It is customary at the end of the year for editors of journals and magazines to publish “the best and the worst of the year” or top 10 lists of events or articles of the year, or even the “most important” discoveries or people of the year. Some publications survey their readers; others invite experts to opine on the selection. What is nearly always missing from these newsworthy roundups are the criteria for determining what meets the mark. But this is a crucial piece of missing information, and without it, many of these rankings have little worth.

Words like important, best, and worst are not factual claims but value judgments. For a value judgment to have validity, there must be a substantive basis for making the determination. Put less ponderously, readers need to understand what makes a person, action, or decision valuable or important.

Being a medical ethicist, I tend to think in terms of good and bad, right and wrong—hence, the title of this editorial. But even these essential terms of evaluation in our language must have a frame of reference or at least a description to have meaning when applied, especially if the terms are to be compared. For moral philosophy, the parent of medical ethics, these frames or bases for making judgments about the rightness or wrongness of conduct are often found in ethical theories.

Three of the most recognized and significant ethical theories are consequentialist, deontology, and virtue ethics. It is important to understand these theories to grasp how I decided on my list of the right and wrong of 2017. However due to space limitations, I will only provide a nutshell summary of these theories. Readers interested in cracking the nut wider may want to consult the references on ethical theory at the end of the essay.¹

Consequentialist theories—utilitarianism being the most well known in health care—argue that what makes an action right or good is what brings about the most happiness for the most people. What is determinative of rightness is the outcome.

In direct opposition to consequentialism is deontology. The consequences do not matter at all to the deontologist, right and good have to do with intent, and the only truly right intent is acting for the sake of duty alone.

Virtue ethics finds the core of right and good in the character of the virtuous person. Right actions and good intent each spring from the root of an individual of moral excellence.²

Establishing these ethical theories as the criteria for judgment, I now turn to my choice for the right and the good, the “best” of federal practice in 2017. (Next month my editorial will focus on the bad or the “worst” of 2017 federal health care.) Upfront, I acknowledge these choices are subjective, but I justify them by using the theories set forth. We welcome readers to send us their selections.

The Best

While journalists and politicians have widely criticized the White House response (or lack thereof) to the destructive storms that occurred during this hurricane season, little attention has been paid to the response of the 3 federal health care agencies, which was quick, dedicated, and caring. And it is this response that makes it my best of 2017. The vulnerability of areas from Houston to Puerto Rico, some of which still lack the basic services of civilization, are struggling with loss of life and hope, powerless to protect what is left in the wake of the storms, only amplifies the desperate need for the human and material resources that the DoD, VA, and PHS have committed.

Testifying before the Senate Homeland Security and Governmental Affairs Committee, Robert G. Salesses, deputy assistant secretary of defense, chronicled the outpouring of DoD aid. “Military units cleared critical roadways, transported life-sustaining commodities, provided fuel distribution, conducted assessments of civilian hospitals, and provided medical support to include evacuating patients back to the continental United States.”³

The VA Disaster Emergency Medical Personnel system also went into high gear. In my facility and in many others, there were so many volunteers that facility leaders had to balance their clinical needs with the selfless desire to help the veterans and fellow federal practitioners who were in harm’s way.

According to Susan Wentzell, VISN 8 deputy communication manager and content manager:

“Despite the destruction caused by these monster storms, Veterans continued to receive vital health care and other support, thanks to the selfless efforts of thousands of dedicated VA employees who rallied together to provide around-the-clock care for patients sheltered-in-place in the eight large, hurricane-constructed VA hospitals and to get services back up and running in dozens of outpatient clinics impacted in the Southeast corridor of the U.S. and the Caribbean.”⁴

When Hurricane Maria ravaged Puerto Rico, medical personnel from the VA and the PHS Commissioned Corps staffed Federal Medical Stations in Manati and Bayamon, Puerto Rico, which provided cared for up to 250 people at a time. The officers of the Commissioned Corps also helped support the civilian health care infrastructure.

From a utilitarian perspective, the benefit of these relief efforts is obvious. They were literally life-saving and health preserving for the thousands who were injured in the wreckage of wind and rain, ill from the collapse of public services, as well as those psychologically traumatized. And had these men and women of the VA, PHS, and DoD not come to the aid of the victims of these unprecedented national disasters, the toll of human suffering and bereavement would have been far worse.

Deontologically, each of these government employees did their duty; many volunteered, and even those who were ordered to assist did so with a compassion and dedication that went far beyond doing a job. None of the historic drives of humankind to place themselves in harm’s way—power, money, or fame—motivated those who answered the call; only a duty to serve and an intention to help.

Each person who left the security of home and the comfort of friends and family displayed the highest qualities of virtue ethics: altruism, professionalism, empathy, and integrity among other virtues.

In preparing for this column, I read stories of health care practitioners and nonclinical staff who not only reached out, but also reached beyond any expectation, clearly demonstrating outstanding professionalism and humanism.

I end with just one of these inspirational accounts. As Hurricane Irma approached the Florida coast, veteran employee Tim Myers braved the coming storm to get to work. That is far harder and braver than it seems, because Myers, who is a pharmacy technician and delivers medications to inpatients at the James A. Haley VA, is a quadriplegic in a wheelchair. The humility of his laconic description of his supererogatory conduct is equally impressive. “I appreciate that, but it really wasn’t that big of a deal to me,” Myers said.  “I mean, I had to get here.”⁵

It is customary at the end of the year for editors of journals and magazines to publish “the best and the worst of the year” or top 10 lists of events or articles of the year, or even the “most important” discoveries or people of the year. Some publications survey their readers; others invite experts to opine on the selection. What is nearly always missing from these newsworthy roundups are the criteria for determining what meets the mark. But this is a crucial piece of missing information, and without it, many of these rankings have little worth.

Words like important, best, and worst are not factual claims but value judgments. For a value judgment to have validity, there must be a substantive basis for making the determination. Put less ponderously, readers need to understand what makes a person, action, or decision valuable or important.

Being a medical ethicist, I tend to think in terms of good and bad, right and wrong—hence, the title of this editorial. But even these essential terms of evaluation in our language must have a frame of reference or at least a description to have meaning when applied, especially if the terms are to be compared. For moral philosophy, the parent of medical ethics, these frames or bases for making judgments about the rightness or wrongness of conduct are often found in ethical theories.

Three of the most recognized and significant ethical theories are consequentialist, deontology, and virtue ethics. It is important to understand these theories to grasp how I decided on my list of the right and wrong of 2017. However due to space limitations, I will only provide a nutshell summary of these theories. Readers interested in cracking the nut wider may want to consult the references on ethical theory at the end of the essay.¹

Consequentialist theories—utilitarianism being the most well known in health care—argue that what makes an action right or good is what brings about the most happiness for the most people. What is determinative of rightness is the outcome.

In direct opposition to consequentialism is deontology. The consequences do not matter at all to the deontologist, right and good have to do with intent, and the only truly right intent is acting for the sake of duty alone.

Virtue ethics finds the core of right and good in the character of the virtuous person. Right actions and good intent each spring from the root of an individual of moral excellence.²

Establishing these ethical theories as the criteria for judgment, I now turn to my choice for the right and the good, the “best” of federal practice in 2017. (Next month my editorial will focus on the bad or the “worst” of 2017 federal health care.) Upfront, I acknowledge these choices are subjective, but I justify them by using the theories set forth. We welcome readers to send us their selections.

The Best

While journalists and politicians have widely criticized the White House response (or lack thereof) to the destructive storms that occurred during this hurricane season, little attention has been paid to the response of the 3 federal health care agencies, which was quick, dedicated, and caring. And it is this response that makes it my best of 2017. The vulnerability of areas from Houston to Puerto Rico, some of which still lack the basic services of civilization, are struggling with loss of life and hope, powerless to protect what is left in the wake of the storms, only amplifies the desperate need for the human and material resources that the DoD, VA, and PHS have committed.

Testifying before the Senate Homeland Security and Governmental Affairs Committee, Robert G. Salesses, deputy assistant secretary of defense, chronicled the outpouring of DoD aid. “Military units cleared critical roadways, transported life-sustaining commodities, provided fuel distribution, conducted assessments of civilian hospitals, and provided medical support to include evacuating patients back to the continental United States.”³

The VA Disaster Emergency Medical Personnel system also went into high gear. In my facility and in many others, there were so many volunteers that facility leaders had to balance their clinical needs with the selfless desire to help the veterans and fellow federal practitioners who were in harm’s way.

According to Susan Wentzell, VISN 8 deputy communication manager and content manager:

“Despite the destruction caused by these monster storms, Veterans continued to receive vital health care and other support, thanks to the selfless efforts of thousands of dedicated VA employees who rallied together to provide around-the-clock care for patients sheltered-in-place in the eight large, hurricane-constructed VA hospitals and to get services back up and running in dozens of outpatient clinics impacted in the Southeast corridor of the U.S. and the Caribbean.”⁴

When Hurricane Maria ravaged Puerto Rico, medical personnel from the VA and the PHS Commissioned Corps staffed Federal Medical Stations in Manati and Bayamon, Puerto Rico, which provided cared for up to 250 people at a time. The officers of the Commissioned Corps also helped support the civilian health care infrastructure.

From a utilitarian perspective, the benefit of these relief efforts is obvious. They were literally life-saving and health preserving for the thousands who were injured in the wreckage of wind and rain, ill from the collapse of public services, as well as those psychologically traumatized. And had these men and women of the VA, PHS, and DoD not come to the aid of the victims of these unprecedented national disasters, the toll of human suffering and bereavement would have been far worse.

Deontologically, each of these government employees did their duty; many volunteered, and even those who were ordered to assist did so with a compassion and dedication that went far beyond doing a job. None of the historic drives of humankind to place themselves in harm’s way—power, money, or fame—motivated those who answered the call; only a duty to serve and an intention to help.

Each person who left the security of home and the comfort of friends and family displayed the highest qualities of virtue ethics: altruism, professionalism, empathy, and integrity among other virtues.

In preparing for this column, I read stories of health care practitioners and nonclinical staff who not only reached out, but also reached beyond any expectation, clearly demonstrating outstanding professionalism and humanism.

I end with just one of these inspirational accounts. As Hurricane Irma approached the Florida coast, veteran employee Tim Myers braved the coming storm to get to work. That is far harder and braver than it seems, because Myers, who is a pharmacy technician and delivers medications to inpatients at the James A. Haley VA, is a quadriplegic in a wheelchair. The humility of his laconic description of his supererogatory conduct is equally impressive. “I appreciate that, but it really wasn’t that big of a deal to me,” Myers said.  “I mean, I had to get here.”⁵

It is customary at the end of the year for editors of journals and magazines to publish “the best and the worst of the year” or top 10 lists of events or articles of the year, or even the “most important” discoveries or people of the year. Some publications survey their readers; others invite experts to opine on the selection. What is nearly always missing from these newsworthy roundups are the criteria for determining what meets the mark. But this is a crucial piece of missing information, and without it, many of these rankings have little worth.

Words like important, best, and worst are not factual claims but value judgments. For a value judgment to have validity, there must be a substantive basis for making the determination. Put less ponderously, readers need to understand what makes a person, action, or decision valuable or important.

Being a medical ethicist, I tend to think in terms of good and bad, right and wrong—hence, the title of this editorial. But even these essential terms of evaluation in our language must have a frame of reference or at least a description to have meaning when applied, especially if the terms are to be compared. For moral philosophy, the parent of medical ethics, these frames or bases for making judgments about the rightness or wrongness of conduct are often found in ethical theories.

Three of the most recognized and significant ethical theories are consequentialist, deontology, and virtue ethics. It is important to understand these theories to grasp how I decided on my list of the right and wrong of 2017. However due to space limitations, I will only provide a nutshell summary of these theories. Readers interested in cracking the nut wider may want to consult the references on ethical theory at the end of the essay.¹

Consequentialist theories—utilitarianism being the most well known in health care—argue that what makes an action right or good is what brings about the most happiness for the most people. What is determinative of rightness is the outcome.

In direct opposition to consequentialism is deontology. The consequences do not matter at all to the deontologist, right and good have to do with intent, and the only truly right intent is acting for the sake of duty alone.

Virtue ethics finds the core of right and good in the character of the virtuous person. Right actions and good intent each spring from the root of an individual of moral excellence.²

Establishing these ethical theories as the criteria for judgment, I now turn to my choice for the right and the good, the “best” of federal practice in 2017. (Next month my editorial will focus on the bad or the “worst” of 2017 federal health care.) Upfront, I acknowledge these choices are subjective, but I justify them by using the theories set forth. We welcome readers to send us their selections.

The Best

While journalists and politicians have widely criticized the White House response (or lack thereof) to the destructive storms that occurred during this hurricane season, little attention has been paid to the response of the 3 federal health care agencies, which was quick, dedicated, and caring. And it is this response that makes it my best of 2017. The vulnerability of areas from Houston to Puerto Rico, some of which still lack the basic services of civilization, are struggling with loss of life and hope, powerless to protect what is left in the wake of the storms, only amplifies the desperate need for the human and material resources that the DoD, VA, and PHS have committed.

Testifying before the Senate Homeland Security and Governmental Affairs Committee, Robert G. Salesses, deputy assistant secretary of defense, chronicled the outpouring of DoD aid. “Military units cleared critical roadways, transported life-sustaining commodities, provided fuel distribution, conducted assessments of civilian hospitals, and provided medical support to include evacuating patients back to the continental United States.”³

The VA Disaster Emergency Medical Personnel system also went into high gear. In my facility and in many others, there were so many volunteers that facility leaders had to balance their clinical needs with the selfless desire to help the veterans and fellow federal practitioners who were in harm’s way.

According to Susan Wentzell, VISN 8 deputy communication manager and content manager:

“Despite the destruction caused by these monster storms, Veterans continued to receive vital health care and other support, thanks to the selfless efforts of thousands of dedicated VA employees who rallied together to provide around-the-clock care for patients sheltered-in-place in the eight large, hurricane-constructed VA hospitals and to get services back up and running in dozens of outpatient clinics impacted in the Southeast corridor of the U.S. and the Caribbean.”⁴

When Hurricane Maria ravaged Puerto Rico, medical personnel from the VA and the PHS Commissioned Corps staffed Federal Medical Stations in Manati and Bayamon, Puerto Rico, which provided cared for up to 250 people at a time. The officers of the Commissioned Corps also helped support the civilian health care infrastructure.

From a utilitarian perspective, the benefit of these relief efforts is obvious. They were literally life-saving and health preserving for the thousands who were injured in the wreckage of wind and rain, ill from the collapse of public services, as well as those psychologically traumatized. And had these men and women of the VA, PHS, and DoD not come to the aid of the victims of these unprecedented national disasters, the toll of human suffering and bereavement would have been far worse.

Deontologically, each of these government employees did their duty; many volunteered, and even those who were ordered to assist did so with a compassion and dedication that went far beyond doing a job. None of the historic drives of humankind to place themselves in harm’s way—power, money, or fame—motivated those who answered the call; only a duty to serve and an intention to help.

Each person who left the security of home and the comfort of friends and family displayed the highest qualities of virtue ethics: altruism, professionalism, empathy, and integrity among other virtues.

In preparing for this column, I read stories of health care practitioners and nonclinical staff who not only reached out, but also reached beyond any expectation, clearly demonstrating outstanding professionalism and humanism.

I end with just one of these inspirational accounts. As Hurricane Irma approached the Florida coast, veteran employee Tim Myers braved the coming storm to get to work. That is far harder and braver than it seems, because Myers, who is a pharmacy technician and delivers medications to inpatients at the James A. Haley VA, is a quadriplegic in a wheelchair. The humility of his laconic description of his supererogatory conduct is equally impressive. “I appreciate that, but it really wasn’t that big of a deal to me,” Myers said.  “I mean, I had to get here.”⁵

Case Report

A 58-year-old man presented for evaluation of a pruritic rash involving the pubic area of 30 years’ duration. Multiple primary care physicians and dermatologists had evaluated the patient during this period, but he noted a specific diagnosis had not been rendered and multiple treatments had been unsuccessful. The patient described a rash, which was absent at the time of evaluation, as a self-remitting and exacerbating irritation typically induced by sweating and physical activity. The patient also stated that the irritation was associated with a strong, distinct, musty odor that severely interrupted his sex life and decreased his quality of life. Prior treatments included various topical corticosteroids, topical and oral antibiotics, and various homeopathic treatments that were minimally efficacious or nonefficacious. He was unsure if antifungals had previously been prescribed.

The patient’s medical history was notable for pulmonary interstitial fibrosis, anxiety, posttraumatic stress disorder, and mild glucose intolerance. The patient had no pertinent surgical history and no known drug allergies. Current medications included a bronchodilating inhaler, escitalopram, trazodone, buspirone, clonazepam, prazosin, gabapentin, and azithromycin for current upper respiratory tract infection. The patient was a former smoker and a social drinker.

On physical evaluation the pubic area displayed slight patchy erythema without a papular component and was otherwise unremarkable to the unaided eye. Upon palpation of the skin, there were no remarkable findings. Under dermoscopic evaluation, small white-yellow concretions along the hair shaft were noticed. Evaluation with a Wood lamp is shown in Figure 1.

The patient was treated empirically with ketoconazole cream 2% applied to the affected area once daily until follow-up 3 weeks later. The patient also was advised to shave the pubic area to remove potentially infected hairs, as white piedra (WP) was suspected. A diagnosis of WP was confirmed on histologic evaluation of pubic hair samples approximately 1 to 2 weeks later (Figure 2).

At 3-week follow-up, Wood lamp evaluation did not identify concretions along the pubic hair shafts. The patient was symptom free and extremely pleased. Of note, the patient did not shave the pubic area and was counseled on recurrence.

Comment

Piedra (meaning stone in Spanish) describes a group of fungal infections that present with gritty concretions on the hair shaft.^1,2 In 1911, Horta³ classified piedra into 2 subtypes: black piedra, caused by Piedraia hortae, and WP, caused by Trichosporon species. Black piedra occurs more frequently in tropical countries and commonly affects hair shafts on the scalp.⁴ White piedra most commonly affects the pubic area, with rare cases in scalp and facial hair.^1,5-7

Epidemiology
White piedra is seen worldwide, including Europe, South America, India, Southeast Asia, Africa, South America, and southern parts of the United States. The majority of cases occur in tropical and temperate regions.¹ White piedra likely is underdiagnosed; for example, in a study of 166 young men with genital concerns in Houston, Texas, Trichosporon was isolated in 40% of cultured scrotal hairs.⁸

Species Identification
There are several species of WP; special techniques must be used to differentiate them, which is beyond the scope of this case. The known species include Trichosporon asahii, Trichosporon asteroides, Trichosporon cutaneum, Trichosporon inkin, Trichosporon mucoides, and Trichosporon ovoides.¹Trichosporon asahii and T mucoides have been known to cause systemic infections in immunocompromised hosts known as trichosporonosis.^1,9 As an example of a special technique used for species recognition, Sugita et al¹⁰ used sequence analysis of the ribosomal DNA intergenic spacer 1 regions to distinguish T asahii isolates. Identification of species may be warranted in the proper clinical scenario; however, histologic evaluation by an experienced dermatopathologist frequently is sufficient to identify the Trichosporon genus.

Transmission
The 2 most common causative organisms of WP are T inkin and T ovoides. Furthermore, T inkin causes the vast majority of WP in the pubic region.⁸Trichosporon species may be found in air, soil, water, and sewage,⁷ and have been isolated in hair samples from horses, dogs, and monkeys.¹¹ The mode of transmission in humans remains elusive but has been reported from poor personal hygiene and bathing in stagnant water as well as sexual transmission in the case of pubic infestation.^5,8,11-13

Diagnosis and Differential
White piedra is characterized by the presence of adherent tan to white nodules along the hair shafts. The concretions tend to be softer than black piedra and, unlike trichomycosis, normally do not fluoresce.¹ They do not encircle the hair shaft as hair casts do and can be readily distinguished from Trichomycosis axillaris, black piedra, pediculosis, and trichorrhexis nodosa on microscopic examination.¹⁴ The hair shaft concretions of WP are difficult to visualize with the unaided eye. As a result, it is easily misdiagnosed.¹⁵ Upon palpation of the infected hair shafts, a grainy sensation is evident. Dermoscopy improves visualization, and fluorescence was useful in our case. Microscopic evaluation will identify the adherent organism and is readily cultured on Sabouraud agar.¹⁶ Although Trichosporon species typically do not fluoresce,¹ Wood lamp examination occasionally may reveal the organism, such as in our case. A possible explanation for this finding is the synergistic relationship with Corynebacterium,¹⁷ some producing fluorescent chemicals. Growth of Trichosporon species may be enhanced by or even dependent on Corynebacterium; therefore, WP is likely a coinfection of fungus and bacteria.^17,18 Studies also name a novel species of Brevibacterium in relationship with genital WP.¹⁹ This species was described as producing a foul odor, as in our patient.

Treatment
The American Academy of Dermatology’s Guidelines Committee recommends complete removal of the infected hairs.¹ The recommendation traditionally is hair removal in conjunction with topical or oral medications,¹ such as topical imidazoles, ciclopirox olamine, selenium sulfide 2%, chlorhexidine solution, zinc pyrithione, amphotericin B lotion, and oral itraconazole. Recurrence rates are high and spontaneous remission sometimes occurs.^9,20 Triazole antifungals currently are preferred for treatment of Trichosporon infections.⁵ Patients should be counseled to dispose of undergarments, as the organism has been recovered from cotton fibers and are a source of reinfection.^1,21

Conclusion

White piedra, though relatively uncommon, is likely underdiagnosed in the United States and should be suspected in any patient presenting with irritation and a foul odor in the genital area or multiple failed therapies for a nonspecific genital dermatitis. This clinical scenario warrants dermoscopic and Wood lamp examination of the affected skin and hair shafts in addition to microscopic examination of pubic hair shafts by a dermatopathologist. Fluorescence under Wood lamp may aid in diagnosis, and conflicting findings may be attributed to its synergistic relationship with Corynebacterium and Brevibacterium coinfection. Proper treatment includes shaving of the affected hair, oral or topical antifungal treatment, and disposal of affected clothing.

Case Report

A 58-year-old man presented for evaluation of a pruritic rash involving the pubic area of 30 years’ duration. Multiple primary care physicians and dermatologists had evaluated the patient during this period, but he noted a specific diagnosis had not been rendered and multiple treatments had been unsuccessful. The patient described a rash, which was absent at the time of evaluation, as a self-remitting and exacerbating irritation typically induced by sweating and physical activity. The patient also stated that the irritation was associated with a strong, distinct, musty odor that severely interrupted his sex life and decreased his quality of life. Prior treatments included various topical corticosteroids, topical and oral antibiotics, and various homeopathic treatments that were minimally efficacious or nonefficacious. He was unsure if antifungals had previously been prescribed.

The patient’s medical history was notable for pulmonary interstitial fibrosis, anxiety, posttraumatic stress disorder, and mild glucose intolerance. The patient had no pertinent surgical history and no known drug allergies. Current medications included a bronchodilating inhaler, escitalopram, trazodone, buspirone, clonazepam, prazosin, gabapentin, and azithromycin for current upper respiratory tract infection. The patient was a former smoker and a social drinker.

On physical evaluation the pubic area displayed slight patchy erythema without a papular component and was otherwise unremarkable to the unaided eye. Upon palpation of the skin, there were no remarkable findings. Under dermoscopic evaluation, small white-yellow concretions along the hair shaft were noticed. Evaluation with a Wood lamp is shown in Figure 1.

The patient was treated empirically with ketoconazole cream 2% applied to the affected area once daily until follow-up 3 weeks later. The patient also was advised to shave the pubic area to remove potentially infected hairs, as white piedra (WP) was suspected. A diagnosis of WP was confirmed on histologic evaluation of pubic hair samples approximately 1 to 2 weeks later (Figure 2).

At 3-week follow-up, Wood lamp evaluation did not identify concretions along the pubic hair shafts. The patient was symptom free and extremely pleased. Of note, the patient did not shave the pubic area and was counseled on recurrence.

Comment

Piedra (meaning stone in Spanish) describes a group of fungal infections that present with gritty concretions on the hair shaft.^1,2 In 1911, Horta³ classified piedra into 2 subtypes: black piedra, caused by Piedraia hortae, and WP, caused by Trichosporon species. Black piedra occurs more frequently in tropical countries and commonly affects hair shafts on the scalp.⁴ White piedra most commonly affects the pubic area, with rare cases in scalp and facial hair.^1,5-7

Epidemiology
White piedra is seen worldwide, including Europe, South America, India, Southeast Asia, Africa, South America, and southern parts of the United States. The majority of cases occur in tropical and temperate regions.¹ White piedra likely is underdiagnosed; for example, in a study of 166 young men with genital concerns in Houston, Texas, Trichosporon was isolated in 40% of cultured scrotal hairs.⁸

Species Identification
There are several species of WP; special techniques must be used to differentiate them, which is beyond the scope of this case. The known species include Trichosporon asahii, Trichosporon asteroides, Trichosporon cutaneum, Trichosporon inkin, Trichosporon mucoides, and Trichosporon ovoides.¹Trichosporon asahii and T mucoides have been known to cause systemic infections in immunocompromised hosts known as trichosporonosis.^1,9 As an example of a special technique used for species recognition, Sugita et al¹⁰ used sequence analysis of the ribosomal DNA intergenic spacer 1 regions to distinguish T asahii isolates. Identification of species may be warranted in the proper clinical scenario; however, histologic evaluation by an experienced dermatopathologist frequently is sufficient to identify the Trichosporon genus.

Transmission
The 2 most common causative organisms of WP are T inkin and T ovoides. Furthermore, T inkin causes the vast majority of WP in the pubic region.⁸Trichosporon species may be found in air, soil, water, and sewage,⁷ and have been isolated in hair samples from horses, dogs, and monkeys.¹¹ The mode of transmission in humans remains elusive but has been reported from poor personal hygiene and bathing in stagnant water as well as sexual transmission in the case of pubic infestation.^5,8,11-13

Diagnosis and Differential
White piedra is characterized by the presence of adherent tan to white nodules along the hair shafts. The concretions tend to be softer than black piedra and, unlike trichomycosis, normally do not fluoresce.¹ They do not encircle the hair shaft as hair casts do and can be readily distinguished from Trichomycosis axillaris, black piedra, pediculosis, and trichorrhexis nodosa on microscopic examination.¹⁴ The hair shaft concretions of WP are difficult to visualize with the unaided eye. As a result, it is easily misdiagnosed.¹⁵ Upon palpation of the infected hair shafts, a grainy sensation is evident. Dermoscopy improves visualization, and fluorescence was useful in our case. Microscopic evaluation will identify the adherent organism and is readily cultured on Sabouraud agar.¹⁶ Although Trichosporon species typically do not fluoresce,¹ Wood lamp examination occasionally may reveal the organism, such as in our case. A possible explanation for this finding is the synergistic relationship with Corynebacterium,¹⁷ some producing fluorescent chemicals. Growth of Trichosporon species may be enhanced by or even dependent on Corynebacterium; therefore, WP is likely a coinfection of fungus and bacteria.^17,18 Studies also name a novel species of Brevibacterium in relationship with genital WP.¹⁹ This species was described as producing a foul odor, as in our patient.

Treatment
The American Academy of Dermatology’s Guidelines Committee recommends complete removal of the infected hairs.¹ The recommendation traditionally is hair removal in conjunction with topical or oral medications,¹ such as topical imidazoles, ciclopirox olamine, selenium sulfide 2%, chlorhexidine solution, zinc pyrithione, amphotericin B lotion, and oral itraconazole. Recurrence rates are high and spontaneous remission sometimes occurs.^9,20 Triazole antifungals currently are preferred for treatment of Trichosporon infections.⁵ Patients should be counseled to dispose of undergarments, as the organism has been recovered from cotton fibers and are a source of reinfection.^1,21

Conclusion

White piedra, though relatively uncommon, is likely underdiagnosed in the United States and should be suspected in any patient presenting with irritation and a foul odor in the genital area or multiple failed therapies for a nonspecific genital dermatitis. This clinical scenario warrants dermoscopic and Wood lamp examination of the affected skin and hair shafts in addition to microscopic examination of pubic hair shafts by a dermatopathologist. Fluorescence under Wood lamp may aid in diagnosis, and conflicting findings may be attributed to its synergistic relationship with Corynebacterium and Brevibacterium coinfection. Proper treatment includes shaving of the affected hair, oral or topical antifungal treatment, and disposal of affected clothing.

Case Report

A 58-year-old man presented for evaluation of a pruritic rash involving the pubic area of 30 years’ duration. Multiple primary care physicians and dermatologists had evaluated the patient during this period, but he noted a specific diagnosis had not been rendered and multiple treatments had been unsuccessful. The patient described a rash, which was absent at the time of evaluation, as a self-remitting and exacerbating irritation typically induced by sweating and physical activity. The patient also stated that the irritation was associated with a strong, distinct, musty odor that severely interrupted his sex life and decreased his quality of life. Prior treatments included various topical corticosteroids, topical and oral antibiotics, and various homeopathic treatments that were minimally efficacious or nonefficacious. He was unsure if antifungals had previously been prescribed.

The patient’s medical history was notable for pulmonary interstitial fibrosis, anxiety, posttraumatic stress disorder, and mild glucose intolerance. The patient had no pertinent surgical history and no known drug allergies. Current medications included a bronchodilating inhaler, escitalopram, trazodone, buspirone, clonazepam, prazosin, gabapentin, and azithromycin for current upper respiratory tract infection. The patient was a former smoker and a social drinker.

On physical evaluation the pubic area displayed slight patchy erythema without a papular component and was otherwise unremarkable to the unaided eye. Upon palpation of the skin, there were no remarkable findings. Under dermoscopic evaluation, small white-yellow concretions along the hair shaft were noticed. Evaluation with a Wood lamp is shown in Figure 1.

The patient was treated empirically with ketoconazole cream 2% applied to the affected area once daily until follow-up 3 weeks later. The patient also was advised to shave the pubic area to remove potentially infected hairs, as white piedra (WP) was suspected. A diagnosis of WP was confirmed on histologic evaluation of pubic hair samples approximately 1 to 2 weeks later (Figure 2).

At 3-week follow-up, Wood lamp evaluation did not identify concretions along the pubic hair shafts. The patient was symptom free and extremely pleased. Of note, the patient did not shave the pubic area and was counseled on recurrence.

Comment

Piedra (meaning stone in Spanish) describes a group of fungal infections that present with gritty concretions on the hair shaft.^1,2 In 1911, Horta³ classified piedra into 2 subtypes: black piedra, caused by Piedraia hortae, and WP, caused by Trichosporon species. Black piedra occurs more frequently in tropical countries and commonly affects hair shafts on the scalp.⁴ White piedra most commonly affects the pubic area, with rare cases in scalp and facial hair.^1,5-7

Epidemiology
White piedra is seen worldwide, including Europe, South America, India, Southeast Asia, Africa, South America, and southern parts of the United States. The majority of cases occur in tropical and temperate regions.¹ White piedra likely is underdiagnosed; for example, in a study of 166 young men with genital concerns in Houston, Texas, Trichosporon was isolated in 40% of cultured scrotal hairs.⁸

Species Identification
There are several species of WP; special techniques must be used to differentiate them, which is beyond the scope of this case. The known species include Trichosporon asahii, Trichosporon asteroides, Trichosporon cutaneum, Trichosporon inkin, Trichosporon mucoides, and Trichosporon ovoides.¹Trichosporon asahii and T mucoides have been known to cause systemic infections in immunocompromised hosts known as trichosporonosis.^1,9 As an example of a special technique used for species recognition, Sugita et al¹⁰ used sequence analysis of the ribosomal DNA intergenic spacer 1 regions to distinguish T asahii isolates. Identification of species may be warranted in the proper clinical scenario; however, histologic evaluation by an experienced dermatopathologist frequently is sufficient to identify the Trichosporon genus.

Transmission
The 2 most common causative organisms of WP are T inkin and T ovoides. Furthermore, T inkin causes the vast majority of WP in the pubic region.⁸Trichosporon species may be found in air, soil, water, and sewage,⁷ and have been isolated in hair samples from horses, dogs, and monkeys.¹¹ The mode of transmission in humans remains elusive but has been reported from poor personal hygiene and bathing in stagnant water as well as sexual transmission in the case of pubic infestation.^5,8,11-13

Diagnosis and Differential
White piedra is characterized by the presence of adherent tan to white nodules along the hair shafts. The concretions tend to be softer than black piedra and, unlike trichomycosis, normally do not fluoresce.¹ They do not encircle the hair shaft as hair casts do and can be readily distinguished from Trichomycosis axillaris, black piedra, pediculosis, and trichorrhexis nodosa on microscopic examination.¹⁴ The hair shaft concretions of WP are difficult to visualize with the unaided eye. As a result, it is easily misdiagnosed.¹⁵ Upon palpation of the infected hair shafts, a grainy sensation is evident. Dermoscopy improves visualization, and fluorescence was useful in our case. Microscopic evaluation will identify the adherent organism and is readily cultured on Sabouraud agar.¹⁶ Although Trichosporon species typically do not fluoresce,¹ Wood lamp examination occasionally may reveal the organism, such as in our case. A possible explanation for this finding is the synergistic relationship with Corynebacterium,¹⁷ some producing fluorescent chemicals. Growth of Trichosporon species may be enhanced by or even dependent on Corynebacterium; therefore, WP is likely a coinfection of fungus and bacteria.^17,18 Studies also name a novel species of Brevibacterium in relationship with genital WP.¹⁹ This species was described as producing a foul odor, as in our patient.

Treatment
The American Academy of Dermatology’s Guidelines Committee recommends complete removal of the infected hairs.¹ The recommendation traditionally is hair removal in conjunction with topical or oral medications,¹ such as topical imidazoles, ciclopirox olamine, selenium sulfide 2%, chlorhexidine solution, zinc pyrithione, amphotericin B lotion, and oral itraconazole. Recurrence rates are high and spontaneous remission sometimes occurs.^9,20 Triazole antifungals currently are preferred for treatment of Trichosporon infections.⁵ Patients should be counseled to dispose of undergarments, as the organism has been recovered from cotton fibers and are a source of reinfection.^1,21

Conclusion

White piedra, though relatively uncommon, is likely underdiagnosed in the United States and should be suspected in any patient presenting with irritation and a foul odor in the genital area or multiple failed therapies for a nonspecific genital dermatitis. This clinical scenario warrants dermoscopic and Wood lamp examination of the affected skin and hair shafts in addition to microscopic examination of pubic hair shafts by a dermatopathologist. Fluorescence under Wood lamp may aid in diagnosis, and conflicting findings may be attributed to its synergistic relationship with Corynebacterium and Brevibacterium coinfection. Proper treatment includes shaving of the affected hair, oral or topical antifungal treatment, and disposal of affected clothing.

In 1960, Gorlin and Goltz¹ first described nevoid basal cell carcinoma syndrome (NBCCS) as a distinct clinical entity with multiple basal cell carcinomas (BCCs), jaw cysts, and bifid ribs. This rare autosomal-dominant genodermatosis has a minimal prevalence of 1 case per 57,000 individuals² and no sexual predilection.³ Nevoid basal cell carcinoma syndrome is caused by a mutation in the human homolog of a Drosophila gene, patched 1 (PTCH1), which is located on chromosome 9q22.^3.4,5 The major clinical diagnostic criteria includes multiple BCCs, odontogenic keratocysts, palmar or plantar pits, ectopic calcification of the falx cerebri, and a family history of NBCCS.⁶ Basal cell carcinoma formation is affected by both skin pigmentation and sun exposure; 80% of white patients with NBCCS will develop at least 1 BCC compared to only 40% of black patients with NBCCS.⁷ Goldstein et al⁸ postulated that this disparity is associated with increased skin pigmentation providing UV radiation protection, thus decreasing the tumor burden. We report a case of an 11-year-old black boy with NBCCS to highlight the treatment considerations in pediatric cases of NBCCS.

Case Report

An 11-year-old boy with Fitzpatrick skin type V presented with a history of multiple facial lesions after undergoing excision of large keratocysts from the right maxilla, left maxilla, and right mandible. Physical examination revealed multiple light to dark brown facial papules (Figure 1), palmar and plantar pitting (Figure 2), and frontal bossing.

He was previously diagnosed with autism and his surgical history was notable only for excision of the keratocysts. The patient was not taking any medications and did not have any drug allergies. There was no maternal family history of skin cancer or related syndromes; his paternal family history was unknown. A shave biopsy was performed on a facial papule from the right nasolabial fold. Histopathologic evaluation revealed findings consistent with a pigmented nodular BCC (Figure 3). The patient was subsequently sent for magnetic resonance imaging of the brain, which demonstrated calcifications along the tentorium. Genetic consultation confirmed a heterozygous mutation of the PTCH1 gene.

Over the next 12 months, the patient had multiple biopsy-proven pigmented BCCs. Initial management of these carcinomas located on cosmetically sensitive areas, including the upper eyelid and penis, were excised by a pediatric plastic surgeon. A truncal carcinoma was treated with electrodesiccation and curettage, which resulted in keloid formation. Early suspicious lesions were treated with imiquimod cream 5% 5 times weekly in combination with the prophylactic use of tretinoin cream 0.1%. Despite this treatment regimen, the patient continued to demonstrate multiple small clinical pigmented BCCs along the malar surfaces of the cheeks and dorsum of the nose. The patient’s mother deferred chemoprevention with an oral retinoid due to the extensive side-effect profile and long-term necessity of administration.

Management also encompassed BCC surveillance every 4 months; annual digital panorex of the jaw; routine dental screening; routine developmental screening; annual follow-up with a geneticist to ensure multidisciplinary care; and annual vision, hearing, and speech-screening examinations. Strict sun-protective measures were encouraged, including wearing a hat during physical education class.

Comment

Classification and Clinical Presentation
Nevoid basal cell carcinoma syndrome is a multisystem disorder that requires close monitoring under multidisciplinary care. Evans et al⁶ defined the diagnostic criteria of NBCCS to require the presence of 2 major criteria or 1 major and 2 minor criteria. The major criteria include multiple BCCs, an odontogenic keratocyst or polyostotic bone cyst, palmar or plantar pits, ectopic calcification of the falx cerebri, and family history of NBCCS. The minor criteria are defined as congenital skeletal anomalies; macrocephaly with frontal bossing; cardiac or ovarian fibromas; medulloblastoma; lymphomesenteric cysts; and congenital malformations such as cleft lip or palate, polydactyly, or eye anomalies.⁶ The mean age of initial BCC diagnosis is 21 years, with proliferation of cancers between puberty and 35 years of age.^7,9 Our case is unique due to the patient’s young age at the time of diagnosis as well as his presentation with multiple BCCs with a darker skin type. Kimonis et al⁷ reported that approximately 20% of black patients develop their first BCC by the age of 21 years and 40% by 35 years. The presence of multiple BCCs is complicated by the limited treatment options in a pediatric patient. The patient’s inability to withstand multiple procedures contributed to our clinical decision to have multiple lesions removed under general anesthesia by a pediatric plastic surgeon.

Due to the patient’s young age of onset, we placed a great emphasis on close surveillance and management. A management protocol for pediatric patients with NBCCS was described by Bree and Shah; BCNS Colloquium Group¹⁰ (eTable). We closely followed this protocol for surveillance; however, we scheduled dermatologic examinations every 4 months due to his extensive history of BCCs.

Management
Our case presents a challenging therapeutic and management dilemma. The management of NBCCS utilizes a multitude of treatment modalities, but many of them posed cosmetic challenges in our patient such as postinflammatory hypopigmentation and the propensity for keloid formation. Although surgical excision or Mohs micrographic surgery is the standard of treatment of nodular BCCs, we were limited due to the patient’s inability to tolerate multiple surgical procedures without the use of general anesthesia.

Case reports have discussed the use of CO₂ laser resurfacing for management of multiple facial BCCs in patients with NBCCS. Doctoroff et al¹¹ treated a patient with 45 facial BCCs with full-face CO₂ laser resurfacing, and in a 10-month follow-up period the patient developed 6 new BCCs on the face. Nouri et al¹² described 3 cases of multiple BCCs on the face, trunk, and extremities treated with ultrapulse CO₂ laser with postoperative Mohs sections verifying complete histologic clearance of tumors. All 3 patients had Fitzpatrick skin type IV; their ages were 2, 16, and 35 years. Local anesthesia was used in the 2-year-old patient and intravenous sedation in the 16-year-old patient.¹² Although CO₂ laser therapy may be a practical treatment option, it posed too many cosmetic concerns in our patient.

Photodynamic therapy (PDT) is an emerging treatment option for NBCCS patients. Itkin and Gilchrest¹³ treated 2 NBCCS patients with δ-aminolevulinic acid for 1 to 5 hours prior to treatment with blue light therapy. Complete clearance was documented in 89% (8/9) of superficial BCCs and 31% (5/16) of nodular BCCs on the face, indicating that blue light treatment may reduce the cutaneous tumor burden.¹³ Oseroff et al¹⁴ reported similar success in treating 3 children with NBCCS with 20% δ-aminolevulinic acid for 24 hours under occlusion followed by red light treatment. After 1 to 3 treatments, the children had 85% to 98% total clearance, demonstrating it as a viable treatment option in young patients that yields excellent cosmetic results and is well tolerated.¹⁴ Photodynamic therapy is reported to have a low risk of carcinogenicity¹⁵; however, there has been 1 reported case of melanoma developing at the site of multiple PDT treatments.¹⁶ Thus, the risk of carcinogenicity is increasingly bothersome in NBCCS patients due to their sensitivity to exposure. The limited number of studies using topical PDT on pediatric patients, the lack of treatment protocols for pediatric patients, and the need to use general anesthesia for pediatric patients all posed limitations to the use of PDT in our case.

Imiquimod cream 5% was shown in randomized, vehicle-controlled studies to be a safe and effective treatment of superficial BCCs when used 5 days weekly for 6 weeks.¹⁷ These studies excluded patients with NBCCS; however, other studies have been completed in patients with NBCCS. Kagy and Amonette¹⁸ successfully treated 3 nonfacial BCCs in a patient with NBCCS with imiquimod cream 5% daily for 18 weeks, with complete histologic resolution of the tumors. Micali et al¹⁹ also treated 4 patients with NBCCS using imiquimod cream 5% 3 to 5 times weekly for 8 to 14 weeks. Thirteen of 17 BCCs resolved, as confirmed with histologic evaluation.¹⁹ One case report revealed a child with NBCCS who was successfully managed with topical fluorouracil and topical tretinoin for more than 10 years.²⁰ Our patient used imiquimod cream 5% 5 times weekly, which inhibited the growth of existing lesions but did not clear them entirely, as they were nodular in nature.

Chemoprevention with oral retinoids breaches a controversial treatment topic. In 1989, a case study of an NBCCS patient treated with surgical excision and oral etretinate for 12 months documented reduction of large tumors.²¹ A multicenter clinical trial reported that low-dose isotretinoin (10 mg daily) is ineffective in preventing the occurrence of new BCC formation in patients with a history of 2 or more sporadic BCCs.²² Chemoprevention with oral retinoids is well known for being effective for squamous cell carcinomas and actinic keratosis; however, the treatment is less effective for BCCs.²² Most importantly, the extensive side-effect profile and toxicity associated with long-term administration of oral retinoids prohibits many practitioners from routinely using them in pediatric NBCCS patients.

Nevoid basal cell carcinoma syndrome patients are exquisitely sensitive to ionizing radiation and the effects of UV exposure. Therefore, it is essential to emphasize the importance of sun-protective measures such as sun avoidance, broad-spectrum sunscreen use, and sun-protective clothing.

Conclusion

Nevoid basal cell carcinoma syndrome is a multisystem disorder with a notable predisposition for skin cancer. Our case demonstrates the treatment considerations in a pediatric patient with Fitzpatrick skin type V. Pediatric NBCCS patients develop BCCs at a young age and will continue to develop additional lesions throughout life; therefore, skin preservation is an important consideration when choosing the appropriate treatment regimen. Particularly in our patient, utilizing multiple strategic treatment modalities in combination with chemoprevention moving forward will be a continued management challenge. Strict adherence to a surveillance protocol is encouraged to closely monitor the systemic manifestations of the disorder.

In 1960, Gorlin and Goltz¹ first described nevoid basal cell carcinoma syndrome (NBCCS) as a distinct clinical entity with multiple basal cell carcinomas (BCCs), jaw cysts, and bifid ribs. This rare autosomal-dominant genodermatosis has a minimal prevalence of 1 case per 57,000 individuals² and no sexual predilection.³ Nevoid basal cell carcinoma syndrome is caused by a mutation in the human homolog of a Drosophila gene, patched 1 (PTCH1), which is located on chromosome 9q22.^3.4,5 The major clinical diagnostic criteria includes multiple BCCs, odontogenic keratocysts, palmar or plantar pits, ectopic calcification of the falx cerebri, and a family history of NBCCS.⁶ Basal cell carcinoma formation is affected by both skin pigmentation and sun exposure; 80% of white patients with NBCCS will develop at least 1 BCC compared to only 40% of black patients with NBCCS.⁷ Goldstein et al⁸ postulated that this disparity is associated with increased skin pigmentation providing UV radiation protection, thus decreasing the tumor burden. We report a case of an 11-year-old black boy with NBCCS to highlight the treatment considerations in pediatric cases of NBCCS.

Case Report

An 11-year-old boy with Fitzpatrick skin type V presented with a history of multiple facial lesions after undergoing excision of large keratocysts from the right maxilla, left maxilla, and right mandible. Physical examination revealed multiple light to dark brown facial papules (Figure 1), palmar and plantar pitting (Figure 2), and frontal bossing.

He was previously diagnosed with autism and his surgical history was notable only for excision of the keratocysts. The patient was not taking any medications and did not have any drug allergies. There was no maternal family history of skin cancer or related syndromes; his paternal family history was unknown. A shave biopsy was performed on a facial papule from the right nasolabial fold. Histopathologic evaluation revealed findings consistent with a pigmented nodular BCC (Figure 3). The patient was subsequently sent for magnetic resonance imaging of the brain, which demonstrated calcifications along the tentorium. Genetic consultation confirmed a heterozygous mutation of the PTCH1 gene.

Over the next 12 months, the patient had multiple biopsy-proven pigmented BCCs. Initial management of these carcinomas located on cosmetically sensitive areas, including the upper eyelid and penis, were excised by a pediatric plastic surgeon. A truncal carcinoma was treated with electrodesiccation and curettage, which resulted in keloid formation. Early suspicious lesions were treated with imiquimod cream 5% 5 times weekly in combination with the prophylactic use of tretinoin cream 0.1%. Despite this treatment regimen, the patient continued to demonstrate multiple small clinical pigmented BCCs along the malar surfaces of the cheeks and dorsum of the nose. The patient’s mother deferred chemoprevention with an oral retinoid due to the extensive side-effect profile and long-term necessity of administration.

Management also encompassed BCC surveillance every 4 months; annual digital panorex of the jaw; routine dental screening; routine developmental screening; annual follow-up with a geneticist to ensure multidisciplinary care; and annual vision, hearing, and speech-screening examinations. Strict sun-protective measures were encouraged, including wearing a hat during physical education class.

Comment

Classification and Clinical Presentation
Nevoid basal cell carcinoma syndrome is a multisystem disorder that requires close monitoring under multidisciplinary care. Evans et al⁶ defined the diagnostic criteria of NBCCS to require the presence of 2 major criteria or 1 major and 2 minor criteria. The major criteria include multiple BCCs, an odontogenic keratocyst or polyostotic bone cyst, palmar or plantar pits, ectopic calcification of the falx cerebri, and family history of NBCCS. The minor criteria are defined as congenital skeletal anomalies; macrocephaly with frontal bossing; cardiac or ovarian fibromas; medulloblastoma; lymphomesenteric cysts; and congenital malformations such as cleft lip or palate, polydactyly, or eye anomalies.⁶ The mean age of initial BCC diagnosis is 21 years, with proliferation of cancers between puberty and 35 years of age.^7,9 Our case is unique due to the patient’s young age at the time of diagnosis as well as his presentation with multiple BCCs with a darker skin type. Kimonis et al⁷ reported that approximately 20% of black patients develop their first BCC by the age of 21 years and 40% by 35 years. The presence of multiple BCCs is complicated by the limited treatment options in a pediatric patient. The patient’s inability to withstand multiple procedures contributed to our clinical decision to have multiple lesions removed under general anesthesia by a pediatric plastic surgeon.

Due to the patient’s young age of onset, we placed a great emphasis on close surveillance and management. A management protocol for pediatric patients with NBCCS was described by Bree and Shah; BCNS Colloquium Group¹⁰ (eTable). We closely followed this protocol for surveillance; however, we scheduled dermatologic examinations every 4 months due to his extensive history of BCCs.

Management
Our case presents a challenging therapeutic and management dilemma. The management of NBCCS utilizes a multitude of treatment modalities, but many of them posed cosmetic challenges in our patient such as postinflammatory hypopigmentation and the propensity for keloid formation. Although surgical excision or Mohs micrographic surgery is the standard of treatment of nodular BCCs, we were limited due to the patient’s inability to tolerate multiple surgical procedures without the use of general anesthesia.

Case reports have discussed the use of CO₂ laser resurfacing for management of multiple facial BCCs in patients with NBCCS. Doctoroff et al¹¹ treated a patient with 45 facial BCCs with full-face CO₂ laser resurfacing, and in a 10-month follow-up period the patient developed 6 new BCCs on the face. Nouri et al¹² described 3 cases of multiple BCCs on the face, trunk, and extremities treated with ultrapulse CO₂ laser with postoperative Mohs sections verifying complete histologic clearance of tumors. All 3 patients had Fitzpatrick skin type IV; their ages were 2, 16, and 35 years. Local anesthesia was used in the 2-year-old patient and intravenous sedation in the 16-year-old patient.¹² Although CO₂ laser therapy may be a practical treatment option, it posed too many cosmetic concerns in our patient.

Photodynamic therapy (PDT) is an emerging treatment option for NBCCS patients. Itkin and Gilchrest¹³ treated 2 NBCCS patients with δ-aminolevulinic acid for 1 to 5 hours prior to treatment with blue light therapy. Complete clearance was documented in 89% (8/9) of superficial BCCs and 31% (5/16) of nodular BCCs on the face, indicating that blue light treatment may reduce the cutaneous tumor burden.¹³ Oseroff et al¹⁴ reported similar success in treating 3 children with NBCCS with 20% δ-aminolevulinic acid for 24 hours under occlusion followed by red light treatment. After 1 to 3 treatments, the children had 85% to 98% total clearance, demonstrating it as a viable treatment option in young patients that yields excellent cosmetic results and is well tolerated.¹⁴ Photodynamic therapy is reported to have a low risk of carcinogenicity¹⁵; however, there has been 1 reported case of melanoma developing at the site of multiple PDT treatments.¹⁶ Thus, the risk of carcinogenicity is increasingly bothersome in NBCCS patients due to their sensitivity to exposure. The limited number of studies using topical PDT on pediatric patients, the lack of treatment protocols for pediatric patients, and the need to use general anesthesia for pediatric patients all posed limitations to the use of PDT in our case.

Imiquimod cream 5% was shown in randomized, vehicle-controlled studies to be a safe and effective treatment of superficial BCCs when used 5 days weekly for 6 weeks.¹⁷ These studies excluded patients with NBCCS; however, other studies have been completed in patients with NBCCS. Kagy and Amonette¹⁸ successfully treated 3 nonfacial BCCs in a patient with NBCCS with imiquimod cream 5% daily for 18 weeks, with complete histologic resolution of the tumors. Micali et al¹⁹ also treated 4 patients with NBCCS using imiquimod cream 5% 3 to 5 times weekly for 8 to 14 weeks. Thirteen of 17 BCCs resolved, as confirmed with histologic evaluation.¹⁹ One case report revealed a child with NBCCS who was successfully managed with topical fluorouracil and topical tretinoin for more than 10 years.²⁰ Our patient used imiquimod cream 5% 5 times weekly, which inhibited the growth of existing lesions but did not clear them entirely, as they were nodular in nature.

Chemoprevention with oral retinoids breaches a controversial treatment topic. In 1989, a case study of an NBCCS patient treated with surgical excision and oral etretinate for 12 months documented reduction of large tumors.²¹ A multicenter clinical trial reported that low-dose isotretinoin (10 mg daily) is ineffective in preventing the occurrence of new BCC formation in patients with a history of 2 or more sporadic BCCs.²² Chemoprevention with oral retinoids is well known for being effective for squamous cell carcinomas and actinic keratosis; however, the treatment is less effective for BCCs.²² Most importantly, the extensive side-effect profile and toxicity associated with long-term administration of oral retinoids prohibits many practitioners from routinely using them in pediatric NBCCS patients.

Nevoid basal cell carcinoma syndrome patients are exquisitely sensitive to ionizing radiation and the effects of UV exposure. Therefore, it is essential to emphasize the importance of sun-protective measures such as sun avoidance, broad-spectrum sunscreen use, and sun-protective clothing.

Conclusion

Nevoid basal cell carcinoma syndrome is a multisystem disorder with a notable predisposition for skin cancer. Our case demonstrates the treatment considerations in a pediatric patient with Fitzpatrick skin type V. Pediatric NBCCS patients develop BCCs at a young age and will continue to develop additional lesions throughout life; therefore, skin preservation is an important consideration when choosing the appropriate treatment regimen. Particularly in our patient, utilizing multiple strategic treatment modalities in combination with chemoprevention moving forward will be a continued management challenge. Strict adherence to a surveillance protocol is encouraged to closely monitor the systemic manifestations of the disorder.

In 1960, Gorlin and Goltz¹ first described nevoid basal cell carcinoma syndrome (NBCCS) as a distinct clinical entity with multiple basal cell carcinomas (BCCs), jaw cysts, and bifid ribs. This rare autosomal-dominant genodermatosis has a minimal prevalence of 1 case per 57,000 individuals² and no sexual predilection.³ Nevoid basal cell carcinoma syndrome is caused by a mutation in the human homolog of a Drosophila gene, patched 1 (PTCH1), which is located on chromosome 9q22.^3.4,5 The major clinical diagnostic criteria includes multiple BCCs, odontogenic keratocysts, palmar or plantar pits, ectopic calcification of the falx cerebri, and a family history of NBCCS.⁶ Basal cell carcinoma formation is affected by both skin pigmentation and sun exposure; 80% of white patients with NBCCS will develop at least 1 BCC compared to only 40% of black patients with NBCCS.⁷ Goldstein et al⁸ postulated that this disparity is associated with increased skin pigmentation providing UV radiation protection, thus decreasing the tumor burden. We report a case of an 11-year-old black boy with NBCCS to highlight the treatment considerations in pediatric cases of NBCCS.

Case Report

An 11-year-old boy with Fitzpatrick skin type V presented with a history of multiple facial lesions after undergoing excision of large keratocysts from the right maxilla, left maxilla, and right mandible. Physical examination revealed multiple light to dark brown facial papules (Figure 1), palmar and plantar pitting (Figure 2), and frontal bossing.

He was previously diagnosed with autism and his surgical history was notable only for excision of the keratocysts. The patient was not taking any medications and did not have any drug allergies. There was no maternal family history of skin cancer or related syndromes; his paternal family history was unknown. A shave biopsy was performed on a facial papule from the right nasolabial fold. Histopathologic evaluation revealed findings consistent with a pigmented nodular BCC (Figure 3). The patient was subsequently sent for magnetic resonance imaging of the brain, which demonstrated calcifications along the tentorium. Genetic consultation confirmed a heterozygous mutation of the PTCH1 gene.

Over the next 12 months, the patient had multiple biopsy-proven pigmented BCCs. Initial management of these carcinomas located on cosmetically sensitive areas, including the upper eyelid and penis, were excised by a pediatric plastic surgeon. A truncal carcinoma was treated with electrodesiccation and curettage, which resulted in keloid formation. Early suspicious lesions were treated with imiquimod cream 5% 5 times weekly in combination with the prophylactic use of tretinoin cream 0.1%. Despite this treatment regimen, the patient continued to demonstrate multiple small clinical pigmented BCCs along the malar surfaces of the cheeks and dorsum of the nose. The patient’s mother deferred chemoprevention with an oral retinoid due to the extensive side-effect profile and long-term necessity of administration.

Management also encompassed BCC surveillance every 4 months; annual digital panorex of the jaw; routine dental screening; routine developmental screening; annual follow-up with a geneticist to ensure multidisciplinary care; and annual vision, hearing, and speech-screening examinations. Strict sun-protective measures were encouraged, including wearing a hat during physical education class.

Comment

Classification and Clinical Presentation
Nevoid basal cell carcinoma syndrome is a multisystem disorder that requires close monitoring under multidisciplinary care. Evans et al⁶ defined the diagnostic criteria of NBCCS to require the presence of 2 major criteria or 1 major and 2 minor criteria. The major criteria include multiple BCCs, an odontogenic keratocyst or polyostotic bone cyst, palmar or plantar pits, ectopic calcification of the falx cerebri, and family history of NBCCS. The minor criteria are defined as congenital skeletal anomalies; macrocephaly with frontal bossing; cardiac or ovarian fibromas; medulloblastoma; lymphomesenteric cysts; and congenital malformations such as cleft lip or palate, polydactyly, or eye anomalies.⁶ The mean age of initial BCC diagnosis is 21 years, with proliferation of cancers between puberty and 35 years of age.^7,9 Our case is unique due to the patient’s young age at the time of diagnosis as well as his presentation with multiple BCCs with a darker skin type. Kimonis et al⁷ reported that approximately 20% of black patients develop their first BCC by the age of 21 years and 40% by 35 years. The presence of multiple BCCs is complicated by the limited treatment options in a pediatric patient. The patient’s inability to withstand multiple procedures contributed to our clinical decision to have multiple lesions removed under general anesthesia by a pediatric plastic surgeon.

Due to the patient’s young age of onset, we placed a great emphasis on close surveillance and management. A management protocol for pediatric patients with NBCCS was described by Bree and Shah; BCNS Colloquium Group¹⁰ (eTable). We closely followed this protocol for surveillance; however, we scheduled dermatologic examinations every 4 months due to his extensive history of BCCs.

Management
Our case presents a challenging therapeutic and management dilemma. The management of NBCCS utilizes a multitude of treatment modalities, but many of them posed cosmetic challenges in our patient such as postinflammatory hypopigmentation and the propensity for keloid formation. Although surgical excision or Mohs micrographic surgery is the standard of treatment of nodular BCCs, we were limited due to the patient’s inability to tolerate multiple surgical procedures without the use of general anesthesia.

Case reports have discussed the use of CO₂ laser resurfacing for management of multiple facial BCCs in patients with NBCCS. Doctoroff et al¹¹ treated a patient with 45 facial BCCs with full-face CO₂ laser resurfacing, and in a 10-month follow-up period the patient developed 6 new BCCs on the face. Nouri et al¹² described 3 cases of multiple BCCs on the face, trunk, and extremities treated with ultrapulse CO₂ laser with postoperative Mohs sections verifying complete histologic clearance of tumors. All 3 patients had Fitzpatrick skin type IV; their ages were 2, 16, and 35 years. Local anesthesia was used in the 2-year-old patient and intravenous sedation in the 16-year-old patient.¹² Although CO₂ laser therapy may be a practical treatment option, it posed too many cosmetic concerns in our patient.

Photodynamic therapy (PDT) is an emerging treatment option for NBCCS patients. Itkin and Gilchrest¹³ treated 2 NBCCS patients with δ-aminolevulinic acid for 1 to 5 hours prior to treatment with blue light therapy. Complete clearance was documented in 89% (8/9) of superficial BCCs and 31% (5/16) of nodular BCCs on the face, indicating that blue light treatment may reduce the cutaneous tumor burden.¹³ Oseroff et al¹⁴ reported similar success in treating 3 children with NBCCS with 20% δ-aminolevulinic acid for 24 hours under occlusion followed by red light treatment. After 1 to 3 treatments, the children had 85% to 98% total clearance, demonstrating it as a viable treatment option in young patients that yields excellent cosmetic results and is well tolerated.¹⁴ Photodynamic therapy is reported to have a low risk of carcinogenicity¹⁵; however, there has been 1 reported case of melanoma developing at the site of multiple PDT treatments.¹⁶ Thus, the risk of carcinogenicity is increasingly bothersome in NBCCS patients due to their sensitivity to exposure. The limited number of studies using topical PDT on pediatric patients, the lack of treatment protocols for pediatric patients, and the need to use general anesthesia for pediatric patients all posed limitations to the use of PDT in our case.

Imiquimod cream 5% was shown in randomized, vehicle-controlled studies to be a safe and effective treatment of superficial BCCs when used 5 days weekly for 6 weeks.¹⁷ These studies excluded patients with NBCCS; however, other studies have been completed in patients with NBCCS. Kagy and Amonette¹⁸ successfully treated 3 nonfacial BCCs in a patient with NBCCS with imiquimod cream 5% daily for 18 weeks, with complete histologic resolution of the tumors. Micali et al¹⁹ also treated 4 patients with NBCCS using imiquimod cream 5% 3 to 5 times weekly for 8 to 14 weeks. Thirteen of 17 BCCs resolved, as confirmed with histologic evaluation.¹⁹ One case report revealed a child with NBCCS who was successfully managed with topical fluorouracil and topical tretinoin for more than 10 years.²⁰ Our patient used imiquimod cream 5% 5 times weekly, which inhibited the growth of existing lesions but did not clear them entirely, as they were nodular in nature.

Chemoprevention with oral retinoids breaches a controversial treatment topic. In 1989, a case study of an NBCCS patient treated with surgical excision and oral etretinate for 12 months documented reduction of large tumors.²¹ A multicenter clinical trial reported that low-dose isotretinoin (10 mg daily) is ineffective in preventing the occurrence of new BCC formation in patients with a history of 2 or more sporadic BCCs.²² Chemoprevention with oral retinoids is well known for being effective for squamous cell carcinomas and actinic keratosis; however, the treatment is less effective for BCCs.²² Most importantly, the extensive side-effect profile and toxicity associated with long-term administration of oral retinoids prohibits many practitioners from routinely using them in pediatric NBCCS patients.

Nevoid basal cell carcinoma syndrome patients are exquisitely sensitive to ionizing radiation and the effects of UV exposure. Therefore, it is essential to emphasize the importance of sun-protective measures such as sun avoidance, broad-spectrum sunscreen use, and sun-protective clothing.

Conclusion

Nevoid basal cell carcinoma syndrome is a multisystem disorder with a notable predisposition for skin cancer. Our case demonstrates the treatment considerations in a pediatric patient with Fitzpatrick skin type V. Pediatric NBCCS patients develop BCCs at a young age and will continue to develop additional lesions throughout life; therefore, skin preservation is an important consideration when choosing the appropriate treatment regimen. Particularly in our patient, utilizing multiple strategic treatment modalities in combination with chemoprevention moving forward will be a continued management challenge. Strict adherence to a surveillance protocol is encouraged to closely monitor the systemic manifestations of the disorder.

MONTREAL – African American breast cancer survivors who participated in fitness tracking and an online support program saw small but significant reductions in weight and improvement in quality of life, according to a new study.

Further, patients who reported a low baseline quality of life (QOL) achieved as much or more weight loss as did those whose QOL was initially high, said Jeanne Ferrante, MD, MPH, professor of family medicine and community health at Robert Wood Johnson Medical School, New Brunswick, N.J.

shironosov/Thinkstock

Dr. Ferrante reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MONTREAL – African American breast cancer survivors who participated in fitness tracking and an online support program saw small but significant reductions in weight and improvement in quality of life, according to a new study.

Further, patients who reported a low baseline quality of life (QOL) achieved as much or more weight loss as did those whose QOL was initially high, said Jeanne Ferrante, MD, MPH, professor of family medicine and community health at Robert Wood Johnson Medical School, New Brunswick, N.J.

shironosov/Thinkstock

Dr. Ferrante reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MONTREAL – African American breast cancer survivors who participated in fitness tracking and an online support program saw small but significant reductions in weight and improvement in quality of life, according to a new study.

Further, patients who reported a low baseline quality of life (QOL) achieved as much or more weight loss as did those whose QOL was initially high, said Jeanne Ferrante, MD, MPH, professor of family medicine and community health at Robert Wood Johnson Medical School, New Brunswick, N.J.

shironosov/Thinkstock

Dr. Ferrante reported no conflicts of interest.

[email protected]

On Twitter @karioakes

Case Report

A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules consistent with lichen planus (LP) on the volar wrists, extensor elbows, and bilateral lower legs of 3 years’ duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months’ duration (Figure 1). She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. A complete physical examination was performed. Age-appropriate screening for malignancy was negative. Hepatitis B and C antibody serologies were negative. Her medications at the time included risedronate and atenolol, which she had been taking for several years.

Punch biopsies from perilesional skin were submitted for hematoxylin and eosin staining and direct immunofluorescence (DIF). Histopathology showed a subepidermal blistering disease with tissue eosinophilia consistent with lichen planus pemphigoides (LPP)(Figure 2); direct immunofluorescence was positive for IgG, C3, and type IV collagen at the dermoepidermal junction. Serum BP180 was positive at 51 U/mL (reference range, <14 U/mL) and BP230 was negative. She was then started on tetracycline (500 mg twice daily), nicotinamide (500 mg twice daily), prednisone (5 mg daily), and dapsone (100 mg daily).

After 3 months without improvement, tetracycline and nicotinamide were discontinued, prednisone was increased to 10 mg daily, and dapsone was continued. A repeat biopsy was taken from a new area of involvement on the left lower leg, which revealed a psoriasiform dermatitis with interface changes. The DIF was positive for IgG and C3 along the basement membrane. A serum indirect immunofluorescence for BP180 also was positive.

The patient developed mild hemolytic anemia on dapsone; the medication was eventually discontinued. Subsequent treatments included adequate trials of azathioprine, mycophenolate mofetil, and hydroxychloroquine. Azathioprine (150 mg daily) and hydroxychloroquine (400 mg daily) treatment failed. She initially improved on mycophenolate mofetil (500 mg in the morning and 1000 mg in the evening) with flattening of the papules on the arms and legs and decreased erythema. However, mycophenolate mofetil eventually lost its efficacy and was discontinued.

Because several medications failed (ie, tetracycline, nicotinamide, prednisone, dapsone, azathioprine, mycophenolate mofetil, hydroxychloroquine), she was started on ustekinumab (45 mg) initial loading dose by subcutaneous injection (patient’s weight, 63 kg). At 4 weeks, the patient was given the second subcutaneous injection of ustekinumab (45 mg). She experienced marked improvement with no new lesions. The prior lesions also had decreased in size and were only slightly pink. The prednisone dose was tapered to 5 mg daily.

She had near-complete resolution of the skin lesions 12 weeks after the second dose of ustekinumab. Since then, she has had some recrudescence of the papulosquamous lesions but no vesicles or bullae. With the exception of occasional scattered pink papules on the forearms, her condition greatly improved on ustekinumab. She is no longer taking any of the other medications with the exception of prednisone (down to 1 mg daily) with a plan to gradually taper completely off of it.

Comment

Clinical Presentation
Lichen planus pemphigoides is a rare autoimmune subepidermal blistering disease with few cases reported in the literature. It is considered a clinical variation of bullous pemphigoid (BP) or a coexistence of LP and BP.^1,2 It is characterized by bullous lesions developing on LP papules as well as on clinically uninvolved areas of the skin. It has been reported that LPP is provoked by several medications including cinnarizine, captopril, ramipril, simvastatin, psoralen plus UVA, and antituberculous medications (eg, isoniazid, rifampin, ethambutol, pyrazinamide).¹ Risedronate or atenolol have not been reported to cause LPP, LP, or BP; however, according to Litt,³ a lichenoid drug eruption has been associated with atenolol. Furthermore, some cases of LPP demonstrate overlapping characteristics with paraneoplastic pemphigus and have been associated with internal malignancy. Hamada et al⁴ described a case of LPP coupled with colon adenocarcinoma and numerous keratoacanthomas. The earliest depiction of the coexistence of a case of mainstream LP complicated by an extensive bullous eruption was by Kaposi⁵ in 1892. He coined the term lichen ruber pemphigoides.⁵

Compared to BP, LPP is believed to affect a younger age group and have a less serious clinical course. The mean age of onset of LPP is in the third to fourth decades of life, while BP typically presents in the sixth decade. When comparing the location of bullae in LPP versus BP, the lesions of LPP tend to occur on the limbs, while BP tends to occur on the trunk.⁶

Clinically, LPP is distinguished by the existence of bullous lesions developing atop of the lesions of LP as well as on normal skin, with the latter being more commonplace. A classic example of LPP is characterized by an initial episode of traditional LP lesions often having severe pruritus, with or without patches of erythema, with the sudden eruption of tense bullae. These bullae commonly appear on the extremities and can appear over the normal skin, erythematous patches, or preexisting papules.⁷ In the atypical clinical presentations of this dubious skin condition, the bullae may only be seen on the lesions of LP.⁸ There also could be a lichenoid erythrodermic manifestation of a bullous eruption.⁹

Oral lesions of LPP have been described but had not been studied immunopathologically until Allen et al¹⁰ portrayed a 59-year-old man with cutaneous and oral lesions of LPP. They performed biopsies on the oral lesions and examined them by routine light microscopy and immunofluorescent techniques. The fine keratotic striae on the anterior buccal mucosal lesions were clinically consistent with oral LP. Perilesional tissue in conjunction with ulceration of the posterior buccal mucosa demonstrated histologic and immunopathologic alterations consistent with BP.¹⁰

Histopathology
Histopathologically, the lesions of LP show a bandlike lymphohistiocytic infiltrate, colloid bodies in the dermis, irregular acanthosis with saw-toothed rete ridges, orthokeratosis, wedge-shaped hypergranulosis, and liquefaction degeneration of the basal layer. Direct immunofluorescence shows mainly IgM and C3 deposited on colloid bodies, fibrin, and fibrinogen.¹¹ The histopathology of the bullous lesion of LPP depicts a subepidermal bulla with variable diffuse or sparse lymphohistiocytic infiltrate and frequent eosinophils with or without neutrophils in the upper dermis. The existence of C3 alone or with IgG along the dermoepidermal junction gives confirmation on DIF.⁷

Autoantibodies
The expression of IgG autoantibodies directed against the basement membrane zone distinguishes LPP from bullous LP.² IgG autoantibodies to either one or both the 230-kDa and 180-kDa BP (type XVII collagen) antigens has been demonstrated with LPP.^4,12-14 Hamada et al⁴ described a histologic pattern more consistent with paraneoplastic pemphigus. It has been suggested that injury to the basal cells in LP or damage due to other courses of therapy such as psoralen plus UVA unveil suppressed antigenic determinants or produce new antigens, leading to antibody development and production of BP.^12,15

Zillikens et al² performed a study to identify the target antigen of LPP autoantibodies. They used sera from patients with LPP (n=4) and stained the epidermal side of salt-split human skin in a configuration identical to BP sera. In BP, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. They demonstrated that sera from BP patients largely reacted with a set of 4 epitopes (MCW-0 through MCW-3) grouped within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, LPP sera also were compellingly reactive with recombinant BP180 NC16A. Lichen planus pemphigoides epitopes were additionally mapped using a series of overlapping recombinant segments of the NC16A domain. The authors demonstrated that all LPP sera reacted with amino acids 46 through 59 of domain NC16A, a protein portion that was previously shown to be unreactive with BP sera. In addition, they showed that 2 LPP sera reacted with the immunodominant antigenic region related to BP. Furthermore, they identified a unique epitope within the BP180 NC16A domain—MCW-4—which was distinctively recognized by sera from patients with LPP.²

Pathogenesis
The pathogenesis of both LP and BP has been linked to multiple cytokines that induce apoptosis in basal keratinocytes. Implicated cytokines include IFN-γ, tumor necrosis factor α (TNF-α), IL-1, IL-6, and IL-8, as well as other apoptosis-related molecules, such as Fas/Apo-1 and Bcl-2 in LP.^16-18 Soluble E-selectin, vascular endothelial growth factor, IL-1β, IL-8, IL-5, transforming growth factor β1, and TNF-α were found to be elevated in either blister fluid or sera of BP patients.^15-17

Management
Lichen planus pemphigoides usually responds well to traditional therapies, with systemic steroids being the most efficacious treatment of extensive disease.^12,13 Other options include tetracycline and nicotinamide, isotretinoin, dapsone, and immunosuppressive drugs such as systemic cortico-steroids.¹² Demirçay et al¹² described a patient with skin lesions that rapidly cleared after the administration of oral methylprednisolone (48 mg/d) and oral dapsone (100 mg/d). The methylprednisolone and dapsone were withdrawn after 12 and 16 weeks, respectively. There was no recurrence during the 1-year follow-up period.¹²Kolb-Mäurer et al¹⁹ described a patient who was treated with pulsed intravenous corticosteroids and continued to develop new papular and vesicular skin lesions. However, when oral acitretin was added to the patient’s regimen, the skin lesions cleared.¹⁹ There are several case reports of the successful use of hydroxychloroquine in LP.^20,21

Cutaneous, nail, and oral LP also can be treated with TNF-α inhibitors (eg, adalimumab, etanercept) with resolution of lesions.^22-25 However, we have not been able to find any reports of treating LPP with biologic medications in a search of PubMed articles indexed for MEDLINE using the terms lichen planus pemphigoides and biologic treatments/therapies. Given the fact that TNF-α and other inflammatory cytokines are involved in the pathogenesis of BP and LP, it is feasible that they also may be involved in the pathogenesis of LPP.

In our patient with cutaneous LPP, we chose to use ustekinumab instead of a primary TNF-α inhibitor because ustekinumab indirectly blocks TNF-α, as well as other proinflammatory cytokines such as IFN-γ, IL-17, and IL-22, which also could have played a role in the patient’s disease. Our goal was to use ustekinumab as a potential corticosteroid-sparing agent. Ustekinumab greatly improved her skin condition and allowed us to discontinue other medications.

Case Report

A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules consistent with lichen planus (LP) on the volar wrists, extensor elbows, and bilateral lower legs of 3 years’ duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months’ duration (Figure 1). She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. A complete physical examination was performed. Age-appropriate screening for malignancy was negative. Hepatitis B and C antibody serologies were negative. Her medications at the time included risedronate and atenolol, which she had been taking for several years.

Punch biopsies from perilesional skin were submitted for hematoxylin and eosin staining and direct immunofluorescence (DIF). Histopathology showed a subepidermal blistering disease with tissue eosinophilia consistent with lichen planus pemphigoides (LPP)(Figure 2); direct immunofluorescence was positive for IgG, C3, and type IV collagen at the dermoepidermal junction. Serum BP180 was positive at 51 U/mL (reference range, <14 U/mL) and BP230 was negative. She was then started on tetracycline (500 mg twice daily), nicotinamide (500 mg twice daily), prednisone (5 mg daily), and dapsone (100 mg daily).

After 3 months without improvement, tetracycline and nicotinamide were discontinued, prednisone was increased to 10 mg daily, and dapsone was continued. A repeat biopsy was taken from a new area of involvement on the left lower leg, which revealed a psoriasiform dermatitis with interface changes. The DIF was positive for IgG and C3 along the basement membrane. A serum indirect immunofluorescence for BP180 also was positive.

The patient developed mild hemolytic anemia on dapsone; the medication was eventually discontinued. Subsequent treatments included adequate trials of azathioprine, mycophenolate mofetil, and hydroxychloroquine. Azathioprine (150 mg daily) and hydroxychloroquine (400 mg daily) treatment failed. She initially improved on mycophenolate mofetil (500 mg in the morning and 1000 mg in the evening) with flattening of the papules on the arms and legs and decreased erythema. However, mycophenolate mofetil eventually lost its efficacy and was discontinued.

Because several medications failed (ie, tetracycline, nicotinamide, prednisone, dapsone, azathioprine, mycophenolate mofetil, hydroxychloroquine), she was started on ustekinumab (45 mg) initial loading dose by subcutaneous injection (patient’s weight, 63 kg). At 4 weeks, the patient was given the second subcutaneous injection of ustekinumab (45 mg). She experienced marked improvement with no new lesions. The prior lesions also had decreased in size and were only slightly pink. The prednisone dose was tapered to 5 mg daily.

She had near-complete resolution of the skin lesions 12 weeks after the second dose of ustekinumab. Since then, she has had some recrudescence of the papulosquamous lesions but no vesicles or bullae. With the exception of occasional scattered pink papules on the forearms, her condition greatly improved on ustekinumab. She is no longer taking any of the other medications with the exception of prednisone (down to 1 mg daily) with a plan to gradually taper completely off of it.

Comment

Clinical Presentation
Lichen planus pemphigoides is a rare autoimmune subepidermal blistering disease with few cases reported in the literature. It is considered a clinical variation of bullous pemphigoid (BP) or a coexistence of LP and BP.^1,2 It is characterized by bullous lesions developing on LP papules as well as on clinically uninvolved areas of the skin. It has been reported that LPP is provoked by several medications including cinnarizine, captopril, ramipril, simvastatin, psoralen plus UVA, and antituberculous medications (eg, isoniazid, rifampin, ethambutol, pyrazinamide).¹ Risedronate or atenolol have not been reported to cause LPP, LP, or BP; however, according to Litt,³ a lichenoid drug eruption has been associated with atenolol. Furthermore, some cases of LPP demonstrate overlapping characteristics with paraneoplastic pemphigus and have been associated with internal malignancy. Hamada et al⁴ described a case of LPP coupled with colon adenocarcinoma and numerous keratoacanthomas. The earliest depiction of the coexistence of a case of mainstream LP complicated by an extensive bullous eruption was by Kaposi⁵ in 1892. He coined the term lichen ruber pemphigoides.⁵

Compared to BP, LPP is believed to affect a younger age group and have a less serious clinical course. The mean age of onset of LPP is in the third to fourth decades of life, while BP typically presents in the sixth decade. When comparing the location of bullae in LPP versus BP, the lesions of LPP tend to occur on the limbs, while BP tends to occur on the trunk.⁶

Clinically, LPP is distinguished by the existence of bullous lesions developing atop of the lesions of LP as well as on normal skin, with the latter being more commonplace. A classic example of LPP is characterized by an initial episode of traditional LP lesions often having severe pruritus, with or without patches of erythema, with the sudden eruption of tense bullae. These bullae commonly appear on the extremities and can appear over the normal skin, erythematous patches, or preexisting papules.⁷ In the atypical clinical presentations of this dubious skin condition, the bullae may only be seen on the lesions of LP.⁸ There also could be a lichenoid erythrodermic manifestation of a bullous eruption.⁹

Oral lesions of LPP have been described but had not been studied immunopathologically until Allen et al¹⁰ portrayed a 59-year-old man with cutaneous and oral lesions of LPP. They performed biopsies on the oral lesions and examined them by routine light microscopy and immunofluorescent techniques. The fine keratotic striae on the anterior buccal mucosal lesions were clinically consistent with oral LP. Perilesional tissue in conjunction with ulceration of the posterior buccal mucosa demonstrated histologic and immunopathologic alterations consistent with BP.¹⁰

Histopathology
Histopathologically, the lesions of LP show a bandlike lymphohistiocytic infiltrate, colloid bodies in the dermis, irregular acanthosis with saw-toothed rete ridges, orthokeratosis, wedge-shaped hypergranulosis, and liquefaction degeneration of the basal layer. Direct immunofluorescence shows mainly IgM and C3 deposited on colloid bodies, fibrin, and fibrinogen.¹¹ The histopathology of the bullous lesion of LPP depicts a subepidermal bulla with variable diffuse or sparse lymphohistiocytic infiltrate and frequent eosinophils with or without neutrophils in the upper dermis. The existence of C3 alone or with IgG along the dermoepidermal junction gives confirmation on DIF.⁷

Autoantibodies
The expression of IgG autoantibodies directed against the basement membrane zone distinguishes LPP from bullous LP.² IgG autoantibodies to either one or both the 230-kDa and 180-kDa BP (type XVII collagen) antigens has been demonstrated with LPP.^4,12-14 Hamada et al⁴ described a histologic pattern more consistent with paraneoplastic pemphigus. It has been suggested that injury to the basal cells in LP or damage due to other courses of therapy such as psoralen plus UVA unveil suppressed antigenic determinants or produce new antigens, leading to antibody development and production of BP.^12,15

Zillikens et al² performed a study to identify the target antigen of LPP autoantibodies. They used sera from patients with LPP (n=4) and stained the epidermal side of salt-split human skin in a configuration identical to BP sera. In BP, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. They demonstrated that sera from BP patients largely reacted with a set of 4 epitopes (MCW-0 through MCW-3) grouped within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, LPP sera also were compellingly reactive with recombinant BP180 NC16A. Lichen planus pemphigoides epitopes were additionally mapped using a series of overlapping recombinant segments of the NC16A domain. The authors demonstrated that all LPP sera reacted with amino acids 46 through 59 of domain NC16A, a protein portion that was previously shown to be unreactive with BP sera. In addition, they showed that 2 LPP sera reacted with the immunodominant antigenic region related to BP. Furthermore, they identified a unique epitope within the BP180 NC16A domain—MCW-4—which was distinctively recognized by sera from patients with LPP.²

Pathogenesis
The pathogenesis of both LP and BP has been linked to multiple cytokines that induce apoptosis in basal keratinocytes. Implicated cytokines include IFN-γ, tumor necrosis factor α (TNF-α), IL-1, IL-6, and IL-8, as well as other apoptosis-related molecules, such as Fas/Apo-1 and Bcl-2 in LP.^16-18 Soluble E-selectin, vascular endothelial growth factor, IL-1β, IL-8, IL-5, transforming growth factor β1, and TNF-α were found to be elevated in either blister fluid or sera of BP patients.^15-17

Management
Lichen planus pemphigoides usually responds well to traditional therapies, with systemic steroids being the most efficacious treatment of extensive disease.^12,13 Other options include tetracycline and nicotinamide, isotretinoin, dapsone, and immunosuppressive drugs such as systemic cortico-steroids.¹² Demirçay et al¹² described a patient with skin lesions that rapidly cleared after the administration of oral methylprednisolone (48 mg/d) and oral dapsone (100 mg/d). The methylprednisolone and dapsone were withdrawn after 12 and 16 weeks, respectively. There was no recurrence during the 1-year follow-up period.¹²Kolb-Mäurer et al¹⁹ described a patient who was treated with pulsed intravenous corticosteroids and continued to develop new papular and vesicular skin lesions. However, when oral acitretin was added to the patient’s regimen, the skin lesions cleared.¹⁹ There are several case reports of the successful use of hydroxychloroquine in LP.^20,21

Cutaneous, nail, and oral LP also can be treated with TNF-α inhibitors (eg, adalimumab, etanercept) with resolution of lesions.^22-25 However, we have not been able to find any reports of treating LPP with biologic medications in a search of PubMed articles indexed for MEDLINE using the terms lichen planus pemphigoides and biologic treatments/therapies. Given the fact that TNF-α and other inflammatory cytokines are involved in the pathogenesis of BP and LP, it is feasible that they also may be involved in the pathogenesis of LPP.

In our patient with cutaneous LPP, we chose to use ustekinumab instead of a primary TNF-α inhibitor because ustekinumab indirectly blocks TNF-α, as well as other proinflammatory cytokines such as IFN-γ, IL-17, and IL-22, which also could have played a role in the patient’s disease. Our goal was to use ustekinumab as a potential corticosteroid-sparing agent. Ustekinumab greatly improved her skin condition and allowed us to discontinue other medications.

Case Report

A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules consistent with lichen planus (LP) on the volar wrists, extensor elbows, and bilateral lower legs of 3 years’ duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months’ duration (Figure 1). She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. A complete physical examination was performed. Age-appropriate screening for malignancy was negative. Hepatitis B and C antibody serologies were negative. Her medications at the time included risedronate and atenolol, which she had been taking for several years.

Punch biopsies from perilesional skin were submitted for hematoxylin and eosin staining and direct immunofluorescence (DIF). Histopathology showed a subepidermal blistering disease with tissue eosinophilia consistent with lichen planus pemphigoides (LPP)(Figure 2); direct immunofluorescence was positive for IgG, C3, and type IV collagen at the dermoepidermal junction. Serum BP180 was positive at 51 U/mL (reference range, <14 U/mL) and BP230 was negative. She was then started on tetracycline (500 mg twice daily), nicotinamide (500 mg twice daily), prednisone (5 mg daily), and dapsone (100 mg daily).

After 3 months without improvement, tetracycline and nicotinamide were discontinued, prednisone was increased to 10 mg daily, and dapsone was continued. A repeat biopsy was taken from a new area of involvement on the left lower leg, which revealed a psoriasiform dermatitis with interface changes. The DIF was positive for IgG and C3 along the basement membrane. A serum indirect immunofluorescence for BP180 also was positive.

The patient developed mild hemolytic anemia on dapsone; the medication was eventually discontinued. Subsequent treatments included adequate trials of azathioprine, mycophenolate mofetil, and hydroxychloroquine. Azathioprine (150 mg daily) and hydroxychloroquine (400 mg daily) treatment failed. She initially improved on mycophenolate mofetil (500 mg in the morning and 1000 mg in the evening) with flattening of the papules on the arms and legs and decreased erythema. However, mycophenolate mofetil eventually lost its efficacy and was discontinued.

Because several medications failed (ie, tetracycline, nicotinamide, prednisone, dapsone, azathioprine, mycophenolate mofetil, hydroxychloroquine), she was started on ustekinumab (45 mg) initial loading dose by subcutaneous injection (patient’s weight, 63 kg). At 4 weeks, the patient was given the second subcutaneous injection of ustekinumab (45 mg). She experienced marked improvement with no new lesions. The prior lesions also had decreased in size and were only slightly pink. The prednisone dose was tapered to 5 mg daily.

She had near-complete resolution of the skin lesions 12 weeks after the second dose of ustekinumab. Since then, she has had some recrudescence of the papulosquamous lesions but no vesicles or bullae. With the exception of occasional scattered pink papules on the forearms, her condition greatly improved on ustekinumab. She is no longer taking any of the other medications with the exception of prednisone (down to 1 mg daily) with a plan to gradually taper completely off of it.

Comment

Clinical Presentation
Lichen planus pemphigoides is a rare autoimmune subepidermal blistering disease with few cases reported in the literature. It is considered a clinical variation of bullous pemphigoid (BP) or a coexistence of LP and BP.^1,2 It is characterized by bullous lesions developing on LP papules as well as on clinically uninvolved areas of the skin. It has been reported that LPP is provoked by several medications including cinnarizine, captopril, ramipril, simvastatin, psoralen plus UVA, and antituberculous medications (eg, isoniazid, rifampin, ethambutol, pyrazinamide).¹ Risedronate or atenolol have not been reported to cause LPP, LP, or BP; however, according to Litt,³ a lichenoid drug eruption has been associated with atenolol. Furthermore, some cases of LPP demonstrate overlapping characteristics with paraneoplastic pemphigus and have been associated with internal malignancy. Hamada et al⁴ described a case of LPP coupled with colon adenocarcinoma and numerous keratoacanthomas. The earliest depiction of the coexistence of a case of mainstream LP complicated by an extensive bullous eruption was by Kaposi⁵ in 1892. He coined the term lichen ruber pemphigoides.⁵

Compared to BP, LPP is believed to affect a younger age group and have a less serious clinical course. The mean age of onset of LPP is in the third to fourth decades of life, while BP typically presents in the sixth decade. When comparing the location of bullae in LPP versus BP, the lesions of LPP tend to occur on the limbs, while BP tends to occur on the trunk.⁶

Clinically, LPP is distinguished by the existence of bullous lesions developing atop of the lesions of LP as well as on normal skin, with the latter being more commonplace. A classic example of LPP is characterized by an initial episode of traditional LP lesions often having severe pruritus, with or without patches of erythema, with the sudden eruption of tense bullae. These bullae commonly appear on the extremities and can appear over the normal skin, erythematous patches, or preexisting papules.⁷ In the atypical clinical presentations of this dubious skin condition, the bullae may only be seen on the lesions of LP.⁸ There also could be a lichenoid erythrodermic manifestation of a bullous eruption.⁹

Oral lesions of LPP have been described but had not been studied immunopathologically until Allen et al¹⁰ portrayed a 59-year-old man with cutaneous and oral lesions of LPP. They performed biopsies on the oral lesions and examined them by routine light microscopy and immunofluorescent techniques. The fine keratotic striae on the anterior buccal mucosal lesions were clinically consistent with oral LP. Perilesional tissue in conjunction with ulceration of the posterior buccal mucosa demonstrated histologic and immunopathologic alterations consistent with BP.¹⁰

Histopathology
Histopathologically, the lesions of LP show a bandlike lymphohistiocytic infiltrate, colloid bodies in the dermis, irregular acanthosis with saw-toothed rete ridges, orthokeratosis, wedge-shaped hypergranulosis, and liquefaction degeneration of the basal layer. Direct immunofluorescence shows mainly IgM and C3 deposited on colloid bodies, fibrin, and fibrinogen.¹¹ The histopathology of the bullous lesion of LPP depicts a subepidermal bulla with variable diffuse or sparse lymphohistiocytic infiltrate and frequent eosinophils with or without neutrophils in the upper dermis. The existence of C3 alone or with IgG along the dermoepidermal junction gives confirmation on DIF.⁷

Autoantibodies
The expression of IgG autoantibodies directed against the basement membrane zone distinguishes LPP from bullous LP.² IgG autoantibodies to either one or both the 230-kDa and 180-kDa BP (type XVII collagen) antigens has been demonstrated with LPP.^4,12-14 Hamada et al⁴ described a histologic pattern more consistent with paraneoplastic pemphigus. It has been suggested that injury to the basal cells in LP or damage due to other courses of therapy such as psoralen plus UVA unveil suppressed antigenic determinants or produce new antigens, leading to antibody development and production of BP.^12,15

Zillikens et al² performed a study to identify the target antigen of LPP autoantibodies. They used sera from patients with LPP (n=4) and stained the epidermal side of salt-split human skin in a configuration identical to BP sera. In BP, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. They demonstrated that sera from BP patients largely reacted with a set of 4 epitopes (MCW-0 through MCW-3) grouped within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, LPP sera also were compellingly reactive with recombinant BP180 NC16A. Lichen planus pemphigoides epitopes were additionally mapped using a series of overlapping recombinant segments of the NC16A domain. The authors demonstrated that all LPP sera reacted with amino acids 46 through 59 of domain NC16A, a protein portion that was previously shown to be unreactive with BP sera. In addition, they showed that 2 LPP sera reacted with the immunodominant antigenic region related to BP. Furthermore, they identified a unique epitope within the BP180 NC16A domain—MCW-4—which was distinctively recognized by sera from patients with LPP.²

Pathogenesis
The pathogenesis of both LP and BP has been linked to multiple cytokines that induce apoptosis in basal keratinocytes. Implicated cytokines include IFN-γ, tumor necrosis factor α (TNF-α), IL-1, IL-6, and IL-8, as well as other apoptosis-related molecules, such as Fas/Apo-1 and Bcl-2 in LP.^16-18 Soluble E-selectin, vascular endothelial growth factor, IL-1β, IL-8, IL-5, transforming growth factor β1, and TNF-α were found to be elevated in either blister fluid or sera of BP patients.^15-17

Management
Lichen planus pemphigoides usually responds well to traditional therapies, with systemic steroids being the most efficacious treatment of extensive disease.^12,13 Other options include tetracycline and nicotinamide, isotretinoin, dapsone, and immunosuppressive drugs such as systemic cortico-steroids.¹² Demirçay et al¹² described a patient with skin lesions that rapidly cleared after the administration of oral methylprednisolone (48 mg/d) and oral dapsone (100 mg/d). The methylprednisolone and dapsone were withdrawn after 12 and 16 weeks, respectively. There was no recurrence during the 1-year follow-up period.¹²Kolb-Mäurer et al¹⁹ described a patient who was treated with pulsed intravenous corticosteroids and continued to develop new papular and vesicular skin lesions. However, when oral acitretin was added to the patient’s regimen, the skin lesions cleared.¹⁹ There are several case reports of the successful use of hydroxychloroquine in LP.^20,21

Cutaneous, nail, and oral LP also can be treated with TNF-α inhibitors (eg, adalimumab, etanercept) with resolution of lesions.^22-25 However, we have not been able to find any reports of treating LPP with biologic medications in a search of PubMed articles indexed for MEDLINE using the terms lichen planus pemphigoides and biologic treatments/therapies. Given the fact that TNF-α and other inflammatory cytokines are involved in the pathogenesis of BP and LP, it is feasible that they also may be involved in the pathogenesis of LPP.

In our patient with cutaneous LPP, we chose to use ustekinumab instead of a primary TNF-α inhibitor because ustekinumab indirectly blocks TNF-α, as well as other proinflammatory cytokines such as IFN-γ, IL-17, and IL-22, which also could have played a role in the patient’s disease. Our goal was to use ustekinumab as a potential corticosteroid-sparing agent. Ustekinumab greatly improved her skin condition and allowed us to discontinue other medications.

TORONTO – The implanted phrenic-nerve stimulation device that received Food and Drug Administration marketing approval in October 2017 for treating central sleep apnea has now shown safety and efficacy out to 18 months of continuous use in 102 patients.

After 18 months of treatment with the Remede System, patients’ outcomes remained stable and patients continued to see the improvements they had experienced after 6 and 12 months of treatment. These improvements included significant average reductions from baseline in apnea-hypopnea index and central apnea index and significant increases in oxygenation and sleep quality, Andrew C. Kao, MD, said at the CHEST annual meeting.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

TORONTO – The implanted phrenic-nerve stimulation device that received Food and Drug Administration marketing approval in October 2017 for treating central sleep apnea has now shown safety and efficacy out to 18 months of continuous use in 102 patients.

After 18 months of treatment with the Remede System, patients’ outcomes remained stable and patients continued to see the improvements they had experienced after 6 and 12 months of treatment. These improvements included significant average reductions from baseline in apnea-hypopnea index and central apnea index and significant increases in oxygenation and sleep quality, Andrew C. Kao, MD, said at the CHEST annual meeting.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

TORONTO – The implanted phrenic-nerve stimulation device that received Food and Drug Administration marketing approval in October 2017 for treating central sleep apnea has now shown safety and efficacy out to 18 months of continuous use in 102 patients.

After 18 months of treatment with the Remede System, patients’ outcomes remained stable and patients continued to see the improvements they had experienced after 6 and 12 months of treatment. These improvements included significant average reductions from baseline in apnea-hypopnea index and central apnea index and significant increases in oxygenation and sleep quality, Andrew C. Kao, MD, said at the CHEST annual meeting.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

Rates of postoperative hypocalcemia and recurrent laryngeal nerve (RLN) injury after thyroidectomy varied significantly from hospital to hospital in a recent large study of U.S. hospitals, suggesting to the authors that these measures could be used for quality improvement metrics.

In the study, published Nov. 29 in JAMA Surgery, hospitals with significantly lower rates of hypocalcemia were more likely to conduct postoperative parathyroid hormone level measurement as well as to prescribe vitamin D, calcium supplements, or both. Hospitals with lower RLN injury rates more frequently used energy devices and intraoperative nerve monitoring.

“Causation cannot be proven by this, but the confidence that these practice parameters are important is high,” senior author Bruce Hall, MD, PhD, vice president and chief quality officer at BJC Healthcare, and professor of surgery at Washington University, St. Louis, said in an interview. Dr. Hall is consulting director for the American College of Surgeon’s National Surgical Quality Improvement Program (NSQIP), which provided data for the analysis (JAMA Surg. 2017 Nov 29. doi: 10.1001/jamasurg.2017.4593).

Sebastian Kaulitzki/Fotolia

Rates of postoperative hypocalcemia and recurrent laryngeal nerve (RLN) injury after thyroidectomy varied significantly from hospital to hospital in a recent large study of U.S. hospitals, suggesting to the authors that these measures could be used for quality improvement metrics.

In the study, published Nov. 29 in JAMA Surgery, hospitals with significantly lower rates of hypocalcemia were more likely to conduct postoperative parathyroid hormone level measurement as well as to prescribe vitamin D, calcium supplements, or both. Hospitals with lower RLN injury rates more frequently used energy devices and intraoperative nerve monitoring.

“Causation cannot be proven by this, but the confidence that these practice parameters are important is high,” senior author Bruce Hall, MD, PhD, vice president and chief quality officer at BJC Healthcare, and professor of surgery at Washington University, St. Louis, said in an interview. Dr. Hall is consulting director for the American College of Surgeon’s National Surgical Quality Improvement Program (NSQIP), which provided data for the analysis (JAMA Surg. 2017 Nov 29. doi: 10.1001/jamasurg.2017.4593).

Sebastian Kaulitzki/Fotolia

Rates of postoperative hypocalcemia and recurrent laryngeal nerve (RLN) injury after thyroidectomy varied significantly from hospital to hospital in a recent large study of U.S. hospitals, suggesting to the authors that these measures could be used for quality improvement metrics.

In the study, published Nov. 29 in JAMA Surgery, hospitals with significantly lower rates of hypocalcemia were more likely to conduct postoperative parathyroid hormone level measurement as well as to prescribe vitamin D, calcium supplements, or both. Hospitals with lower RLN injury rates more frequently used energy devices and intraoperative nerve monitoring.

“Causation cannot be proven by this, but the confidence that these practice parameters are important is high,” senior author Bruce Hall, MD, PhD, vice president and chief quality officer at BJC Healthcare, and professor of surgery at Washington University, St. Louis, said in an interview. Dr. Hall is consulting director for the American College of Surgeon’s National Surgical Quality Improvement Program (NSQIP), which provided data for the analysis (JAMA Surg. 2017 Nov 29. doi: 10.1001/jamasurg.2017.4593).

Sebastian Kaulitzki/Fotolia

Dermatology departments in the United States have been facing challenges in recruiting and retaining dermatologists for academic positions. Accordingly, a survey study reported that academic dermatologists were more likely than those in private practice to state that their institutions were recruiting new associates.¹ Several factors could explain this phenomenon. Salary differences between jobs in academic and nonacademic settings may contribute to difficulty in recruiting dermatologists into academia, which is exacerbated by a theoretical shortage of dermatologists, leading to graduates who receive and accept private practice job offers.^1,2 Furthermore, a large survey study reported that challenges unique to academic dermatologists include longer patient wait times in addition to responsibilities such as research, hospital consultations, medical writing, and teaching. These patterns raise concerns for the future of teaching institutions because academic dermatologists not only train future physicians but also conduct clinical and basic science research necessary to advance the field and improve patient care.² Thus, it is important to evaluate the factors that affect career decisions in dermatology and to determine if these factors can be addressed. We hypothesized that student loan burden influences career plans in dermatology and that physicians are not fully educated on loan repayment options. The aims of this preliminary study were to explore the influence of student loan burden on career plans in dermatology and to determine if the Public Service Loan Forgiveness (PSLF) program could potentially encourage more dermatologists to consider academic careers.

Methods

The study aimed to investigate the factors that influence career decisions in dermatology and to assess attitudes toward the PSLF program as an option for student loan repayment. The target population included dermatology residents and attending physicians in the United States. Survey questions were adapted from a previously published study³ and were modified based on feedback from reviewers in the University of California (UC) Irvine department of dermatology. The survey was voluntary and did not collect identifying information. This study was granted exemption from oversight by the UC Irvine institutional review board.

Recruitment materials informed potential participants of the nature of the study and provided a hyperlink to the electronic survey. The UC Irvine department of dermatology emailed US dermatology residency program coordinators, requesting that they forward this study to residents and attending physicians in their programs. The survey also was distributed by one of the investigators (E.S.) on a social networking website for dermatologists. Data were collected from June 2015 to October 2015. A χ² analysis was conducted using SAS statistical software, and P<.05 was considered statistically significant.

Results

Demographics
The survey had 70 respondents including residents (56 [80.0%]) and attending physicians (14 [20.0%]). The mean age (SD) of the respondents was 32.4 (6.1) years, with 31 (44.3%) men and 39 (55.7%) women. The majority were married (38 [54.3%]) and did not have children (48 [68.6%]). Most respondents reported an annual household income of $200,000 or less (55 [78.6%]) and perceived a comfortable annual household income as greater than $200,000 (59 [84.3%])(Table 1).

Financing Medical Education
Most respondents currently had $200,000 or less in student loan debt (40 [57.1%]) and financed more than half of their medical education with student loans (53 [75.7%]). A large majority (61 [87.1%]) indicated that some portion of their medical education was funded by student loans. Other means of financing education included family assistance (29 [40.8%]), scholarships (26 [36.6%]), personal savings (18 [25.3%]), and military benefits (1 [1.4%]); 18.3% (n=13) of respondents did not accrue any educational debt. Respondents endorsed several plans for loan repayment including government-sponsored programs (34 [47.9%]), refinancing with a private company (13 [18.3%]), and the PSLF (1 [1.4%]); 12.7% (n=9) of respondents were uncertain how they were going to repay their student loans.

Career Goals in Dermatology and the Influence of Student Loans
Respondents were asked to specify their career plans before versus after starting dermatology residency training (ie, current career plan). Prior to starting residency, 36 (51.4%) and 34 (48.6%) respondents indicated they were interested in private practice and academia, respectively. After starting residency, the number of respondents interested in private practice increased to 45 (64.3%), and the number of respondents interested in academia decreased to 25 (35.7%). Fifteen (21.4%) respondents changed career trajectories from academia to private practice, 6 (8.6%) changed from private practice to academia, and 49 (70.0%) did not change career goals.

The majority of respondents (39 [55.7%]) indicated that the amount of their student loan debt did not influence their career goals (Table 2); however, those with more than $200,000 in debt were more likely to state that student loans impacted their career goals compared to those with $200,000 or less in debt (70.0% [21/30] vs 25.0% [10/40]; P<.001).

Comparison of Respondents Interested in Careers in Academia vs Private Practice
There were differences in financial circumstances between respondents interested in academia versus those interested in private practice. Compared to respondents interested in academia, those interested in private practice were more likely to have more than $200,000 in student loan debt (24 [53.3%] vs 6 [24.0%]; P<.05), have more than half of their education paid with student loans (38 [84.4%] vs 15 [60.0%]; P<.05), and state that student debt affected their career goals (28 [62.2%] vs 3 [12.0%]; P<.001)(Table 3). Demographic characteristics including gender, marital status, parental status, and current annual household income were not associated with a specific career goal.

Subgroup analysis was performed on respondents who were initially interested in academic careers but subsequently decided to pursue private practice (n=15). Compared to those who remained interested in academia, those who changed career plans from academia to private practice were more likely to have more than $200,000 in student debt (76.9% [10/13] vs 23.1% [3/13]; P<.001) and were more likely to state that loans affected their career goals (86.7% [13/15] vs 13.3% [2/15]; P<.001).

Residency program experience also may influence career trajectory. The majority (n=41 [58.6%]) of respondents indicated that their residency program experience affected their dermatology career goals. Of those, 41.7% and 58.5% stated that their residency program experiences dissuaded and persuaded them into academic positions, respectively. Those interested in academic dermatology were more likely to state that their residency program experience influenced their career goals (80.0% [20/25] vs 46.7% [21/45]; P<.05). Furthermore, those interested in academic positions responded with higher overall residency program satisfaction ratings on a scale of 1 to 10 (1 indicated the lowest satisfaction) than those interested in private practice, but the difference was not significant (mean [SD] score, 8.2 [2.3] vs 7.2 [1.9]; P=.07).

Respondents were asked to rate their interest in the following dermatology-related professional interests on a scale of 1 to 5 (1 indicated the least enjoyment): medical dermatology, dermatologic surgery, dermatopathology, cosmetics, and lasers. Those interested in private practice versus those interested in academic dermatology found more enjoyment in dermatologic surgery (mean [SD] score, 4.0 [0.8] vs 3.4 [1.3]; P<.05), cosmetics (3.4 [1.2] vs 2.6 [1.4]; P<.05), and lasers (3.7 [1.0] vs 2.8 [1.2]; P<.05)(Table 4).

Respondents also were asked to select primary motivating factors for their career goals (ie, academia or private practice) and to indicate reasons for not choosing the alternative. The majority of those pursuing academia were motivated by opportunities to collaborate with colleagues (23 [92.0%]), teach and mentor (20 [80%]), and manage complex cases (17 [68.0%]). Most of the respondents who were pursing private practice were motivated by focus on patient care and clinician duties (36 [80.0%]), flexible work hours (35 [77.8%]), higher income (33 [73.3%]), and location flexibility (29 [64.4%]). Among those interested in academic dermatology, the top factors for disinterest in private practice were running a business (9 [36.0%]) and high patient turnover (9 [36.0%]). Most of those interested in private practice indicated that they were not interested in an academic position because of lower income (31 [68.9%]) and research duties (31 [68.9%])(Table 5).

Awareness of and Attitudes Toward the PSLF Program
The majority of respondents were aware of PSLF (53 [75.7%]); however, only 1 respondent endorsed current plans to use PSLF for loan repayment. Respondents were asked how likely they would be to pursue an academic position if given the option to have their student loans forgiven by the PSLF program. Overall, 44.6% (n=25) of respondents indicated that this option would have no effect or would unlikely convince them to pursue an academic position, and 55.4% (n=31) of respondents indicated that they were somewhat likely, likely, or very likely to pursue academia if PSLF was an option. Of those who stated that they would consider enrolling in PSLF, 64.5% (20/31) of individuals were pursuing careers in private practice. Neither current student loan burden nor career goal was associated with likelihood of enrolling in the PSLF.

Comment

In 2015, 76% of medical school graduates in the United States accrued educational debt, with an average of $189,165, a number that has continued to increase over the years.⁴ In addition to the increasing cost of medical education, higher interest rates on federal student loans contribute to debt burden. Over the last 2 decades, some research has posited that debt may influence medical specialty selection, with most studies focusing on primary care.^5-9 However, there is limited information on the effect of student loan debt on career decisions within dermatology.

The results of our study suggest that financial factors including income and amount of educational debt may influence career decisions in dermatology. There is a known income gap between academic and nonacademic settings. According to the Association of American Medical Colleges, the median salaries for an assistant professor and associate/full professor in dermatology are $266,000 and $331,000, respectively.¹⁰ In contrast, for dermatologists in private clinical practice, the overall median salary is more than $450,000. These salary differences may impact career plans, as 73.3% (33/45) of survey respondents in our study who were interested in private practice stated that higher income was one of the primary motivating factors behind their career goals. Student loan burden also may impact career decisions in dermatology. Compared to those with lower student loan debt (≤$200,000), respondents with higher student loan debt (>$200,000) showed greater interest in pursuing positions in private practice and were more likely to change career goals from academia to private practice after starting residency. Thus, academic institutions are potentially losing physicians who are interested in academic careers but ultimately decide against it, at least partially due to high student loan debt.

The PSLF can potentially address this issue and be used as a recruiting tool for dermatology positions in academia. Under PSLF, borrowers can have the remainder of their loan balances forgiven after making 120 monthly payments while employed full time by public service employers, including some academic medical institutions. In our study, a large majority of respondents indicated that they are aware of the PSLF, and more than half said they would consider pursuing positions in academia if their loans could be forgiven through the program; however, when asked about plans for loan repayment, only 1 respondent endorsed current plans to enroll in PSLF. Thus, despite high interest in PSLF among the survey respondents, few had actual plans to use the service, suggesting that perhaps dermatologists are not provided enough information about PSLF to motivate enrollment. In the same way, almost a quarter of respondents were not familiar with the PSLF as a repayment option, further signifying that distribution of information about financial planning may be inadequate. If student loan burden is a notable factor in career decisions in dermatology, it is important that academic institutions provide sufficient information about repayment to encourage informed decisions. As such, it is possible that educating physicians about options such as PSLF can potentially recruit more dermatologists to academic positions.

Aside from financial reasons, residency program experience and differences in practices in academic and nonacademic settings may impact career trajectories. The majority of respondents stated their residency program experience influenced their career decisions; however, the majority of respondents did not change their minds about career goals since starting residency, suggesting that residency program experience may reinforce but not necessarily alter these choices. Interests in specific focuses within dermatology also may influence career decisions. This study suggests that those pursuing private practice positions are more interested in dermatologic surgery, lasers, and cosmetics. Roles in research, mentoring, and patient care differ between academic and nonacademic settings and also may be influential in career decisions in dermatology, mirroring the implications of other studies that posited that career decisions within medicine are complex and involve multiple factors.¹¹

In this study, we did not find an association between gender and career plans in dermatology. In 2013, more than 60% of dermatology resident physicians were female.¹² However, a recent study suggested that women face challenges in academic dermatology, including a downtrend in the number of female investigators with grants from the National Institutes of Health.¹³Taken together, female dermatologists, who currently represent the majority of resident physicians training in dermatology, may face unique challenges in academia, further highlighting the potential difficulties with recruitment of dermatologists by academic institutions in the future.

This preliminary study has several limitations. First, the small sample size limited generalizability to all dermatologists. Second, responder bias was possible, as those who have stronger opinions about this topic may have been more inclined to participate in this voluntary survey. Future studies with larger sample sizes are needed to further explore the factors that influence career decisions within dermatology and to determine if there are additional means to increase recruitment into academia.

Conclusion

It is recognized that there are challenges in recruiting dermatologists into academic positions. This study suggests that student loan burden influences career decisions in dermatology. Dermatologists may not be fully educated on options for student loan repayment. With increased awareness, the PSLF can potentially be used as a recruitment tool for positions in academic dermatology.

Dermatology departments in the United States have been facing challenges in recruiting and retaining dermatologists for academic positions. Accordingly, a survey study reported that academic dermatologists were more likely than those in private practice to state that their institutions were recruiting new associates.¹ Several factors could explain this phenomenon. Salary differences between jobs in academic and nonacademic settings may contribute to difficulty in recruiting dermatologists into academia, which is exacerbated by a theoretical shortage of dermatologists, leading to graduates who receive and accept private practice job offers.^1,2 Furthermore, a large survey study reported that challenges unique to academic dermatologists include longer patient wait times in addition to responsibilities such as research, hospital consultations, medical writing, and teaching. These patterns raise concerns for the future of teaching institutions because academic dermatologists not only train future physicians but also conduct clinical and basic science research necessary to advance the field and improve patient care.² Thus, it is important to evaluate the factors that affect career decisions in dermatology and to determine if these factors can be addressed. We hypothesized that student loan burden influences career plans in dermatology and that physicians are not fully educated on loan repayment options. The aims of this preliminary study were to explore the influence of student loan burden on career plans in dermatology and to determine if the Public Service Loan Forgiveness (PSLF) program could potentially encourage more dermatologists to consider academic careers.

Methods

The study aimed to investigate the factors that influence career decisions in dermatology and to assess attitudes toward the PSLF program as an option for student loan repayment. The target population included dermatology residents and attending physicians in the United States. Survey questions were adapted from a previously published study³ and were modified based on feedback from reviewers in the University of California (UC) Irvine department of dermatology. The survey was voluntary and did not collect identifying information. This study was granted exemption from oversight by the UC Irvine institutional review board.

Recruitment materials informed potential participants of the nature of the study and provided a hyperlink to the electronic survey. The UC Irvine department of dermatology emailed US dermatology residency program coordinators, requesting that they forward this study to residents and attending physicians in their programs. The survey also was distributed by one of the investigators (E.S.) on a social networking website for dermatologists. Data were collected from June 2015 to October 2015. A χ² analysis was conducted using SAS statistical software, and P<.05 was considered statistically significant.

Results

Demographics
The survey had 70 respondents including residents (56 [80.0%]) and attending physicians (14 [20.0%]). The mean age (SD) of the respondents was 32.4 (6.1) years, with 31 (44.3%) men and 39 (55.7%) women. The majority were married (38 [54.3%]) and did not have children (48 [68.6%]). Most respondents reported an annual household income of $200,000 or less (55 [78.6%]) and perceived a comfortable annual household income as greater than $200,000 (59 [84.3%])(Table 1).

Financing Medical Education
Most respondents currently had $200,000 or less in student loan debt (40 [57.1%]) and financed more than half of their medical education with student loans (53 [75.7%]). A large majority (61 [87.1%]) indicated that some portion of their medical education was funded by student loans. Other means of financing education included family assistance (29 [40.8%]), scholarships (26 [36.6%]), personal savings (18 [25.3%]), and military benefits (1 [1.4%]); 18.3% (n=13) of respondents did not accrue any educational debt. Respondents endorsed several plans for loan repayment including government-sponsored programs (34 [47.9%]), refinancing with a private company (13 [18.3%]), and the PSLF (1 [1.4%]); 12.7% (n=9) of respondents were uncertain how they were going to repay their student loans.

Career Goals in Dermatology and the Influence of Student Loans
Respondents were asked to specify their career plans before versus after starting dermatology residency training (ie, current career plan). Prior to starting residency, 36 (51.4%) and 34 (48.6%) respondents indicated they were interested in private practice and academia, respectively. After starting residency, the number of respondents interested in private practice increased to 45 (64.3%), and the number of respondents interested in academia decreased to 25 (35.7%). Fifteen (21.4%) respondents changed career trajectories from academia to private practice, 6 (8.6%) changed from private practice to academia, and 49 (70.0%) did not change career goals.

The majority of respondents (39 [55.7%]) indicated that the amount of their student loan debt did not influence their career goals (Table 2); however, those with more than $200,000 in debt were more likely to state that student loans impacted their career goals compared to those with $200,000 or less in debt (70.0% [21/30] vs 25.0% [10/40]; P<.001).

Comparison of Respondents Interested in Careers in Academia vs Private Practice
There were differences in financial circumstances between respondents interested in academia versus those interested in private practice. Compared to respondents interested in academia, those interested in private practice were more likely to have more than $200,000 in student loan debt (24 [53.3%] vs 6 [24.0%]; P<.05), have more than half of their education paid with student loans (38 [84.4%] vs 15 [60.0%]; P<.05), and state that student debt affected their career goals (28 [62.2%] vs 3 [12.0%]; P<.001)(Table 3). Demographic characteristics including gender, marital status, parental status, and current annual household income were not associated with a specific career goal.

Subgroup analysis was performed on respondents who were initially interested in academic careers but subsequently decided to pursue private practice (n=15). Compared to those who remained interested in academia, those who changed career plans from academia to private practice were more likely to have more than $200,000 in student debt (76.9% [10/13] vs 23.1% [3/13]; P<.001) and were more likely to state that loans affected their career goals (86.7% [13/15] vs 13.3% [2/15]; P<.001).

Residency program experience also may influence career trajectory. The majority (n=41 [58.6%]) of respondents indicated that their residency program experience affected their dermatology career goals. Of those, 41.7% and 58.5% stated that their residency program experiences dissuaded and persuaded them into academic positions, respectively. Those interested in academic dermatology were more likely to state that their residency program experience influenced their career goals (80.0% [20/25] vs 46.7% [21/45]; P<.05). Furthermore, those interested in academic positions responded with higher overall residency program satisfaction ratings on a scale of 1 to 10 (1 indicated the lowest satisfaction) than those interested in private practice, but the difference was not significant (mean [SD] score, 8.2 [2.3] vs 7.2 [1.9]; P=.07).

Respondents were asked to rate their interest in the following dermatology-related professional interests on a scale of 1 to 5 (1 indicated the least enjoyment): medical dermatology, dermatologic surgery, dermatopathology, cosmetics, and lasers. Those interested in private practice versus those interested in academic dermatology found more enjoyment in dermatologic surgery (mean [SD] score, 4.0 [0.8] vs 3.4 [1.3]; P<.05), cosmetics (3.4 [1.2] vs 2.6 [1.4]; P<.05), and lasers (3.7 [1.0] vs 2.8 [1.2]; P<.05)(Table 4).

Respondents also were asked to select primary motivating factors for their career goals (ie, academia or private practice) and to indicate reasons for not choosing the alternative. The majority of those pursuing academia were motivated by opportunities to collaborate with colleagues (23 [92.0%]), teach and mentor (20 [80%]), and manage complex cases (17 [68.0%]). Most of the respondents who were pursing private practice were motivated by focus on patient care and clinician duties (36 [80.0%]), flexible work hours (35 [77.8%]), higher income (33 [73.3%]), and location flexibility (29 [64.4%]). Among those interested in academic dermatology, the top factors for disinterest in private practice were running a business (9 [36.0%]) and high patient turnover (9 [36.0%]). Most of those interested in private practice indicated that they were not interested in an academic position because of lower income (31 [68.9%]) and research duties (31 [68.9%])(Table 5).

Awareness of and Attitudes Toward the PSLF Program
The majority of respondents were aware of PSLF (53 [75.7%]); however, only 1 respondent endorsed current plans to use PSLF for loan repayment. Respondents were asked how likely they would be to pursue an academic position if given the option to have their student loans forgiven by the PSLF program. Overall, 44.6% (n=25) of respondents indicated that this option would have no effect or would unlikely convince them to pursue an academic position, and 55.4% (n=31) of respondents indicated that they were somewhat likely, likely, or very likely to pursue academia if PSLF was an option. Of those who stated that they would consider enrolling in PSLF, 64.5% (20/31) of individuals were pursuing careers in private practice. Neither current student loan burden nor career goal was associated with likelihood of enrolling in the PSLF.

Comment

In 2015, 76% of medical school graduates in the United States accrued educational debt, with an average of $189,165, a number that has continued to increase over the years.⁴ In addition to the increasing cost of medical education, higher interest rates on federal student loans contribute to debt burden. Over the last 2 decades, some research has posited that debt may influence medical specialty selection, with most studies focusing on primary care.^5-9 However, there is limited information on the effect of student loan debt on career decisions within dermatology.

The results of our study suggest that financial factors including income and amount of educational debt may influence career decisions in dermatology. There is a known income gap between academic and nonacademic settings. According to the Association of American Medical Colleges, the median salaries for an assistant professor and associate/full professor in dermatology are $266,000 and $331,000, respectively.¹⁰ In contrast, for dermatologists in private clinical practice, the overall median salary is more than $450,000. These salary differences may impact career plans, as 73.3% (33/45) of survey respondents in our study who were interested in private practice stated that higher income was one of the primary motivating factors behind their career goals. Student loan burden also may impact career decisions in dermatology. Compared to those with lower student loan debt (≤$200,000), respondents with higher student loan debt (>$200,000) showed greater interest in pursuing positions in private practice and were more likely to change career goals from academia to private practice after starting residency. Thus, academic institutions are potentially losing physicians who are interested in academic careers but ultimately decide against it, at least partially due to high student loan debt.

The PSLF can potentially address this issue and be used as a recruiting tool for dermatology positions in academia. Under PSLF, borrowers can have the remainder of their loan balances forgiven after making 120 monthly payments while employed full time by public service employers, including some academic medical institutions. In our study, a large majority of respondents indicated that they are aware of the PSLF, and more than half said they would consider pursuing positions in academia if their loans could be forgiven through the program; however, when asked about plans for loan repayment, only 1 respondent endorsed current plans to enroll in PSLF. Thus, despite high interest in PSLF among the survey respondents, few had actual plans to use the service, suggesting that perhaps dermatologists are not provided enough information about PSLF to motivate enrollment. In the same way, almost a quarter of respondents were not familiar with the PSLF as a repayment option, further signifying that distribution of information about financial planning may be inadequate. If student loan burden is a notable factor in career decisions in dermatology, it is important that academic institutions provide sufficient information about repayment to encourage informed decisions. As such, it is possible that educating physicians about options such as PSLF can potentially recruit more dermatologists to academic positions.

Aside from financial reasons, residency program experience and differences in practices in academic and nonacademic settings may impact career trajectories. The majority of respondents stated their residency program experience influenced their career decisions; however, the majority of respondents did not change their minds about career goals since starting residency, suggesting that residency program experience may reinforce but not necessarily alter these choices. Interests in specific focuses within dermatology also may influence career decisions. This study suggests that those pursuing private practice positions are more interested in dermatologic surgery, lasers, and cosmetics. Roles in research, mentoring, and patient care differ between academic and nonacademic settings and also may be influential in career decisions in dermatology, mirroring the implications of other studies that posited that career decisions within medicine are complex and involve multiple factors.¹¹

In this study, we did not find an association between gender and career plans in dermatology. In 2013, more than 60% of dermatology resident physicians were female.¹² However, a recent study suggested that women face challenges in academic dermatology, including a downtrend in the number of female investigators with grants from the National Institutes of Health.¹³Taken together, female dermatologists, who currently represent the majority of resident physicians training in dermatology, may face unique challenges in academia, further highlighting the potential difficulties with recruitment of dermatologists by academic institutions in the future.

This preliminary study has several limitations. First, the small sample size limited generalizability to all dermatologists. Second, responder bias was possible, as those who have stronger opinions about this topic may have been more inclined to participate in this voluntary survey. Future studies with larger sample sizes are needed to further explore the factors that influence career decisions within dermatology and to determine if there are additional means to increase recruitment into academia.

Conclusion

It is recognized that there are challenges in recruiting dermatologists into academic positions. This study suggests that student loan burden influences career decisions in dermatology. Dermatologists may not be fully educated on options for student loan repayment. With increased awareness, the PSLF can potentially be used as a recruitment tool for positions in academic dermatology.

Dermatology departments in the United States have been facing challenges in recruiting and retaining dermatologists for academic positions. Accordingly, a survey study reported that academic dermatologists were more likely than those in private practice to state that their institutions were recruiting new associates.¹ Several factors could explain this phenomenon. Salary differences between jobs in academic and nonacademic settings may contribute to difficulty in recruiting dermatologists into academia, which is exacerbated by a theoretical shortage of dermatologists, leading to graduates who receive and accept private practice job offers.^1,2 Furthermore, a large survey study reported that challenges unique to academic dermatologists include longer patient wait times in addition to responsibilities such as research, hospital consultations, medical writing, and teaching. These patterns raise concerns for the future of teaching institutions because academic dermatologists not only train future physicians but also conduct clinical and basic science research necessary to advance the field and improve patient care.² Thus, it is important to evaluate the factors that affect career decisions in dermatology and to determine if these factors can be addressed. We hypothesized that student loan burden influences career plans in dermatology and that physicians are not fully educated on loan repayment options. The aims of this preliminary study were to explore the influence of student loan burden on career plans in dermatology and to determine if the Public Service Loan Forgiveness (PSLF) program could potentially encourage more dermatologists to consider academic careers.

Methods

The study aimed to investigate the factors that influence career decisions in dermatology and to assess attitudes toward the PSLF program as an option for student loan repayment. The target population included dermatology residents and attending physicians in the United States. Survey questions were adapted from a previously published study³ and were modified based on feedback from reviewers in the University of California (UC) Irvine department of dermatology. The survey was voluntary and did not collect identifying information. This study was granted exemption from oversight by the UC Irvine institutional review board.

Recruitment materials informed potential participants of the nature of the study and provided a hyperlink to the electronic survey. The UC Irvine department of dermatology emailed US dermatology residency program coordinators, requesting that they forward this study to residents and attending physicians in their programs. The survey also was distributed by one of the investigators (E.S.) on a social networking website for dermatologists. Data were collected from June 2015 to October 2015. A χ² analysis was conducted using SAS statistical software, and P<.05 was considered statistically significant.

Results

Demographics
The survey had 70 respondents including residents (56 [80.0%]) and attending physicians (14 [20.0%]). The mean age (SD) of the respondents was 32.4 (6.1) years, with 31 (44.3%) men and 39 (55.7%) women. The majority were married (38 [54.3%]) and did not have children (48 [68.6%]). Most respondents reported an annual household income of $200,000 or less (55 [78.6%]) and perceived a comfortable annual household income as greater than $200,000 (59 [84.3%])(Table 1).

Financing Medical Education
Most respondents currently had $200,000 or less in student loan debt (40 [57.1%]) and financed more than half of their medical education with student loans (53 [75.7%]). A large majority (61 [87.1%]) indicated that some portion of their medical education was funded by student loans. Other means of financing education included family assistance (29 [40.8%]), scholarships (26 [36.6%]), personal savings (18 [25.3%]), and military benefits (1 [1.4%]); 18.3% (n=13) of respondents did not accrue any educational debt. Respondents endorsed several plans for loan repayment including government-sponsored programs (34 [47.9%]), refinancing with a private company (13 [18.3%]), and the PSLF (1 [1.4%]); 12.7% (n=9) of respondents were uncertain how they were going to repay their student loans.

Career Goals in Dermatology and the Influence of Student Loans
Respondents were asked to specify their career plans before versus after starting dermatology residency training (ie, current career plan). Prior to starting residency, 36 (51.4%) and 34 (48.6%) respondents indicated they were interested in private practice and academia, respectively. After starting residency, the number of respondents interested in private practice increased to 45 (64.3%), and the number of respondents interested in academia decreased to 25 (35.7%). Fifteen (21.4%) respondents changed career trajectories from academia to private practice, 6 (8.6%) changed from private practice to academia, and 49 (70.0%) did not change career goals.

The majority of respondents (39 [55.7%]) indicated that the amount of their student loan debt did not influence their career goals (Table 2); however, those with more than $200,000 in debt were more likely to state that student loans impacted their career goals compared to those with $200,000 or less in debt (70.0% [21/30] vs 25.0% [10/40]; P<.001).

Comparison of Respondents Interested in Careers in Academia vs Private Practice
There were differences in financial circumstances between respondents interested in academia versus those interested in private practice. Compared to respondents interested in academia, those interested in private practice were more likely to have more than $200,000 in student loan debt (24 [53.3%] vs 6 [24.0%]; P<.05), have more than half of their education paid with student loans (38 [84.4%] vs 15 [60.0%]; P<.05), and state that student debt affected their career goals (28 [62.2%] vs 3 [12.0%]; P<.001)(Table 3). Demographic characteristics including gender, marital status, parental status, and current annual household income were not associated with a specific career goal.

Subgroup analysis was performed on respondents who were initially interested in academic careers but subsequently decided to pursue private practice (n=15). Compared to those who remained interested in academia, those who changed career plans from academia to private practice were more likely to have more than $200,000 in student debt (76.9% [10/13] vs 23.1% [3/13]; P<.001) and were more likely to state that loans affected their career goals (86.7% [13/15] vs 13.3% [2/15]; P<.001).

Residency program experience also may influence career trajectory. The majority (n=41 [58.6%]) of respondents indicated that their residency program experience affected their dermatology career goals. Of those, 41.7% and 58.5% stated that their residency program experiences dissuaded and persuaded them into academic positions, respectively. Those interested in academic dermatology were more likely to state that their residency program experience influenced their career goals (80.0% [20/25] vs 46.7% [21/45]; P<.05). Furthermore, those interested in academic positions responded with higher overall residency program satisfaction ratings on a scale of 1 to 10 (1 indicated the lowest satisfaction) than those interested in private practice, but the difference was not significant (mean [SD] score, 8.2 [2.3] vs 7.2 [1.9]; P=.07).

Respondents were asked to rate their interest in the following dermatology-related professional interests on a scale of 1 to 5 (1 indicated the least enjoyment): medical dermatology, dermatologic surgery, dermatopathology, cosmetics, and lasers. Those interested in private practice versus those interested in academic dermatology found more enjoyment in dermatologic surgery (mean [SD] score, 4.0 [0.8] vs 3.4 [1.3]; P<.05), cosmetics (3.4 [1.2] vs 2.6 [1.4]; P<.05), and lasers (3.7 [1.0] vs 2.8 [1.2]; P<.05)(Table 4).

Respondents also were asked to select primary motivating factors for their career goals (ie, academia or private practice) and to indicate reasons for not choosing the alternative. The majority of those pursuing academia were motivated by opportunities to collaborate with colleagues (23 [92.0%]), teach and mentor (20 [80%]), and manage complex cases (17 [68.0%]). Most of the respondents who were pursing private practice were motivated by focus on patient care and clinician duties (36 [80.0%]), flexible work hours (35 [77.8%]), higher income (33 [73.3%]), and location flexibility (29 [64.4%]). Among those interested in academic dermatology, the top factors for disinterest in private practice were running a business (9 [36.0%]) and high patient turnover (9 [36.0%]). Most of those interested in private practice indicated that they were not interested in an academic position because of lower income (31 [68.9%]) and research duties (31 [68.9%])(Table 5).

Awareness of and Attitudes Toward the PSLF Program
The majority of respondents were aware of PSLF (53 [75.7%]); however, only 1 respondent endorsed current plans to use PSLF for loan repayment. Respondents were asked how likely they would be to pursue an academic position if given the option to have their student loans forgiven by the PSLF program. Overall, 44.6% (n=25) of respondents indicated that this option would have no effect or would unlikely convince them to pursue an academic position, and 55.4% (n=31) of respondents indicated that they were somewhat likely, likely, or very likely to pursue academia if PSLF was an option. Of those who stated that they would consider enrolling in PSLF, 64.5% (20/31) of individuals were pursuing careers in private practice. Neither current student loan burden nor career goal was associated with likelihood of enrolling in the PSLF.

Comment

In 2015, 76% of medical school graduates in the United States accrued educational debt, with an average of $189,165, a number that has continued to increase over the years.⁴ In addition to the increasing cost of medical education, higher interest rates on federal student loans contribute to debt burden. Over the last 2 decades, some research has posited that debt may influence medical specialty selection, with most studies focusing on primary care.^5-9 However, there is limited information on the effect of student loan debt on career decisions within dermatology.

The results of our study suggest that financial factors including income and amount of educational debt may influence career decisions in dermatology. There is a known income gap between academic and nonacademic settings. According to the Association of American Medical Colleges, the median salaries for an assistant professor and associate/full professor in dermatology are $266,000 and $331,000, respectively.¹⁰ In contrast, for dermatologists in private clinical practice, the overall median salary is more than $450,000. These salary differences may impact career plans, as 73.3% (33/45) of survey respondents in our study who were interested in private practice stated that higher income was one of the primary motivating factors behind their career goals. Student loan burden also may impact career decisions in dermatology. Compared to those with lower student loan debt (≤$200,000), respondents with higher student loan debt (>$200,000) showed greater interest in pursuing positions in private practice and were more likely to change career goals from academia to private practice after starting residency. Thus, academic institutions are potentially losing physicians who are interested in academic careers but ultimately decide against it, at least partially due to high student loan debt.

The PSLF can potentially address this issue and be used as a recruiting tool for dermatology positions in academia. Under PSLF, borrowers can have the remainder of their loan balances forgiven after making 120 monthly payments while employed full time by public service employers, including some academic medical institutions. In our study, a large majority of respondents indicated that they are aware of the PSLF, and more than half said they would consider pursuing positions in academia if their loans could be forgiven through the program; however, when asked about plans for loan repayment, only 1 respondent endorsed current plans to enroll in PSLF. Thus, despite high interest in PSLF among the survey respondents, few had actual plans to use the service, suggesting that perhaps dermatologists are not provided enough information about PSLF to motivate enrollment. In the same way, almost a quarter of respondents were not familiar with the PSLF as a repayment option, further signifying that distribution of information about financial planning may be inadequate. If student loan burden is a notable factor in career decisions in dermatology, it is important that academic institutions provide sufficient information about repayment to encourage informed decisions. As such, it is possible that educating physicians about options such as PSLF can potentially recruit more dermatologists to academic positions.

Aside from financial reasons, residency program experience and differences in practices in academic and nonacademic settings may impact career trajectories. The majority of respondents stated their residency program experience influenced their career decisions; however, the majority of respondents did not change their minds about career goals since starting residency, suggesting that residency program experience may reinforce but not necessarily alter these choices. Interests in specific focuses within dermatology also may influence career decisions. This study suggests that those pursuing private practice positions are more interested in dermatologic surgery, lasers, and cosmetics. Roles in research, mentoring, and patient care differ between academic and nonacademic settings and also may be influential in career decisions in dermatology, mirroring the implications of other studies that posited that career decisions within medicine are complex and involve multiple factors.¹¹

In this study, we did not find an association between gender and career plans in dermatology. In 2013, more than 60% of dermatology resident physicians were female.¹² However, a recent study suggested that women face challenges in academic dermatology, including a downtrend in the number of female investigators with grants from the National Institutes of Health.¹³Taken together, female dermatologists, who currently represent the majority of resident physicians training in dermatology, may face unique challenges in academia, further highlighting the potential difficulties with recruitment of dermatologists by academic institutions in the future.

This preliminary study has several limitations. First, the small sample size limited generalizability to all dermatologists. Second, responder bias was possible, as those who have stronger opinions about this topic may have been more inclined to participate in this voluntary survey. Future studies with larger sample sizes are needed to further explore the factors that influence career decisions within dermatology and to determine if there are additional means to increase recruitment into academia.

Conclusion

It is recognized that there are challenges in recruiting dermatologists into academic positions. This study suggests that student loan burden influences career decisions in dermatology. Dermatologists may not be fully educated on options for student loan repayment. With increased awareness, the PSLF can potentially be used as a recruitment tool for positions in academic dermatology.

Multinucleate cell angiohistiocytoma (MCAH) is a rare benign, soft-tissue tumor first described in 1985 by Smith and Jones¹ that presents clinically as erythematous to violaceous papules most commonly affecting females on the dorsal aspect of the hands and face.² Multinucleate cell angiohistiocytoma is histologically characterized by vascular and histiocytic proliferations with dermal fibrosis. Few cases have been reported of lesions affecting the lower extremities. We report a case of MCAH affecting the legs.

Case Report

An 83-year-old white man with a history of basal cell carcinoma presented for evaluation of grouped, well-circumscribed, soft, red-violet, painless papules on the right anterior thigh that had been present for 8 months (Figure 1A). A review of symptoms was negative for immunologic, respiratory, and hematologic changes. The patient’s medical history also was remarkable for prostate cancer treated with radiation 18 years prior as well as right hip and left knee implants. The initial clinical impression was Kaposi sarcoma or a granulomatous disorder.

Histopathologic evaluation of a deep shave biopsy initially determined the lesion to be scar tissue without other pathologic findings. The patient returned to the clinic 12 months later for a complete skin examination given his history of skin cancer. Compared to clinical photographs taken a year prior, new violaceous papules were noted on the right thigh (Figure 1B) and left calf. Furthermore, there was no recurrence of the lesion at the prior biopsy site. Shave biopsies of the papules on the right thigh and left calf demonstrated similar histologic findings to each other. There was a mild increase in the number of small blood vessels in the superficial dermis (Figure 2A). A mild perivascular lymphocytic infiltrate surrounded some of these blood vessels. The endothelial cells had small nuclei with no evidence of nuclear pleomorphism. Careful examination of the interstitial dermis revealed scattered multinucleate cells with angulated cytoplasm (Figure 2B). Immunostaining for CD31 and human herpesvirus 8 were negative, excluding an infiltrative vascular tumor and Kaposi sarcoma, respectively. The diagnosis of MCAH was made based on the histopathologic findings.

At 1-year follow-up, the condition was stable with no gross changes in the lesions based on prior photographs. Once again, there was no recurrence of the excised lesions at both biopsy sites.

Comment

Presentation
A systematic review of published reports determined that 79% of MCAH cases occur in females, with an average age of onset of 50.1 years.² However, MCAH likely is underreported due to the overall lack of knowledge regarding this condition by physicians and pathologists. The hands and face are the most commonly affected areas, though other sites of involvement have been reported, including the lower extremities,^3,4 oral mucosa and upper lip,^5,6 and trunk,^7,8 as well as generalized distribution.^9-12 Additionally, 1 case presented as a single plaque on the trunk rather than having papular or nodular morphology.⁸ Multinucleate cell angiohistiocytoma lesions generally are asymptomatic, though pruritus may be present.¹³ The condition is regarded as benign, though a minority of cases have exhibited spontaneous resolution.^14-16

Histopathology
Multinucleate cell angiohistiocytoma histology demonstrates full-thickness dermal microvessel proliferation and fibrosis with characteristic multinucleate giant cells.^2,3 Vascular endothelial cells stained positive for CD68 in 60% of cases² as well as the normal endothelial markers (ie, factor VIII, CD31, CD34). The multinucleate giant cells exhibit immunoreactivity for macrophage/histiocytic markers factor XIIIa and CD68.

Etiology
The pathogenesis of MCAH is not yet fully understood, but it is considered to be a benign vascular or fibrohistiocytic neoplasm.¹⁷ Calderaro et al¹⁸ described a series of 8 patients who developed MCAH either within a cutaneous neoplastic process or in conjunction with various cutaneous reactive conditions, including hidradenitis suppurativa and chronic radiation dermatitis, as well as overlying a bone prosthesis placed due to degenerative arthritis. These cases suggest that MCAH, or possibly a subset of the disease, is a reactive process. Suggested inciting events include cancer with stromal inflammatory reaction, chronic inflammation (as seen in hidradenitis suppurativa), chronic radiation dermatitis, scarring, and vascular injury.¹⁸ Retrospective immunohistochemical evaluation of a series of MCAH cases demonstrated intralesional spindle cells to strongly express estrogen receptor alpha and factor XIIIa. Additionally, these cells sparsely expressed progesterone receptor and demonstrated no vascular endothelial growth factor immunoreactivity.¹⁹ This immunohistochemical profile supports MCAH as a distinct entity from dermatofibromas. These findings also suggest a role of hormone signaling, namely estrogen receptor alpha, in MCAH tumor biology and may offer an explanation for the predilection of MCAH in females. Furthermore, estrogen receptor positivity offers a possible mechanism for the highly vascular nature of the lesions, considering the angiogenic properties of estrogen signaling.²⁰ In a systematic review of 142 published cases of MCAH, CD68 positivity on multinucleate cells in MCAH lesions suggested a fibrohistiocytic origin.² However, a number of these cases exhibited CD34 positivity, thus a macrophage origin may not be excluded.

Differential Diagnosis
The differential diagnosis for MCAH includes Kaposi sarcoma clinically and dermatofibroma and fibrous papules histologically. Sass et al²¹ determined the in vitro behavior of cultured MCAH cells to contrast markedly with Kaposi sarcoma–derived cells. Although Kaposi sarcoma–derived cells exhibited invasive behavior, cells isolated from MCAH lesions were less elongated and were unable to traverse basement membranes.

Treatment
Surgical excision or cryotherapy appear to be definitive treatments of MCAH; however, a number of cases have reported light and laser modalities as successful alternatives to excision. One case of MCAH affecting the face was treated with pulsed dye laser monotherapy.²² This modality allowed selective coagulation of the vascular structures in MCAH. At 8-month follow-up, the initial lesion was noted to be completely cleared, though similar lesions had recently appeared elsewhere on the face.²² Another case of MCAH affecting the leg was treated with pulsed dye laser and both topical and intralesional corticosteroid combination therapy. In this case, the lesion failed to respond to treatment, which may suggest that facial localization could influence response in pulsed dye laser treatment.³

Intense pulsed light also has been reported as a definitive treatment in 2 cases.^2,13 Slight erythema and transient pruritus have been reported immediately following treatment. In this case, complete resolution with only residual hyperpigmentation was reported at 2-month follow-up, with no recurrence during 12 months of follow-up.¹³

Argon laser therapy has been used in 2 cases. After a single session, lesions were no longer palpable, with no scarring noted at 8 weeks follow-up.²³ Lastly, 2 cases of MCAH have been successfully treated with the CO₂ laser, with no relapse noted at 2.5- or 5-month follow-up, respectively.²⁴

Conclusion

Multinucleate cell angiohistiocytoma is a rare and likely underdiagnosed dermatologic condition that is believed to be a reactive process. Characteristic histology of MCAH demonstrates microvascular proliferations of the dermis with multinucleate giant cells amidst a fibrous background. Although surgical excision is curative, there are reports in which laser and light therapies were used to effectively treat MCAH.

Multinucleate cell angiohistiocytoma (MCAH) is a rare benign, soft-tissue tumor first described in 1985 by Smith and Jones¹ that presents clinically as erythematous to violaceous papules most commonly affecting females on the dorsal aspect of the hands and face.² Multinucleate cell angiohistiocytoma is histologically characterized by vascular and histiocytic proliferations with dermal fibrosis. Few cases have been reported of lesions affecting the lower extremities. We report a case of MCAH affecting the legs.

Case Report

An 83-year-old white man with a history of basal cell carcinoma presented for evaluation of grouped, well-circumscribed, soft, red-violet, painless papules on the right anterior thigh that had been present for 8 months (Figure 1A). A review of symptoms was negative for immunologic, respiratory, and hematologic changes. The patient’s medical history also was remarkable for prostate cancer treated with radiation 18 years prior as well as right hip and left knee implants. The initial clinical impression was Kaposi sarcoma or a granulomatous disorder.

Histopathologic evaluation of a deep shave biopsy initially determined the lesion to be scar tissue without other pathologic findings. The patient returned to the clinic 12 months later for a complete skin examination given his history of skin cancer. Compared to clinical photographs taken a year prior, new violaceous papules were noted on the right thigh (Figure 1B) and left calf. Furthermore, there was no recurrence of the lesion at the prior biopsy site. Shave biopsies of the papules on the right thigh and left calf demonstrated similar histologic findings to each other. There was a mild increase in the number of small blood vessels in the superficial dermis (Figure 2A). A mild perivascular lymphocytic infiltrate surrounded some of these blood vessels. The endothelial cells had small nuclei with no evidence of nuclear pleomorphism. Careful examination of the interstitial dermis revealed scattered multinucleate cells with angulated cytoplasm (Figure 2B). Immunostaining for CD31 and human herpesvirus 8 were negative, excluding an infiltrative vascular tumor and Kaposi sarcoma, respectively. The diagnosis of MCAH was made based on the histopathologic findings.

At 1-year follow-up, the condition was stable with no gross changes in the lesions based on prior photographs. Once again, there was no recurrence of the excised lesions at both biopsy sites.

Comment

Presentation
A systematic review of published reports determined that 79% of MCAH cases occur in females, with an average age of onset of 50.1 years.² However, MCAH likely is underreported due to the overall lack of knowledge regarding this condition by physicians and pathologists. The hands and face are the most commonly affected areas, though other sites of involvement have been reported, including the lower extremities,^3,4 oral mucosa and upper lip,^5,6 and trunk,^7,8 as well as generalized distribution.^9-12 Additionally, 1 case presented as a single plaque on the trunk rather than having papular or nodular morphology.⁸ Multinucleate cell angiohistiocytoma lesions generally are asymptomatic, though pruritus may be present.¹³ The condition is regarded as benign, though a minority of cases have exhibited spontaneous resolution.^14-16

Histopathology
Multinucleate cell angiohistiocytoma histology demonstrates full-thickness dermal microvessel proliferation and fibrosis with characteristic multinucleate giant cells.^2,3 Vascular endothelial cells stained positive for CD68 in 60% of cases² as well as the normal endothelial markers (ie, factor VIII, CD31, CD34). The multinucleate giant cells exhibit immunoreactivity for macrophage/histiocytic markers factor XIIIa and CD68.

Etiology
The pathogenesis of MCAH is not yet fully understood, but it is considered to be a benign vascular or fibrohistiocytic neoplasm.¹⁷ Calderaro et al¹⁸ described a series of 8 patients who developed MCAH either within a cutaneous neoplastic process or in conjunction with various cutaneous reactive conditions, including hidradenitis suppurativa and chronic radiation dermatitis, as well as overlying a bone prosthesis placed due to degenerative arthritis. These cases suggest that MCAH, or possibly a subset of the disease, is a reactive process. Suggested inciting events include cancer with stromal inflammatory reaction, chronic inflammation (as seen in hidradenitis suppurativa), chronic radiation dermatitis, scarring, and vascular injury.¹⁸ Retrospective immunohistochemical evaluation of a series of MCAH cases demonstrated intralesional spindle cells to strongly express estrogen receptor alpha and factor XIIIa. Additionally, these cells sparsely expressed progesterone receptor and demonstrated no vascular endothelial growth factor immunoreactivity.¹⁹ This immunohistochemical profile supports MCAH as a distinct entity from dermatofibromas. These findings also suggest a role of hormone signaling, namely estrogen receptor alpha, in MCAH tumor biology and may offer an explanation for the predilection of MCAH in females. Furthermore, estrogen receptor positivity offers a possible mechanism for the highly vascular nature of the lesions, considering the angiogenic properties of estrogen signaling.²⁰ In a systematic review of 142 published cases of MCAH, CD68 positivity on multinucleate cells in MCAH lesions suggested a fibrohistiocytic origin.² However, a number of these cases exhibited CD34 positivity, thus a macrophage origin may not be excluded.

Differential Diagnosis
The differential diagnosis for MCAH includes Kaposi sarcoma clinically and dermatofibroma and fibrous papules histologically. Sass et al²¹ determined the in vitro behavior of cultured MCAH cells to contrast markedly with Kaposi sarcoma–derived cells. Although Kaposi sarcoma–derived cells exhibited invasive behavior, cells isolated from MCAH lesions were less elongated and were unable to traverse basement membranes.

Treatment
Surgical excision or cryotherapy appear to be definitive treatments of MCAH; however, a number of cases have reported light and laser modalities as successful alternatives to excision. One case of MCAH affecting the face was treated with pulsed dye laser monotherapy.²² This modality allowed selective coagulation of the vascular structures in MCAH. At 8-month follow-up, the initial lesion was noted to be completely cleared, though similar lesions had recently appeared elsewhere on the face.²² Another case of MCAH affecting the leg was treated with pulsed dye laser and both topical and intralesional corticosteroid combination therapy. In this case, the lesion failed to respond to treatment, which may suggest that facial localization could influence response in pulsed dye laser treatment.³

Intense pulsed light also has been reported as a definitive treatment in 2 cases.^2,13 Slight erythema and transient pruritus have been reported immediately following treatment. In this case, complete resolution with only residual hyperpigmentation was reported at 2-month follow-up, with no recurrence during 12 months of follow-up.¹³

Argon laser therapy has been used in 2 cases. After a single session, lesions were no longer palpable, with no scarring noted at 8 weeks follow-up.²³ Lastly, 2 cases of MCAH have been successfully treated with the CO₂ laser, with no relapse noted at 2.5- or 5-month follow-up, respectively.²⁴

Conclusion

Multinucleate cell angiohistiocytoma is a rare and likely underdiagnosed dermatologic condition that is believed to be a reactive process. Characteristic histology of MCAH demonstrates microvascular proliferations of the dermis with multinucleate giant cells amidst a fibrous background. Although surgical excision is curative, there are reports in which laser and light therapies were used to effectively treat MCAH.

Multinucleate cell angiohistiocytoma (MCAH) is a rare benign, soft-tissue tumor first described in 1985 by Smith and Jones¹ that presents clinically as erythematous to violaceous papules most commonly affecting females on the dorsal aspect of the hands and face.² Multinucleate cell angiohistiocytoma is histologically characterized by vascular and histiocytic proliferations with dermal fibrosis. Few cases have been reported of lesions affecting the lower extremities. We report a case of MCAH affecting the legs.

Case Report

An 83-year-old white man with a history of basal cell carcinoma presented for evaluation of grouped, well-circumscribed, soft, red-violet, painless papules on the right anterior thigh that had been present for 8 months (Figure 1A). A review of symptoms was negative for immunologic, respiratory, and hematologic changes. The patient’s medical history also was remarkable for prostate cancer treated with radiation 18 years prior as well as right hip and left knee implants. The initial clinical impression was Kaposi sarcoma or a granulomatous disorder.

Histopathologic evaluation of a deep shave biopsy initially determined the lesion to be scar tissue without other pathologic findings. The patient returned to the clinic 12 months later for a complete skin examination given his history of skin cancer. Compared to clinical photographs taken a year prior, new violaceous papules were noted on the right thigh (Figure 1B) and left calf. Furthermore, there was no recurrence of the lesion at the prior biopsy site. Shave biopsies of the papules on the right thigh and left calf demonstrated similar histologic findings to each other. There was a mild increase in the number of small blood vessels in the superficial dermis (Figure 2A). A mild perivascular lymphocytic infiltrate surrounded some of these blood vessels. The endothelial cells had small nuclei with no evidence of nuclear pleomorphism. Careful examination of the interstitial dermis revealed scattered multinucleate cells with angulated cytoplasm (Figure 2B). Immunostaining for CD31 and human herpesvirus 8 were negative, excluding an infiltrative vascular tumor and Kaposi sarcoma, respectively. The diagnosis of MCAH was made based on the histopathologic findings.

At 1-year follow-up, the condition was stable with no gross changes in the lesions based on prior photographs. Once again, there was no recurrence of the excised lesions at both biopsy sites.

Comment

Presentation
A systematic review of published reports determined that 79% of MCAH cases occur in females, with an average age of onset of 50.1 years.² However, MCAH likely is underreported due to the overall lack of knowledge regarding this condition by physicians and pathologists. The hands and face are the most commonly affected areas, though other sites of involvement have been reported, including the lower extremities,^3,4 oral mucosa and upper lip,^5,6 and trunk,^7,8 as well as generalized distribution.^9-12 Additionally, 1 case presented as a single plaque on the trunk rather than having papular or nodular morphology.⁸ Multinucleate cell angiohistiocytoma lesions generally are asymptomatic, though pruritus may be present.¹³ The condition is regarded as benign, though a minority of cases have exhibited spontaneous resolution.^14-16

Histopathology
Multinucleate cell angiohistiocytoma histology demonstrates full-thickness dermal microvessel proliferation and fibrosis with characteristic multinucleate giant cells.^2,3 Vascular endothelial cells stained positive for CD68 in 60% of cases² as well as the normal endothelial markers (ie, factor VIII, CD31, CD34). The multinucleate giant cells exhibit immunoreactivity for macrophage/histiocytic markers factor XIIIa and CD68.

Etiology
The pathogenesis of MCAH is not yet fully understood, but it is considered to be a benign vascular or fibrohistiocytic neoplasm.¹⁷ Calderaro et al¹⁸ described a series of 8 patients who developed MCAH either within a cutaneous neoplastic process or in conjunction with various cutaneous reactive conditions, including hidradenitis suppurativa and chronic radiation dermatitis, as well as overlying a bone prosthesis placed due to degenerative arthritis. These cases suggest that MCAH, or possibly a subset of the disease, is a reactive process. Suggested inciting events include cancer with stromal inflammatory reaction, chronic inflammation (as seen in hidradenitis suppurativa), chronic radiation dermatitis, scarring, and vascular injury.¹⁸ Retrospective immunohistochemical evaluation of a series of MCAH cases demonstrated intralesional spindle cells to strongly express estrogen receptor alpha and factor XIIIa. Additionally, these cells sparsely expressed progesterone receptor and demonstrated no vascular endothelial growth factor immunoreactivity.¹⁹ This immunohistochemical profile supports MCAH as a distinct entity from dermatofibromas. These findings also suggest a role of hormone signaling, namely estrogen receptor alpha, in MCAH tumor biology and may offer an explanation for the predilection of MCAH in females. Furthermore, estrogen receptor positivity offers a possible mechanism for the highly vascular nature of the lesions, considering the angiogenic properties of estrogen signaling.²⁰ In a systematic review of 142 published cases of MCAH, CD68 positivity on multinucleate cells in MCAH lesions suggested a fibrohistiocytic origin.² However, a number of these cases exhibited CD34 positivity, thus a macrophage origin may not be excluded.

Differential Diagnosis
The differential diagnosis for MCAH includes Kaposi sarcoma clinically and dermatofibroma and fibrous papules histologically. Sass et al²¹ determined the in vitro behavior of cultured MCAH cells to contrast markedly with Kaposi sarcoma–derived cells. Although Kaposi sarcoma–derived cells exhibited invasive behavior, cells isolated from MCAH lesions were less elongated and were unable to traverse basement membranes.

Treatment
Surgical excision or cryotherapy appear to be definitive treatments of MCAH; however, a number of cases have reported light and laser modalities as successful alternatives to excision. One case of MCAH affecting the face was treated with pulsed dye laser monotherapy.²² This modality allowed selective coagulation of the vascular structures in MCAH. At 8-month follow-up, the initial lesion was noted to be completely cleared, though similar lesions had recently appeared elsewhere on the face.²² Another case of MCAH affecting the leg was treated with pulsed dye laser and both topical and intralesional corticosteroid combination therapy. In this case, the lesion failed to respond to treatment, which may suggest that facial localization could influence response in pulsed dye laser treatment.³

Intense pulsed light also has been reported as a definitive treatment in 2 cases.^2,13 Slight erythema and transient pruritus have been reported immediately following treatment. In this case, complete resolution with only residual hyperpigmentation was reported at 2-month follow-up, with no recurrence during 12 months of follow-up.¹³

Argon laser therapy has been used in 2 cases. After a single session, lesions were no longer palpable, with no scarring noted at 8 weeks follow-up.²³ Lastly, 2 cases of MCAH have been successfully treated with the CO₂ laser, with no relapse noted at 2.5- or 5-month follow-up, respectively.²⁴

Conclusion

Multinucleate cell angiohistiocytoma is a rare and likely underdiagnosed dermatologic condition that is believed to be a reactive process. Characteristic histology of MCAH demonstrates microvascular proliferations of the dermis with multinucleate giant cells amidst a fibrous background. Although surgical excision is curative, there are reports in which laser and light therapies were used to effectively treat MCAH.

If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.

Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.

Consider this measure:


 

Measure #109: Osteoarthritis Function and Pain Assessment

This measure is aimed at capturing the percentage of visits that included an assessment of function and pain for patients with a diagnosis of osteoarthritis (OA) who are aged 21 years or older.

What you need to do: Perform an assessment of symptoms and functional status for patients with OA and document it in the medical record. Validated scales and questionnaires may be used but are not required.

Eligible cases include patients aged 21 years and older with a diagnosis of OA and a patient encounter during the performance period. Applicable codes include (CPT): 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215.

To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, CPT II 1006F indicates that OA symptoms and functional status were assessed. Add the 8P modifier to CPT II 1006F if the assessment was not performed and the reason is not otherwise specified.

CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.

Certain clinicians are exempt from reporting and do not face a penalty under MIPS:

• Those who enrolled in Medicare for the first time during a performance period.
• Those who have Medicare Part B allowed charges of $30,000 or less.
• Those who have 100 or fewer Medicare Part B patients.
• Those who are significantly participating in an Advanced Alternative Payment Model (APM).

If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.

Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.

Consider this measure:


 

Measure #109: Osteoarthritis Function and Pain Assessment

This measure is aimed at capturing the percentage of visits that included an assessment of function and pain for patients with a diagnosis of osteoarthritis (OA) who are aged 21 years or older.

What you need to do: Perform an assessment of symptoms and functional status for patients with OA and document it in the medical record. Validated scales and questionnaires may be used but are not required.

Eligible cases include patients aged 21 years and older with a diagnosis of OA and a patient encounter during the performance period. Applicable codes include (CPT): 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215.

To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, CPT II 1006F indicates that OA symptoms and functional status were assessed. Add the 8P modifier to CPT II 1006F if the assessment was not performed and the reason is not otherwise specified.

CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.

Certain clinicians are exempt from reporting and do not face a penalty under MIPS:

• Those who enrolled in Medicare for the first time during a performance period.
• Those who have Medicare Part B allowed charges of $30,000 or less.
• Those who have 100 or fewer Medicare Part B patients.
• Those who are significantly participating in an Advanced Alternative Payment Model (APM).

If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.

Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.

Consider this measure:


 

Measure #109: Osteoarthritis Function and Pain Assessment

This measure is aimed at capturing the percentage of visits that included an assessment of function and pain for patients with a diagnosis of osteoarthritis (OA) who are aged 21 years or older.

What you need to do: Perform an assessment of symptoms and functional status for patients with OA and document it in the medical record. Validated scales and questionnaires may be used but are not required.

Eligible cases include patients aged 21 years and older with a diagnosis of OA and a patient encounter during the performance period. Applicable codes include (CPT): 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215.

To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, CPT II 1006F indicates that OA symptoms and functional status were assessed. Add the 8P modifier to CPT II 1006F if the assessment was not performed and the reason is not otherwise specified.

CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.

Certain clinicians are exempt from reporting and do not face a penalty under MIPS:

• Those who enrolled in Medicare for the first time during a performance period.
• Those who have Medicare Part B allowed charges of $30,000 or less.
• Those who have 100 or fewer Medicare Part B patients.
• Those who are significantly participating in an Advanced Alternative Payment Model (APM).