 Feb. 15;2:CD006583 ).

This isn’t just my opinion. Every major surgical society has recommended vaginal hysterectomy when technically feasible.

Of course, “technical feasibility” is the kicker and it’s important to ask what this means.

First, we have to look at what I call the hysterectomy continuum. There are the young, sexually-active women with uterovaginal procidentia where an endoscopic approach for sacral colpopexy might be considered. Then you have patients who are vaginally parous, have a mobile uterus less than 12 weeks in size, and have a basic gynecologic condition such as dysfunctional uterine bleeding, cervical intraepithelial neoplasia, or painful menses (this is about 40%-50% of patients when I reviewed internal North Valley Permanente Group data in 2012); these patients are certainly excellent candidates for vaginal hysterectomy. Then there are patients with 30-week-size fibroid uterus, three prior C-sections, and known stage 4 endometriosis (where an open or robotic approach would be justified).

Second, we have to address the contradictory data presented in the literature regarding vaginal hysterectomy rates. On one hand, we have data from large case series and randomized, controlled trials which demonstrate that it’s feasible to perform a high percentage of vaginal hysterectomies (Obstet Gynecol. 2004;103[6]:1321-5and Arch Gynecol Obstet. 2014;290[3]:485-91). On the other hand, 40 years of population data show the opposite (Obstet Gynecol. 2009;114[5]:1041-8).

In the pre-endoscopic era, 80% and 20% of hysterectomies were performed via the abdominal and vaginal routes, respectively. During the laparoscopic era, 64%, 22%, and 14% of hysterectomies were performed via the abdominal, vaginal, and laparoscopic routes, respectively. And during the current robotic era, it is now 32%, 16%, 28%, and 25% performed via the abdominal, vaginal, laparoscopic, and robotic routes, respectively.

During this 40-year time frame, despite data and recommendations that support vaginal hysterectomy, there has never been an obvious incentive to perform this procedure (e.g. to my knowledge, no one has ever been paid more to do a vaginal hysterectomy, or been prominently featured on a hospital’s website regarding his or her ability to perform an “incision-less” hysterectomy (Am J Obstet Gynecol. 2012;207[3]:174.e1-174.e7). Why weren’t and why aren’t we outraged about this? I have always been under the impression that cheaper and safer is better!

The first thing I hear to explain this – mostly from robotic surgeons and from the robotic surgery device sales representatives – is that the decline in the proportion of vaginal hysterectomies is irrelevant in that it has taken the robot to meaningfully reduce open hysterectomy rates. The other argument I hear – mostly from the laparoscopic surgeons – is that vaginal hysterectomy rates have not changed because most gynecologists cannot and will never be able to perform the procedure. So, what is the point of even discussing solutions?

I disagree with the laparoscopic and robotic surgeons. We should be outraged and do something to effect change. Vaginal hysterectomy offers better value (for surgeons who aren’t thinking about value right now, I suggest that you start. Value-based reimbursement is coming soon) and we know that a high percentage of vaginal hysterectomies are feasible in general gynecologic populations. Surgeons who perform vaginal hysterectomy are not magicians or better surgeons, just differently trained. We have to recognize that many, or even most, patients are candidates for vaginal hysterectomy.

Finally, when we look at robotics for benign disease, we spend more money than on other minimally invasive hysterectomy techniques but we don’t get better outcomes (J Minim Invasive Gynecol. 2010;17[6]:730-8and Eur J Obstet Gynecol Reprod Biol. 150[1]:92-6). Yet surgeons currently use robotics for 25% or more of benign hysterectomies.

What are we thinking and how can we afford to continue this?

We need to counsel our patients (and ourselves) that a total hysterectomy requires an incision in the vagina, and there can be a need for additional abdominal incisions of varying size and number. Fully informed consent must include a discussion of all types of hysterectomy including both patient and surgeon factors associated with the recommended route. Ultimately, the route of hysterectomy should be based on the patient and not the surgeon (Obstet Gynecol. 2014;124[3]:585-8).

It is easy to say, and supported by the evidence, that we should do more vaginal hysterectomies. It is also easy to note that the rate of vaginal hysterectomy has been stable to declining over the last 4 decades and that there are significant issues with residency training in gynecologic surgery (serious issues, but beyond the scope of this editorial).

So, what are we at SGS doing to support increased rates of vaginal hysterectomy? Every December we sponsor a postgraduate course on vaginal hysterectomy techniques. This is an excellent learning opportunity. (Visit www.sgsonline.org for more information regarding dates and costs). We’re starting partnerships with the American College of Obstetricians and Gynecologists (ACOG), the Foundation for Exxcellence in Women’s Health and others, to begin a “train the trainer” program to teach junior faculty how to do and teach vaginal hysterectomy. We’ve developed CREOG (Council on Resident Education in Obstetrics and Gynecology) modules to educate residents about the procedure, and we are in the process of communicating with residency and fellowship program directors about what else we can do to assist them with vaginal hysterectomy teaching. Other goals are to work with ACOG to develop quality metrics for hysterectomy and to develop physician-focused alternative payment models that recognize the value of vaginal hysterectomy.

I believe that in this country we should train for, incentivize, and insist upon a vaginal hysterectomy rate of at least 40% (this albeit arbitrary percentage is based upon the majority of vaginally parous women with uteri less than 12 weeks in size and a minority of the more difficult patients getting a vaginal hysterectomy). And before you say “it’s never been 40%,” please consider the famous quotation by Dr. William Mayo: “The best interest of the patient is the only interest to be considered.” Clearly, the best interest of the patient, if she is a candidate, is to have a vaginal hysterectomy. Our mission at SGS is to facilitate surgical education to make more patients candidates for vaginal hysterectomy so that we can achieve the 40% goal.

Dr. Walter is director of urogynecology and pelvic pain at The Permanente Medical Group, Roseville, Calif. He is also the immediate past president of the Society of Gynecologic Surgeons. He reported having no financial disclosures.

One of the great honors of my professional career was being nominated to the presidency of the Society of Gynecologic Surgeons and being given the opportunity to deliver the presidential address at the Society’s 42nd annual scientific meeting in Palm Springs, Calif.

One of the core principles of the SGS mission statement is supporting excellence in gynecologic surgery and, to that end, the main focus of my term was to address the decline in vaginal hysterectomy rates. What follows is an excerpt from my speech explaining the rationale for vaginal hysterectomy (VH) and steps the SGS is taking to reverse the decline.

Unfortunately, what is happening in today’s practice environment is declining use of vaginal hysterectomy, with concomitant increases in endoscopic hysterectomy, mostly with the use of robotic assistance. Being the president of a society previously known as the Vaginal Surgeons Society, it would not be surprising to hear that I have been accused of being “anti-robot.”

Nothing could be further from the truth.

When we talk about the surgical treatment of patients with endometrial and cervical cancer, I do not need a randomized clinical trial to know that not making a laparotomy incision is probably a good thing when you’re treating these patients. There are benefits to using robotic techniques in this subpopulation; it is cost effective due to the reduced morbidity and straight stick laparoscopy for these patients is difficult to perform; therefore it’s not been as widely published or performed. I believe that robotic hysterectomy for these disorders should be the standard of care. In this regard, I am pro robot (Gynecologic Oncol. 2015;138[2]:457-71).

On the other hand, I also don’t need a randomized trial (even though randomized trials exist) to know that if you have a choice to make, or not make, extra incisions during surgery, it’s better to not make the extra incisions.

It’s certainly not rocket science to know that a Zeppelin or Heaney clamp is orders of magnitude cheaper than equipment required to perform an endoscopic hysterectomy – $22.25 USD for instrument and $3.19 USD to process per case (Am J Obstet Gynecol. 2016;214[4]:S461-2]).

Level I evidence demonstrates that when compared to other minimally invasive hysterectomy techniques, vaginal hysterectomy is cheaper, the convalescence is stable or reduced, and the complication rates are lower (Cochrane Database Syst Rev. 2015 Aug. 12;8:CD003677).

Moreover, if you don’t place a port, you can’t get a port site complication (these complications are rare, but potentially serious when they occur). You can’t perforate the common iliac vein. You can’t put a Veress needle through the small bowel. You can’t get a Richter’s hernia. And finally, while you can get cuff dehiscence with vaginal hysterectomy, I’ve never seen it, and this is a real issue with the endoscopic approaches (Cochrane Database Syst Rev. 2012 Feb. 15;2:CD006583 ).

This isn’t just my opinion. Every major surgical society has recommended vaginal hysterectomy when technically feasible.

Of course, “technical feasibility” is the kicker and it’s important to ask what this means.

First, we have to look at what I call the hysterectomy continuum. There are the young, sexually-active women with uterovaginal procidentia where an endoscopic approach for sacral colpopexy might be considered. Then you have patients who are vaginally parous, have a mobile uterus less than 12 weeks in size, and have a basic gynecologic condition such as dysfunctional uterine bleeding, cervical intraepithelial neoplasia, or painful menses (this is about 40%-50% of patients when I reviewed internal North Valley Permanente Group data in 2012); these patients are certainly excellent candidates for vaginal hysterectomy. Then there are patients with 30-week-size fibroid uterus, three prior C-sections, and known stage 4 endometriosis (where an open or robotic approach would be justified).

Second, we have to address the contradictory data presented in the literature regarding vaginal hysterectomy rates. On one hand, we have data from large case series and randomized, controlled trials which demonstrate that it’s feasible to perform a high percentage of vaginal hysterectomies (Obstet Gynecol. 2004;103[6]:1321-5and Arch Gynecol Obstet. 2014;290[3]:485-91). On the other hand, 40 years of population data show the opposite (Obstet Gynecol. 2009;114[5]:1041-8).

In the pre-endoscopic era, 80% and 20% of hysterectomies were performed via the abdominal and vaginal routes, respectively. During the laparoscopic era, 64%, 22%, and 14% of hysterectomies were performed via the abdominal, vaginal, and laparoscopic routes, respectively. And during the current robotic era, it is now 32%, 16%, 28%, and 25% performed via the abdominal, vaginal, laparoscopic, and robotic routes, respectively.

During this 40-year time frame, despite data and recommendations that support vaginal hysterectomy, there has never been an obvious incentive to perform this procedure (e.g. to my knowledge, no one has ever been paid more to do a vaginal hysterectomy, or been prominently featured on a hospital’s website regarding his or her ability to perform an “incision-less” hysterectomy (Am J Obstet Gynecol. 2012;207[3]:174.e1-174.e7). Why weren’t and why aren’t we outraged about this? I have always been under the impression that cheaper and safer is better!

The first thing I hear to explain this – mostly from robotic surgeons and from the robotic surgery device sales representatives – is that the decline in the proportion of vaginal hysterectomies is irrelevant in that it has taken the robot to meaningfully reduce open hysterectomy rates. The other argument I hear – mostly from the laparoscopic surgeons – is that vaginal hysterectomy rates have not changed because most gynecologists cannot and will never be able to perform the procedure. So, what is the point of even discussing solutions?

I disagree with the laparoscopic and robotic surgeons. We should be outraged and do something to effect change. Vaginal hysterectomy offers better value (for surgeons who aren’t thinking about value right now, I suggest that you start. Value-based reimbursement is coming soon) and we know that a high percentage of vaginal hysterectomies are feasible in general gynecologic populations. Surgeons who perform vaginal hysterectomy are not magicians or better surgeons, just differently trained. We have to recognize that many, or even most, patients are candidates for vaginal hysterectomy.

Finally, when we look at robotics for benign disease, we spend more money than on other minimally invasive hysterectomy techniques but we don’t get better outcomes (J Minim Invasive Gynecol. 2010;17[6]:730-8and Eur J Obstet Gynecol Reprod Biol. 150[1]:92-6). Yet surgeons currently use robotics for 25% or more of benign hysterectomies.

What are we thinking and how can we afford to continue this?

We need to counsel our patients (and ourselves) that a total hysterectomy requires an incision in the vagina, and there can be a need for additional abdominal incisions of varying size and number. Fully informed consent must include a discussion of all types of hysterectomy including both patient and surgeon factors associated with the recommended route. Ultimately, the route of hysterectomy should be based on the patient and not the surgeon (Obstet Gynecol. 2014;124[3]:585-8).

It is easy to say, and supported by the evidence, that we should do more vaginal hysterectomies. It is also easy to note that the rate of vaginal hysterectomy has been stable to declining over the last 4 decades and that there are significant issues with residency training in gynecologic surgery (serious issues, but beyond the scope of this editorial).

So, what are we at SGS doing to support increased rates of vaginal hysterectomy? Every December we sponsor a postgraduate course on vaginal hysterectomy techniques. This is an excellent learning opportunity. (Visit www.sgsonline.org for more information regarding dates and costs). We’re starting partnerships with the American College of Obstetricians and Gynecologists (ACOG), the Foundation for Exxcellence in Women’s Health and others, to begin a “train the trainer” program to teach junior faculty how to do and teach vaginal hysterectomy. We’ve developed CREOG (Council on Resident Education in Obstetrics and Gynecology) modules to educate residents about the procedure, and we are in the process of communicating with residency and fellowship program directors about what else we can do to assist them with vaginal hysterectomy teaching. Other goals are to work with ACOG to develop quality metrics for hysterectomy and to develop physician-focused alternative payment models that recognize the value of vaginal hysterectomy.

I believe that in this country we should train for, incentivize, and insist upon a vaginal hysterectomy rate of at least 40% (this albeit arbitrary percentage is based upon the majority of vaginally parous women with uteri less than 12 weeks in size and a minority of the more difficult patients getting a vaginal hysterectomy). And before you say “it’s never been 40%,” please consider the famous quotation by Dr. William Mayo: “The best interest of the patient is the only interest to be considered.” Clearly, the best interest of the patient, if she is a candidate, is to have a vaginal hysterectomy. Our mission at SGS is to facilitate surgical education to make more patients candidates for vaginal hysterectomy so that we can achieve the 40% goal.

Dr. Walter is director of urogynecology and pelvic pain at The Permanente Medical Group, Roseville, Calif. He is also the immediate past president of the Society of Gynecologic Surgeons. He reported having no financial disclosures.

The U.S. Department of Agriculture has made $6 million available through its Agriculture and Food Research Initiative to fund research on antimicrobial resistance.

“The research projects funded through this announcement will help us succeed in our efforts to preserve the effectiveness of antibiotics and protect public health,” said U.S. Agriculture Secretary Tom Vilsack in a statement.

©David Parr/thinkstockphotos.com

The funding is authorized by the 2014 Farm Bill and administered by the USDA’s National Institute of Food and Agriculture. Secretary Vilsack said it is one of many ways that the USDA supports the Combating Antimicrobial Resistant Bacteria (CARB) National Action Plan and work of the Task Force for Combating Antibiotic Resistance, which the USDA cochairs. The program priority is to promote the development of sustainable and integrated food safety strategies that reduce public health risks along the entire food chain.

According to the USDA announcement, applications for funding must address one or more of the following:

• Develop novel systems approaches to investigate the ecology of microbial resistance microbes and gene reservoirs in the environment in animals, crops, food products, or farm-raised aquaculture products.

• Develop, evaluate, and implement effective and sustainable resources and strategies, to include alternative practices, techniques, technologies, or tools that mitigate emergence, spread, or persistence of antimicrobial-resistant pathogens within the agricultural ecosystem, in animals, crops, and food.

• Identify critical control points for mitigating antimicrobial resistance in the pre- and postharvest food production environment.

• Design innovative training, education, and outreach resources (including Web-based resources) that can be adapted by users across the food chain, including policy makers, producers, processors, retailers, and consumers.

• Design and conduct studies that evaluate the impact and efficacy of proposed research, education, and extension/outreach interventions on antimicrobial resistance across the food chain, from primary producers to primary consumers.

Since 2009, more than $82 million in food safety research and extension grants has been awarded through the Agriculture and Food Research Initiative, including $3.4 million in fiscal year 2015 for antimicrobial resistance. Previously funded projects include a State University of New York project evaluating critical control points in dairy farm operations and a Texas A&M University project to develop science-based decision aids related to antibiotic stewardship.

Applications are due Aug. 3, 2016. See the request for applications for more information.

[email protected]

On Twitter @richpizzi

The U.S. Department of Agriculture has made $6 million available through its Agriculture and Food Research Initiative to fund research on antimicrobial resistance.

“The research projects funded through this announcement will help us succeed in our efforts to preserve the effectiveness of antibiotics and protect public health,” said U.S. Agriculture Secretary Tom Vilsack in a statement.

©David Parr/thinkstockphotos.com

The funding is authorized by the 2014 Farm Bill and administered by the USDA’s National Institute of Food and Agriculture. Secretary Vilsack said it is one of many ways that the USDA supports the Combating Antimicrobial Resistant Bacteria (CARB) National Action Plan and work of the Task Force for Combating Antibiotic Resistance, which the USDA cochairs. The program priority is to promote the development of sustainable and integrated food safety strategies that reduce public health risks along the entire food chain.

According to the USDA announcement, applications for funding must address one or more of the following:

• Develop novel systems approaches to investigate the ecology of microbial resistance microbes and gene reservoirs in the environment in animals, crops, food products, or farm-raised aquaculture products.

• Develop, evaluate, and implement effective and sustainable resources and strategies, to include alternative practices, techniques, technologies, or tools that mitigate emergence, spread, or persistence of antimicrobial-resistant pathogens within the agricultural ecosystem, in animals, crops, and food.

• Identify critical control points for mitigating antimicrobial resistance in the pre- and postharvest food production environment.

• Design innovative training, education, and outreach resources (including Web-based resources) that can be adapted by users across the food chain, including policy makers, producers, processors, retailers, and consumers.

• Design and conduct studies that evaluate the impact and efficacy of proposed research, education, and extension/outreach interventions on antimicrobial resistance across the food chain, from primary producers to primary consumers.

Since 2009, more than $82 million in food safety research and extension grants has been awarded through the Agriculture and Food Research Initiative, including $3.4 million in fiscal year 2015 for antimicrobial resistance. Previously funded projects include a State University of New York project evaluating critical control points in dairy farm operations and a Texas A&M University project to develop science-based decision aids related to antibiotic stewardship.

Applications are due Aug. 3, 2016. See the request for applications for more information.

[email protected]

On Twitter @richpizzi

The U.S. Department of Agriculture has made $6 million available through its Agriculture and Food Research Initiative to fund research on antimicrobial resistance.

“The research projects funded through this announcement will help us succeed in our efforts to preserve the effectiveness of antibiotics and protect public health,” said U.S. Agriculture Secretary Tom Vilsack in a statement.

©David Parr/thinkstockphotos.com

The funding is authorized by the 2014 Farm Bill and administered by the USDA’s National Institute of Food and Agriculture. Secretary Vilsack said it is one of many ways that the USDA supports the Combating Antimicrobial Resistant Bacteria (CARB) National Action Plan and work of the Task Force for Combating Antibiotic Resistance, which the USDA cochairs. The program priority is to promote the development of sustainable and integrated food safety strategies that reduce public health risks along the entire food chain.

According to the USDA announcement, applications for funding must address one or more of the following:

• Develop novel systems approaches to investigate the ecology of microbial resistance microbes and gene reservoirs in the environment in animals, crops, food products, or farm-raised aquaculture products.

• Develop, evaluate, and implement effective and sustainable resources and strategies, to include alternative practices, techniques, technologies, or tools that mitigate emergence, spread, or persistence of antimicrobial-resistant pathogens within the agricultural ecosystem, in animals, crops, and food.

• Identify critical control points for mitigating antimicrobial resistance in the pre- and postharvest food production environment.

• Design innovative training, education, and outreach resources (including Web-based resources) that can be adapted by users across the food chain, including policy makers, producers, processors, retailers, and consumers.

• Design and conduct studies that evaluate the impact and efficacy of proposed research, education, and extension/outreach interventions on antimicrobial resistance across the food chain, from primary producers to primary consumers.

Since 2009, more than $82 million in food safety research and extension grants has been awarded through the Agriculture and Food Research Initiative, including $3.4 million in fiscal year 2015 for antimicrobial resistance. Previously funded projects include a State University of New York project evaluating critical control points in dairy farm operations and a Texas A&M University project to develop science-based decision aids related to antibiotic stewardship.

Applications are due Aug. 3, 2016. See the request for applications for more information.

[email protected]

On Twitter @richpizzi

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

[email protected]

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

[email protected]

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

[email protected]

Lymphomatoid papulosis (LyP) is a clinicopathologic variant of CD30⁺ primary cutaneous T-cell lymphoproliferative disorder characterized by a chronic, recurrent, self-healing eruption of papules and small nodules. From a clinical point of view, LyP is not considered a malignant disorder despite demonstration of clonality in most cases.¹ From a histopathologic point of view, there are 5 types of LyP: (1) type A, the most common type, which is characterized by a wedge-shaped infiltrate composed of clustered large atypical cells admixed with neutrophils, eosinophils, histiocytes, and small lymphocytes; (2) type B, a rare variant characterized by a bandlike infiltrate of small- to medium-sized pleomorphic and hyperchromatic lymphocytes involving the superficial dermis with epidermotropism; (3) type C, which consists of a nodular infiltrate of large atypical cells with a cohesive arrangement closely similar to anaplastic large-cell lymphoma; (4) type D, a variant with histopathologic features that resemble primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma, but neoplastic cells express CD30 and a T-cell cytotoxic phenotype (βF1⁺, CD3+, CD4^‒, CD8⁺), and follow-up usually does not reveal development of systemic involvement or signs of other cutaneous lymphomas²; and (5) type E, which is characterized by oligolesional papules that rapidly ulcerate and evolve into large, necrotic, escharlike lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small- to medium-sized atypical lymphocytes expressing CD30 and frequently CD8.³

The clinical appearance of LyP usually is polymorphic, with lesions in different stages of evolution scattered all over the skin; however, the lesions are occasionally localized only to one area of the skin, the so-called regional or agminated LyP.^4-14 We report a case of regional LyP that exclusively involved the skin of the left breast, which had previously received radiotherapy for treatment of breast carcinoma. Lymphomatoid papulosis with cutaneous lesions involving only an area of irradiated skin is rare.

Case Report

A 59-year-old woman presented with new-onset cutaneous lesions on the left breast. The patient had a history of invasive ductal carcinoma of the left breast, which had been treated 5 years prior with a partial mastectomy and radiotherapy (10 Gy per week for 5 consecutive weeks [50 Gy total]). Physical examination revealed a large nodular lesion with a necrotic surface on the upper half of the left breast as well as 3 small papular lesions with eroded surfaces on the lower half of the breast (Figure 1). A clinical diagnosis of cutaneous metastases from breast carcinoma was suspected.

Biopsies from one small papule and the large nodular lesion showed similar findings consisting of a necrotic epidermis covered by crusts and a wedge-shaped infiltrate involving the superficial dermis (Figure 2A). The infiltrate was mostly composed of large atypical mononuclear cells with oval to kidney-shaped nuclei, prominent nucleoli, and ample basophilic cytoplasm. Many mitotic figures were seen within the infiltrate (Figure 2B). The infiltrate of atypical cells was admixed with small lymphocytes, histiocytes, and some eosinophils. Immunohistochemically, the large atypical cells expressed CD2, CD3, CD4, CD45, CD30, and epithelial membrane antigen (Figures 2C and 2D). A few atypical cells also expressed CD8 and T-cell intracellular antigen 1. Approximately 60% of the nuclei of the atypical cells showed MIB-1 positivity, while CD20, CD56, AE1/AE3, S-100 protein, CD34, and CD31 were negative. The anaplastic lymphoma kinase was not expressed in atypical cells. Monoclonal rearrangement of the γ T-cell receptor was demonstrated on polymerase chain reaction. Physical examination showed no lymphadenopathy in any lymph node chains. Computed tomography of the chest and abdomen failed to demonstrate systemic involvement. On the basis of these clinical, histologic, immunohistochemical, and molecular results, a diagnosis of type A regional LyP was established.

The patient was treated with 2 daily applications of clobetasol propionate cream 0.5 mg/g and 10 mg of oral methotrexate per week for 4 weeks. After 4 weeks of treatment, the lesions on the left breast had resolved leaving slightly atrophic scars. Six months later, an episode of recurrent papular lesions occurred in the same area and responded to the same treatment, but no systemic involvement had been found.

Comment

Regional LyP is a rare variant, with only a few reported cases in the literature.^4-18 Scarisbrick et al⁴ originally reported 4 patients with LyP limited to specific regions. Interestingly, one of the patients had mycosis fungoides and the LyP lesions were confined to the same region where the mycosis fungoides lesions were observed.⁴ In a review of LyP in patients from the Netherlands (n=118), lesions limited to a specific region of the body were observed in 13% of cases.⁵ Cases of LyP limited to acral skin also have been reported.^6-8 Heald et al⁹ described 7 patients who had continuing eruptions of papulonodules with histopathologic features of LyP within well-circumscribed areas of the skin. The investigators interpreted this localized variant of LyP as an equivalent of the limited plaque stage of mycosis fungoides. Interestingly, one of the patients with LyP eventually developed plaques of mycosis fungoides in other areas of the skin not involved by LyP.⁹ Sharma et al¹⁰ described an additional example of regional LyP, and Nakahigashi et al¹¹ described a patient with tumor-stage mycosis fungoides who subsequently developed regional LyP involving the right side of the chest. Kim et al¹² described a patient with recurrent episodes of regional LyP exclusively involving the periorbital skin, and Torrelo et al¹³ reported a 12-year-old boy with persistent lesions of LyP involving the skin of the right side of the abdomen. Coelho et al¹⁴ reported a 13-year-old adolescent girl who presented with recurrent papules of LyP exclusively involving the left upper arm. Buder et al¹⁵ reported a case of LyP limited to Becker melanosis. Shang et al¹⁶ described an additional caseof regional LyP that was successfully controlled by interferon alfa-2b and nitrogen mustard solution. Haus et al¹⁷ reported type A LyP confined to the cutaneous area within a red tattoo. Finally, Wang et al¹⁸ reported a case of regional LyP in association with pseudoepitheliomatous hyperplasia

Several dermatoses may appear as specific isomorphic responses to various external stimuli, and it is possible that radiotherapy induces some damage that favors the location of the lesions because the irradiated skin behaves as a locus minoris resistentiae. Pemphigus vulgaris,^19,20 Sweet syndrome,²¹ cutaneous angiosarcoma,^22-32 and cutaneous metastases from malignant melanoma also have been reported to be confined to irradiated skin.³³ However, in our PubMed search of articles indexed for MEDLINE using the terms lymphomatoid papules and regional, none of the previously reported cases of regional LyP had a history of radiotherapy, and in no instance did the lesions develop on a previously irradiated area of the skin.^4-18 The localization of the lesions in our patient could have been the result of the so-called radiation recall phenomenon. Recall dermatitis is defined as a skin reaction in a previously irradiated field, usually subsequent to the administration of cytotoxic drugs or antibiotics.³⁴ It may appear days to years after exposure to ionizing radiation and has mostly been associated with chemotherapy drugs, but recall dermatitis is neither exclusive of chemotherapy medications nor strictly radiotherapy induced. The concept of recall dermatitis has been expanded beyond radiation recall dermatitis to include dermatitis induced by other stimuli, including other drugs, contact irritants, and UV radiation, as well as residual herpes zoster. Nevertheless, in recall dermatitis the triggering drug or agent recalls a prior dermatitis in the involved area, such as sunburn or radiodermatitis. In our patient, there was no history of LyP prior to irradiation of the left breast; therefore, the most plausible interpretation of the peculiar localization of the lesions in our patient seems to be that the eruption resulted as expression of a locus minoris resistentiae.

Distinction between primary cutaneous anaplastic large-cell lymphoma and LyP may be difficult because the histopathologic and immunophenotypic features may overlap. In our case, the presence of several papular lesions and one large nodule are more consistent, from a clinical point of view, with a diagnosis of LyP rather than primary cutaneous anaplastic large-cell lymphoma, which usually presents with a solitary and often large, ulcerated, reddish brown tumor. In our patient, the absence of lymphadenopathy, negative results of the computed tomography of the chest and abdomen, and lack of expression for anaplastic lymphoma kinase in atypical cells of the infiltrate militate against a diagnosis of secondary cutaneous involvement from nodal disease.

The histopathologic differential diagnosis of the current case also included cutaneous CD30⁺ epithelioid angiosarcoma of the breast. Weed and Folpe³⁵ reported the case of an 85-year-old woman who developed a CD30⁺ epithelioid angiosarcoma on the breast after undergoing breast-conserving surgery and adjuvant radiotherapy for treatment of an infiltrating ductal carcinoma of the breast. Histopathology showed a diffuse replacement of the dermis by a highly malignant-appearing epithelioid neoplasm growing in a solid sheet. Neoplastic cells expressed strong CD30 immunoreactivity with absence of immunoexpression for cytokeratins, S-100 protein, and CD45. Additional immunostaining demonstrated that neoplastic cells also expressed strong immunoreactivity for CD31 and the friend leukemia virus integration 1 gene, FLI-1, and focal positivity for von Willebrand factor, supporting a diagnosis of epithelioid angiosarcoma.³⁵ In our patient, CD34 and CD31 were negative, which ruled out the endothelial nature of neoplastic cells.

Conclusion

In summary, we report an example of regional LyP limited to the left breast of a woman with a history of partial mastectomy and adjuvant radiotherapy for treatment of invasive ductal breast carcinoma. It is a rare case of regional LyP exclusively involving an irradiated area of the skin.

Lymphomatoid papulosis (LyP) is a clinicopathologic variant of CD30⁺ primary cutaneous T-cell lymphoproliferative disorder characterized by a chronic, recurrent, self-healing eruption of papules and small nodules. From a clinical point of view, LyP is not considered a malignant disorder despite demonstration of clonality in most cases.¹ From a histopathologic point of view, there are 5 types of LyP: (1) type A, the most common type, which is characterized by a wedge-shaped infiltrate composed of clustered large atypical cells admixed with neutrophils, eosinophils, histiocytes, and small lymphocytes; (2) type B, a rare variant characterized by a bandlike infiltrate of small- to medium-sized pleomorphic and hyperchromatic lymphocytes involving the superficial dermis with epidermotropism; (3) type C, which consists of a nodular infiltrate of large atypical cells with a cohesive arrangement closely similar to anaplastic large-cell lymphoma; (4) type D, a variant with histopathologic features that resemble primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma, but neoplastic cells express CD30 and a T-cell cytotoxic phenotype (βF1⁺, CD3+, CD4^‒, CD8⁺), and follow-up usually does not reveal development of systemic involvement or signs of other cutaneous lymphomas²; and (5) type E, which is characterized by oligolesional papules that rapidly ulcerate and evolve into large, necrotic, escharlike lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small- to medium-sized atypical lymphocytes expressing CD30 and frequently CD8.³

The clinical appearance of LyP usually is polymorphic, with lesions in different stages of evolution scattered all over the skin; however, the lesions are occasionally localized only to one area of the skin, the so-called regional or agminated LyP.^4-14 We report a case of regional LyP that exclusively involved the skin of the left breast, which had previously received radiotherapy for treatment of breast carcinoma. Lymphomatoid papulosis with cutaneous lesions involving only an area of irradiated skin is rare.

Case Report

A 59-year-old woman presented with new-onset cutaneous lesions on the left breast. The patient had a history of invasive ductal carcinoma of the left breast, which had been treated 5 years prior with a partial mastectomy and radiotherapy (10 Gy per week for 5 consecutive weeks [50 Gy total]). Physical examination revealed a large nodular lesion with a necrotic surface on the upper half of the left breast as well as 3 small papular lesions with eroded surfaces on the lower half of the breast (Figure 1). A clinical diagnosis of cutaneous metastases from breast carcinoma was suspected.

Biopsies from one small papule and the large nodular lesion showed similar findings consisting of a necrotic epidermis covered by crusts and a wedge-shaped infiltrate involving the superficial dermis (Figure 2A). The infiltrate was mostly composed of large atypical mononuclear cells with oval to kidney-shaped nuclei, prominent nucleoli, and ample basophilic cytoplasm. Many mitotic figures were seen within the infiltrate (Figure 2B). The infiltrate of atypical cells was admixed with small lymphocytes, histiocytes, and some eosinophils. Immunohistochemically, the large atypical cells expressed CD2, CD3, CD4, CD45, CD30, and epithelial membrane antigen (Figures 2C and 2D). A few atypical cells also expressed CD8 and T-cell intracellular antigen 1. Approximately 60% of the nuclei of the atypical cells showed MIB-1 positivity, while CD20, CD56, AE1/AE3, S-100 protein, CD34, and CD31 were negative. The anaplastic lymphoma kinase was not expressed in atypical cells. Monoclonal rearrangement of the γ T-cell receptor was demonstrated on polymerase chain reaction. Physical examination showed no lymphadenopathy in any lymph node chains. Computed tomography of the chest and abdomen failed to demonstrate systemic involvement. On the basis of these clinical, histologic, immunohistochemical, and molecular results, a diagnosis of type A regional LyP was established.

The patient was treated with 2 daily applications of clobetasol propionate cream 0.5 mg/g and 10 mg of oral methotrexate per week for 4 weeks. After 4 weeks of treatment, the lesions on the left breast had resolved leaving slightly atrophic scars. Six months later, an episode of recurrent papular lesions occurred in the same area and responded to the same treatment, but no systemic involvement had been found.

Comment

Regional LyP is a rare variant, with only a few reported cases in the literature.^4-18 Scarisbrick et al⁴ originally reported 4 patients with LyP limited to specific regions. Interestingly, one of the patients had mycosis fungoides and the LyP lesions were confined to the same region where the mycosis fungoides lesions were observed.⁴ In a review of LyP in patients from the Netherlands (n=118), lesions limited to a specific region of the body were observed in 13% of cases.⁵ Cases of LyP limited to acral skin also have been reported.^6-8 Heald et al⁹ described 7 patients who had continuing eruptions of papulonodules with histopathologic features of LyP within well-circumscribed areas of the skin. The investigators interpreted this localized variant of LyP as an equivalent of the limited plaque stage of mycosis fungoides. Interestingly, one of the patients with LyP eventually developed plaques of mycosis fungoides in other areas of the skin not involved by LyP.⁹ Sharma et al¹⁰ described an additional example of regional LyP, and Nakahigashi et al¹¹ described a patient with tumor-stage mycosis fungoides who subsequently developed regional LyP involving the right side of the chest. Kim et al¹² described a patient with recurrent episodes of regional LyP exclusively involving the periorbital skin, and Torrelo et al¹³ reported a 12-year-old boy with persistent lesions of LyP involving the skin of the right side of the abdomen. Coelho et al¹⁴ reported a 13-year-old adolescent girl who presented with recurrent papules of LyP exclusively involving the left upper arm. Buder et al¹⁵ reported a case of LyP limited to Becker melanosis. Shang et al¹⁶ described an additional caseof regional LyP that was successfully controlled by interferon alfa-2b and nitrogen mustard solution. Haus et al¹⁷ reported type A LyP confined to the cutaneous area within a red tattoo. Finally, Wang et al¹⁸ reported a case of regional LyP in association with pseudoepitheliomatous hyperplasia

Several dermatoses may appear as specific isomorphic responses to various external stimuli, and it is possible that radiotherapy induces some damage that favors the location of the lesions because the irradiated skin behaves as a locus minoris resistentiae. Pemphigus vulgaris,^19,20 Sweet syndrome,²¹ cutaneous angiosarcoma,^22-32 and cutaneous metastases from malignant melanoma also have been reported to be confined to irradiated skin.³³ However, in our PubMed search of articles indexed for MEDLINE using the terms lymphomatoid papules and regional, none of the previously reported cases of regional LyP had a history of radiotherapy, and in no instance did the lesions develop on a previously irradiated area of the skin.^4-18 The localization of the lesions in our patient could have been the result of the so-called radiation recall phenomenon. Recall dermatitis is defined as a skin reaction in a previously irradiated field, usually subsequent to the administration of cytotoxic drugs or antibiotics.³⁴ It may appear days to years after exposure to ionizing radiation and has mostly been associated with chemotherapy drugs, but recall dermatitis is neither exclusive of chemotherapy medications nor strictly radiotherapy induced. The concept of recall dermatitis has been expanded beyond radiation recall dermatitis to include dermatitis induced by other stimuli, including other drugs, contact irritants, and UV radiation, as well as residual herpes zoster. Nevertheless, in recall dermatitis the triggering drug or agent recalls a prior dermatitis in the involved area, such as sunburn or radiodermatitis. In our patient, there was no history of LyP prior to irradiation of the left breast; therefore, the most plausible interpretation of the peculiar localization of the lesions in our patient seems to be that the eruption resulted as expression of a locus minoris resistentiae.

Distinction between primary cutaneous anaplastic large-cell lymphoma and LyP may be difficult because the histopathologic and immunophenotypic features may overlap. In our case, the presence of several papular lesions and one large nodule are more consistent, from a clinical point of view, with a diagnosis of LyP rather than primary cutaneous anaplastic large-cell lymphoma, which usually presents with a solitary and often large, ulcerated, reddish brown tumor. In our patient, the absence of lymphadenopathy, negative results of the computed tomography of the chest and abdomen, and lack of expression for anaplastic lymphoma kinase in atypical cells of the infiltrate militate against a diagnosis of secondary cutaneous involvement from nodal disease.

The histopathologic differential diagnosis of the current case also included cutaneous CD30⁺ epithelioid angiosarcoma of the breast. Weed and Folpe³⁵ reported the case of an 85-year-old woman who developed a CD30⁺ epithelioid angiosarcoma on the breast after undergoing breast-conserving surgery and adjuvant radiotherapy for treatment of an infiltrating ductal carcinoma of the breast. Histopathology showed a diffuse replacement of the dermis by a highly malignant-appearing epithelioid neoplasm growing in a solid sheet. Neoplastic cells expressed strong CD30 immunoreactivity with absence of immunoexpression for cytokeratins, S-100 protein, and CD45. Additional immunostaining demonstrated that neoplastic cells also expressed strong immunoreactivity for CD31 and the friend leukemia virus integration 1 gene, FLI-1, and focal positivity for von Willebrand factor, supporting a diagnosis of epithelioid angiosarcoma.³⁵ In our patient, CD34 and CD31 were negative, which ruled out the endothelial nature of neoplastic cells.

Conclusion

In summary, we report an example of regional LyP limited to the left breast of a woman with a history of partial mastectomy and adjuvant radiotherapy for treatment of invasive ductal breast carcinoma. It is a rare case of regional LyP exclusively involving an irradiated area of the skin.

Lymphomatoid papulosis (LyP) is a clinicopathologic variant of CD30⁺ primary cutaneous T-cell lymphoproliferative disorder characterized by a chronic, recurrent, self-healing eruption of papules and small nodules. From a clinical point of view, LyP is not considered a malignant disorder despite demonstration of clonality in most cases.¹ From a histopathologic point of view, there are 5 types of LyP: (1) type A, the most common type, which is characterized by a wedge-shaped infiltrate composed of clustered large atypical cells admixed with neutrophils, eosinophils, histiocytes, and small lymphocytes; (2) type B, a rare variant characterized by a bandlike infiltrate of small- to medium-sized pleomorphic and hyperchromatic lymphocytes involving the superficial dermis with epidermotropism; (3) type C, which consists of a nodular infiltrate of large atypical cells with a cohesive arrangement closely similar to anaplastic large-cell lymphoma; (4) type D, a variant with histopathologic features that resemble primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma, but neoplastic cells express CD30 and a T-cell cytotoxic phenotype (βF1⁺, CD3+, CD4^‒, CD8⁺), and follow-up usually does not reveal development of systemic involvement or signs of other cutaneous lymphomas²; and (5) type E, which is characterized by oligolesional papules that rapidly ulcerate and evolve into large, necrotic, escharlike lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small- to medium-sized atypical lymphocytes expressing CD30 and frequently CD8.³

The clinical appearance of LyP usually is polymorphic, with lesions in different stages of evolution scattered all over the skin; however, the lesions are occasionally localized only to one area of the skin, the so-called regional or agminated LyP.^4-14 We report a case of regional LyP that exclusively involved the skin of the left breast, which had previously received radiotherapy for treatment of breast carcinoma. Lymphomatoid papulosis with cutaneous lesions involving only an area of irradiated skin is rare.

Case Report

A 59-year-old woman presented with new-onset cutaneous lesions on the left breast. The patient had a history of invasive ductal carcinoma of the left breast, which had been treated 5 years prior with a partial mastectomy and radiotherapy (10 Gy per week for 5 consecutive weeks [50 Gy total]). Physical examination revealed a large nodular lesion with a necrotic surface on the upper half of the left breast as well as 3 small papular lesions with eroded surfaces on the lower half of the breast (Figure 1). A clinical diagnosis of cutaneous metastases from breast carcinoma was suspected.

Biopsies from one small papule and the large nodular lesion showed similar findings consisting of a necrotic epidermis covered by crusts and a wedge-shaped infiltrate involving the superficial dermis (Figure 2A). The infiltrate was mostly composed of large atypical mononuclear cells with oval to kidney-shaped nuclei, prominent nucleoli, and ample basophilic cytoplasm. Many mitotic figures were seen within the infiltrate (Figure 2B). The infiltrate of atypical cells was admixed with small lymphocytes, histiocytes, and some eosinophils. Immunohistochemically, the large atypical cells expressed CD2, CD3, CD4, CD45, CD30, and epithelial membrane antigen (Figures 2C and 2D). A few atypical cells also expressed CD8 and T-cell intracellular antigen 1. Approximately 60% of the nuclei of the atypical cells showed MIB-1 positivity, while CD20, CD56, AE1/AE3, S-100 protein, CD34, and CD31 were negative. The anaplastic lymphoma kinase was not expressed in atypical cells. Monoclonal rearrangement of the γ T-cell receptor was demonstrated on polymerase chain reaction. Physical examination showed no lymphadenopathy in any lymph node chains. Computed tomography of the chest and abdomen failed to demonstrate systemic involvement. On the basis of these clinical, histologic, immunohistochemical, and molecular results, a diagnosis of type A regional LyP was established.

The patient was treated with 2 daily applications of clobetasol propionate cream 0.5 mg/g and 10 mg of oral methotrexate per week for 4 weeks. After 4 weeks of treatment, the lesions on the left breast had resolved leaving slightly atrophic scars. Six months later, an episode of recurrent papular lesions occurred in the same area and responded to the same treatment, but no systemic involvement had been found.

Comment

Regional LyP is a rare variant, with only a few reported cases in the literature.^4-18 Scarisbrick et al⁴ originally reported 4 patients with LyP limited to specific regions. Interestingly, one of the patients had mycosis fungoides and the LyP lesions were confined to the same region where the mycosis fungoides lesions were observed.⁴ In a review of LyP in patients from the Netherlands (n=118), lesions limited to a specific region of the body were observed in 13% of cases.⁵ Cases of LyP limited to acral skin also have been reported.^6-8 Heald et al⁹ described 7 patients who had continuing eruptions of papulonodules with histopathologic features of LyP within well-circumscribed areas of the skin. The investigators interpreted this localized variant of LyP as an equivalent of the limited plaque stage of mycosis fungoides. Interestingly, one of the patients with LyP eventually developed plaques of mycosis fungoides in other areas of the skin not involved by LyP.⁹ Sharma et al¹⁰ described an additional example of regional LyP, and Nakahigashi et al¹¹ described a patient with tumor-stage mycosis fungoides who subsequently developed regional LyP involving the right side of the chest. Kim et al¹² described a patient with recurrent episodes of regional LyP exclusively involving the periorbital skin, and Torrelo et al¹³ reported a 12-year-old boy with persistent lesions of LyP involving the skin of the right side of the abdomen. Coelho et al¹⁴ reported a 13-year-old adolescent girl who presented with recurrent papules of LyP exclusively involving the left upper arm. Buder et al¹⁵ reported a case of LyP limited to Becker melanosis. Shang et al¹⁶ described an additional caseof regional LyP that was successfully controlled by interferon alfa-2b and nitrogen mustard solution. Haus et al¹⁷ reported type A LyP confined to the cutaneous area within a red tattoo. Finally, Wang et al¹⁸ reported a case of regional LyP in association with pseudoepitheliomatous hyperplasia

Several dermatoses may appear as specific isomorphic responses to various external stimuli, and it is possible that radiotherapy induces some damage that favors the location of the lesions because the irradiated skin behaves as a locus minoris resistentiae. Pemphigus vulgaris,^19,20 Sweet syndrome,²¹ cutaneous angiosarcoma,^22-32 and cutaneous metastases from malignant melanoma also have been reported to be confined to irradiated skin.³³ However, in our PubMed search of articles indexed for MEDLINE using the terms lymphomatoid papules and regional, none of the previously reported cases of regional LyP had a history of radiotherapy, and in no instance did the lesions develop on a previously irradiated area of the skin.^4-18 The localization of the lesions in our patient could have been the result of the so-called radiation recall phenomenon. Recall dermatitis is defined as a skin reaction in a previously irradiated field, usually subsequent to the administration of cytotoxic drugs or antibiotics.³⁴ It may appear days to years after exposure to ionizing radiation and has mostly been associated with chemotherapy drugs, but recall dermatitis is neither exclusive of chemotherapy medications nor strictly radiotherapy induced. The concept of recall dermatitis has been expanded beyond radiation recall dermatitis to include dermatitis induced by other stimuli, including other drugs, contact irritants, and UV radiation, as well as residual herpes zoster. Nevertheless, in recall dermatitis the triggering drug or agent recalls a prior dermatitis in the involved area, such as sunburn or radiodermatitis. In our patient, there was no history of LyP prior to irradiation of the left breast; therefore, the most plausible interpretation of the peculiar localization of the lesions in our patient seems to be that the eruption resulted as expression of a locus minoris resistentiae.

Distinction between primary cutaneous anaplastic large-cell lymphoma and LyP may be difficult because the histopathologic and immunophenotypic features may overlap. In our case, the presence of several papular lesions and one large nodule are more consistent, from a clinical point of view, with a diagnosis of LyP rather than primary cutaneous anaplastic large-cell lymphoma, which usually presents with a solitary and often large, ulcerated, reddish brown tumor. In our patient, the absence of lymphadenopathy, negative results of the computed tomography of the chest and abdomen, and lack of expression for anaplastic lymphoma kinase in atypical cells of the infiltrate militate against a diagnosis of secondary cutaneous involvement from nodal disease.

The histopathologic differential diagnosis of the current case also included cutaneous CD30⁺ epithelioid angiosarcoma of the breast. Weed and Folpe³⁵ reported the case of an 85-year-old woman who developed a CD30⁺ epithelioid angiosarcoma on the breast after undergoing breast-conserving surgery and adjuvant radiotherapy for treatment of an infiltrating ductal carcinoma of the breast. Histopathology showed a diffuse replacement of the dermis by a highly malignant-appearing epithelioid neoplasm growing in a solid sheet. Neoplastic cells expressed strong CD30 immunoreactivity with absence of immunoexpression for cytokeratins, S-100 protein, and CD45. Additional immunostaining demonstrated that neoplastic cells also expressed strong immunoreactivity for CD31 and the friend leukemia virus integration 1 gene, FLI-1, and focal positivity for von Willebrand factor, supporting a diagnosis of epithelioid angiosarcoma.³⁵ In our patient, CD34 and CD31 were negative, which ruled out the endothelial nature of neoplastic cells.

Conclusion

In summary, we report an example of regional LyP limited to the left breast of a woman with a history of partial mastectomy and adjuvant radiotherapy for treatment of invasive ductal breast carcinoma. It is a rare case of regional LyP exclusively involving an irradiated area of the skin.

To the Editor:

Onychomadesis is characterized by separation of the nail plate from the matrix due to a temporary arrest in nail matrix activity. Hand-foot-and-mouth disease (HFMD) is a relatively common viral infection, especially in children. Although the relationship between onychomadesis and HFMD has been noted, there are few reports in the literature.^1-9 We present 2 cases of onychomadesis following HFMD in Taiwanese siblings.

A 3-year-old girl presented with proximal nail plate detachment from the proximal nail fold on the bilateral great toenails (Figure 1) and a transverse whole-thickness sulcus on the bilateral thumbnails (Figure 2) of several weeks’ duration. Her 6-year-old sister had similar nail changes. Hand-foot-and-mouth disease was diagnosed about 4 weeks prior to nail changes. The mother reported that only the younger sister experienced fever. There was no history of notable medication intake, nail trauma, periungual erythema, vesicular lesion, or dermatitis. In both patients, the nail changes were temporary with spontaneous normal nail plate regrowth several months later. A diagnosis of onychomadesis was made.

The etiology of onychomadesis includes drug ingestion, especially chemotherapy; severe systemic diseases; high fever; infection, including viral illnesses such as influenza, measles, and HFMD; and idiopathic onychomadesis.^1,2,5,10 In 2000, Clementz and Mancini¹ reported 5 children with nail matrix arrest following HFMD and suggested an epidemic caused by the same virus strain. Bernier et al² reported another 4 cases and suggested more than one viral strain may have been implicated in the nail matrix arrest. Although these authors list HFMD as one of the causes of onychomadesis,^1,2 the number of cases reported was small; however, studies with a larger number of cases and even outbreak have been reported more recently.^3-8 Salazar et al³ reported an onychomadesis outbreak associated with HFMD in Valencia, Spain, in 2008 (N=298). This outbreak primarily was caused by coxsackievirus (CV) A10 (49% of cases).⁵ Another onychomadesis outbreak occurred in Saragossa, Spain, in 2008, and CV B1, B2, and unidentified nonpoliovirus enterovirus were isolated.⁶ Outbreaks also occurred in Finland in 2008, and the causative agents were identified as CV A6 and A10.^7,8 The latency period for onychomadesis following HFMD was 1 to 2 months (mean, 40 days), and the majority of cases occurred in patients younger than 6 years.^1-5 Not all of the nails were involved; in one report, each patient shed only 4 nails on average.⁶

Although there is a definite relationship between HFMD and onychomadesis, the mechanism is still unclear. Some authors claim that nail matrix arrest is caused by high fever¹⁰; however, we found that 40% (2/5)¹ to 63% (10/16)⁴ of reported cases did not have a fever. Additionally, only 1 of our patients had fever. Therefore high fever–induced nail matrix arrest is not a reasonable explanation. Davia et al⁵ observed no relationship between onychomadesis and the severity of HFMD. In addition, no serious complications of HFMD were mentioned in prior reports.

We propose that HFMD-related onychomadesis is caused by the viral infection itself, rather than by severe systemic disease.^1-5,7 Certain viral strains associated with HFMD can induce arrest of nail matrix activity. Osterback et al⁷ detected CV A6 in shed nail fragments and suggested that virus replication damaged the nail matrix and resulted in temporary nail dystrophy. This hypothesis can explain that only some nails, not all, were involved. In our cases, we noted an incomplete and slanted cleft on the thumbnail (Figure 2). We also found that incomplete onychomadesis appeared in the clinical photograph from a prior report.⁵ The slanted cleft in our case may be caused by secondary external force after original incomplete onychomadesis or a different rate of nail regrowth because of different intensity of nail matrix damage. The phenomenon of incomplete onychomadesis in the same nail further suggests the mechanism of onychomadesis following HFMD is localized nail matrix damage.

In conclusion, we report 2 cases of onychomadesis associated with HFMD. Our report highlights that there is no racial difference in post-HFMD onychomadesis. These cases highlight that HFMD is an important cause of onychomadesis, especially in children. We suggest that certain viral strains associated with HFMD may specifically arrest nail matrix growth activity, regardless of fever or disease severity.

To the Editor:

Onychomadesis is characterized by separation of the nail plate from the matrix due to a temporary arrest in nail matrix activity. Hand-foot-and-mouth disease (HFMD) is a relatively common viral infection, especially in children. Although the relationship between onychomadesis and HFMD has been noted, there are few reports in the literature.^1-9 We present 2 cases of onychomadesis following HFMD in Taiwanese siblings.

A 3-year-old girl presented with proximal nail plate detachment from the proximal nail fold on the bilateral great toenails (Figure 1) and a transverse whole-thickness sulcus on the bilateral thumbnails (Figure 2) of several weeks’ duration. Her 6-year-old sister had similar nail changes. Hand-foot-and-mouth disease was diagnosed about 4 weeks prior to nail changes. The mother reported that only the younger sister experienced fever. There was no history of notable medication intake, nail trauma, periungual erythema, vesicular lesion, or dermatitis. In both patients, the nail changes were temporary with spontaneous normal nail plate regrowth several months later. A diagnosis of onychomadesis was made.

The etiology of onychomadesis includes drug ingestion, especially chemotherapy; severe systemic diseases; high fever; infection, including viral illnesses such as influenza, measles, and HFMD; and idiopathic onychomadesis.^1,2,5,10 In 2000, Clementz and Mancini¹ reported 5 children with nail matrix arrest following HFMD and suggested an epidemic caused by the same virus strain. Bernier et al² reported another 4 cases and suggested more than one viral strain may have been implicated in the nail matrix arrest. Although these authors list HFMD as one of the causes of onychomadesis,^1,2 the number of cases reported was small; however, studies with a larger number of cases and even outbreak have been reported more recently.^3-8 Salazar et al³ reported an onychomadesis outbreak associated with HFMD in Valencia, Spain, in 2008 (N=298). This outbreak primarily was caused by coxsackievirus (CV) A10 (49% of cases).⁵ Another onychomadesis outbreak occurred in Saragossa, Spain, in 2008, and CV B1, B2, and unidentified nonpoliovirus enterovirus were isolated.⁶ Outbreaks also occurred in Finland in 2008, and the causative agents were identified as CV A6 and A10.^7,8 The latency period for onychomadesis following HFMD was 1 to 2 months (mean, 40 days), and the majority of cases occurred in patients younger than 6 years.^1-5 Not all of the nails were involved; in one report, each patient shed only 4 nails on average.⁶

Although there is a definite relationship between HFMD and onychomadesis, the mechanism is still unclear. Some authors claim that nail matrix arrest is caused by high fever¹⁰; however, we found that 40% (2/5)¹ to 63% (10/16)⁴ of reported cases did not have a fever. Additionally, only 1 of our patients had fever. Therefore high fever–induced nail matrix arrest is not a reasonable explanation. Davia et al⁵ observed no relationship between onychomadesis and the severity of HFMD. In addition, no serious complications of HFMD were mentioned in prior reports.

We propose that HFMD-related onychomadesis is caused by the viral infection itself, rather than by severe systemic disease.^1-5,7 Certain viral strains associated with HFMD can induce arrest of nail matrix activity. Osterback et al⁷ detected CV A6 in shed nail fragments and suggested that virus replication damaged the nail matrix and resulted in temporary nail dystrophy. This hypothesis can explain that only some nails, not all, were involved. In our cases, we noted an incomplete and slanted cleft on the thumbnail (Figure 2). We also found that incomplete onychomadesis appeared in the clinical photograph from a prior report.⁵ The slanted cleft in our case may be caused by secondary external force after original incomplete onychomadesis or a different rate of nail regrowth because of different intensity of nail matrix damage. The phenomenon of incomplete onychomadesis in the same nail further suggests the mechanism of onychomadesis following HFMD is localized nail matrix damage.

In conclusion, we report 2 cases of onychomadesis associated with HFMD. Our report highlights that there is no racial difference in post-HFMD onychomadesis. These cases highlight that HFMD is an important cause of onychomadesis, especially in children. We suggest that certain viral strains associated with HFMD may specifically arrest nail matrix growth activity, regardless of fever or disease severity.

To the Editor:

Onychomadesis is characterized by separation of the nail plate from the matrix due to a temporary arrest in nail matrix activity. Hand-foot-and-mouth disease (HFMD) is a relatively common viral infection, especially in children. Although the relationship between onychomadesis and HFMD has been noted, there are few reports in the literature.^1-9 We present 2 cases of onychomadesis following HFMD in Taiwanese siblings.

A 3-year-old girl presented with proximal nail plate detachment from the proximal nail fold on the bilateral great toenails (Figure 1) and a transverse whole-thickness sulcus on the bilateral thumbnails (Figure 2) of several weeks’ duration. Her 6-year-old sister had similar nail changes. Hand-foot-and-mouth disease was diagnosed about 4 weeks prior to nail changes. The mother reported that only the younger sister experienced fever. There was no history of notable medication intake, nail trauma, periungual erythema, vesicular lesion, or dermatitis. In both patients, the nail changes were temporary with spontaneous normal nail plate regrowth several months later. A diagnosis of onychomadesis was made.

The etiology of onychomadesis includes drug ingestion, especially chemotherapy; severe systemic diseases; high fever; infection, including viral illnesses such as influenza, measles, and HFMD; and idiopathic onychomadesis.^1,2,5,10 In 2000, Clementz and Mancini¹ reported 5 children with nail matrix arrest following HFMD and suggested an epidemic caused by the same virus strain. Bernier et al² reported another 4 cases and suggested more than one viral strain may have been implicated in the nail matrix arrest. Although these authors list HFMD as one of the causes of onychomadesis,^1,2 the number of cases reported was small; however, studies with a larger number of cases and even outbreak have been reported more recently.^3-8 Salazar et al³ reported an onychomadesis outbreak associated with HFMD in Valencia, Spain, in 2008 (N=298). This outbreak primarily was caused by coxsackievirus (CV) A10 (49% of cases).⁵ Another onychomadesis outbreak occurred in Saragossa, Spain, in 2008, and CV B1, B2, and unidentified nonpoliovirus enterovirus were isolated.⁶ Outbreaks also occurred in Finland in 2008, and the causative agents were identified as CV A6 and A10.^7,8 The latency period for onychomadesis following HFMD was 1 to 2 months (mean, 40 days), and the majority of cases occurred in patients younger than 6 years.^1-5 Not all of the nails were involved; in one report, each patient shed only 4 nails on average.⁶

Although there is a definite relationship between HFMD and onychomadesis, the mechanism is still unclear. Some authors claim that nail matrix arrest is caused by high fever¹⁰; however, we found that 40% (2/5)¹ to 63% (10/16)⁴ of reported cases did not have a fever. Additionally, only 1 of our patients had fever. Therefore high fever–induced nail matrix arrest is not a reasonable explanation. Davia et al⁵ observed no relationship between onychomadesis and the severity of HFMD. In addition, no serious complications of HFMD were mentioned in prior reports.

We propose that HFMD-related onychomadesis is caused by the viral infection itself, rather than by severe systemic disease.^1-5,7 Certain viral strains associated with HFMD can induce arrest of nail matrix activity. Osterback et al⁷ detected CV A6 in shed nail fragments and suggested that virus replication damaged the nail matrix and resulted in temporary nail dystrophy. This hypothesis can explain that only some nails, not all, were involved. In our cases, we noted an incomplete and slanted cleft on the thumbnail (Figure 2). We also found that incomplete onychomadesis appeared in the clinical photograph from a prior report.⁵ The slanted cleft in our case may be caused by secondary external force after original incomplete onychomadesis or a different rate of nail regrowth because of different intensity of nail matrix damage. The phenomenon of incomplete onychomadesis in the same nail further suggests the mechanism of onychomadesis following HFMD is localized nail matrix damage.

In conclusion, we report 2 cases of onychomadesis associated with HFMD. Our report highlights that there is no racial difference in post-HFMD onychomadesis. These cases highlight that HFMD is an important cause of onychomadesis, especially in children. We suggest that certain viral strains associated with HFMD may specifically arrest nail matrix growth activity, regardless of fever or disease severity.