Article

Since the end of 2019, COVID-19 infection caused by SARS-CoV-2 has spread in a worldwide pandemic. The first cutaneous manifestations possibly linked to COVID-19 were reported in spring 2020.¹ Herpes zoster (HZ) was suspected as a predictive cutaneous manifestation of COVID-19 with a debated prognostic significance.² The end of 2020 was marked with the beginning of vaccination against COVID-19, and safety studies reported few side effects after vaccination with nucleoside-modified messenger RNA (mRNA) COVID-19 vaccines.³ Real-life use of vaccines could lead to the occurrence of potential side effects (or fortuitous medical events) that were not observed in these studies. We report a series of 5 cases of HZ occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine extracted from a declarative cohort of cutaneous reactions in our vaccination center.

Case Series

We identified 2 men and 3 women (Table) who experienced HZ after vaccination with a nucleoside-modified mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech). Patients fulfilled French governmental criteria for vaccination at the time of the report—older than 75 years or a health care professional—and they were vaccinated at the vaccination center of a French university hospital. The median age of the patients was 56 years (interquartile range [IQR], 51–82 years). One patient was diagnosed with COVID-19 in February 2020. A medical history of HZ was found in 1 patient. No medical history of immunosuppression was noted. Herpes zoster was observed on the same side of the body as the vaccination site in 4 patients. The median delay before the onset of symptoms was 6 days (IQR, 1–15 days) after injection. The median duration of the symptoms was 13 days (IQR, 11.5–16.5 days). Clinical signs of HZ were mild with few vesicles in 4 patients, and we observed a notably long delay between the onset of pain and the eruption of vesicles in 2 cases (4 and 10 days, respectively). The clinical diagnosis of HZ was confirmed by a dermatologist for all patients (Figures 1 and 2). Polymerase chain reaction assays for the detection of the varicella-zoster virus were performed in 2 cases and were positive. A complete blood cell count was performed in 1 patient, and we observed isolated lymphopenia (500/mm³ [reference range, 1000–4000/mm³]). Herpes zoster occurred after the first dose of vaccine in 4 patients and after the second dose for 1 patient. Three patients were treated with antiviral therapy (acyclovir) for 7 days. Three patients recovered from symptoms within 2 weeks and 2 patients within 1 week.

Comment

We report a series of HZ cases occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine. We did not observe complicated HZ, and most of the time, HZ lesions were located on the same side of the body as the vaccine injection. One case of HZ after COVID-19 vaccination was reported by Bostan and Yalici-Armagan,⁴ but it followed injection with an inactivated vaccine, which is different from our series. Herpes zoster remains rarely reported, mainly following mRNA COVID-19 vaccination.⁵

Cases of HZ after vaccination have been reported after the live attenuated zoster or yellow fever vaccines, but HZ should not appear as a concomitant effect after any type of vaccines.^6,7 Kawai et al⁸ reported that the incidence rate of HZ ranged from 3 to 5 cases per 1000 person-years in North America, Europe, and Asia-Pacific. The risk for recurrence of HZ ranged from 1% to 6% depending on the type of study design, age distribution of studied populations, and definition.⁸ In another retrospective database analysis in Israel, the incidence density rate of HZ was 3.46 cases per 1000 person-years in the total population and 12.8 cases per 1000 person-years in immunocompromised patients, therefore the immunocompromised status is important to consider.⁹

In our declarative cohort of skin eruptions before vaccination, we recorded 11 cases of HZ among 148 skin eruptions (7.43%) at the time of the study, but the design of the study did not allow us to estimate the exact incidence of HZ in the global COVID-19–vaccinated population because our study was not based on a systematic and prospective analysis of all vaccinated patients. The comparison between the prevalence of HZ in the COVID-19–vaccinated population and the nonvaccinated population is difficult owing to the lack of data about HZ in the nonvaccinated population at the time of our analysis. Furthermore, we did not include all vaccinated patients in a prospective follow-up. We highlight the importance of medical history of patients that differed between vaccinated patients (at the time of our analysis) and the global population due to French governmental access criteria to vaccination. The link to prior SARS-CoV-2 infection was uncertain because a medical history of COVID-19 was found in only 1 patient. Only 1 patient had a history of HZ, which is not a contraindication of COVID-19 vaccination.

Postinjection pains are frequent with COVID-19 vaccines, but clinical signs such as extension of pain, burning sensation, and eruption of vesicles should lead the physician to consider the diagnosis of HZ, regardless of the delay between the injection and the symptoms. Indeed, the onset of symptoms could be late, and the clinical presentation initially may be mistaken for an injection-site reaction, which is a frequent known side effect of vaccines. These new cases do not prove causality between COVID-19 vaccination and HZ. Varicella-zoster virus remains latent in dorsal-root or ganglia after primary infection, and HZ caused by reactivation of varicella-zoster virus may occur spontaneously or be triggered. In our series, we did not observe medical history of immunosuppression, and no other known risk factors of HZ (eg, radiation therapy, physical trauma, fever after vaccination) were recorded. The pathophysiologic mechanism remains elusive, but local vaccine-induced immunomodulation or an inflammatory state may be involved.

Conclusion

Our case series highlights that clinicians must remain vigilant to diagnose HZ early to prevent potential complications, such as postherpetic neuralgia. Also, vaccination should not be contraindicated in patients with medical history of HZ; the occurrence of HZ does not justify avoiding the second injection of the vaccine due to the benefit of vaccination.

Since the end of 2019, COVID-19 infection caused by SARS-CoV-2 has spread in a worldwide pandemic. The first cutaneous manifestations possibly linked to COVID-19 were reported in spring 2020.¹ Herpes zoster (HZ) was suspected as a predictive cutaneous manifestation of COVID-19 with a debated prognostic significance.² The end of 2020 was marked with the beginning of vaccination against COVID-19, and safety studies reported few side effects after vaccination with nucleoside-modified messenger RNA (mRNA) COVID-19 vaccines.³ Real-life use of vaccines could lead to the occurrence of potential side effects (or fortuitous medical events) that were not observed in these studies. We report a series of 5 cases of HZ occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine extracted from a declarative cohort of cutaneous reactions in our vaccination center.

Case Series

We identified 2 men and 3 women (Table) who experienced HZ after vaccination with a nucleoside-modified mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech). Patients fulfilled French governmental criteria for vaccination at the time of the report—older than 75 years or a health care professional—and they were vaccinated at the vaccination center of a French university hospital. The median age of the patients was 56 years (interquartile range [IQR], 51–82 years). One patient was diagnosed with COVID-19 in February 2020. A medical history of HZ was found in 1 patient. No medical history of immunosuppression was noted. Herpes zoster was observed on the same side of the body as the vaccination site in 4 patients. The median delay before the onset of symptoms was 6 days (IQR, 1–15 days) after injection. The median duration of the symptoms was 13 days (IQR, 11.5–16.5 days). Clinical signs of HZ were mild with few vesicles in 4 patients, and we observed a notably long delay between the onset of pain and the eruption of vesicles in 2 cases (4 and 10 days, respectively). The clinical diagnosis of HZ was confirmed by a dermatologist for all patients (Figures 1 and 2). Polymerase chain reaction assays for the detection of the varicella-zoster virus were performed in 2 cases and were positive. A complete blood cell count was performed in 1 patient, and we observed isolated lymphopenia (500/mm³ [reference range, 1000–4000/mm³]). Herpes zoster occurred after the first dose of vaccine in 4 patients and after the second dose for 1 patient. Three patients were treated with antiviral therapy (acyclovir) for 7 days. Three patients recovered from symptoms within 2 weeks and 2 patients within 1 week.

Comment

We report a series of HZ cases occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine. We did not observe complicated HZ, and most of the time, HZ lesions were located on the same side of the body as the vaccine injection. One case of HZ after COVID-19 vaccination was reported by Bostan and Yalici-Armagan,⁴ but it followed injection with an inactivated vaccine, which is different from our series. Herpes zoster remains rarely reported, mainly following mRNA COVID-19 vaccination.⁵

Cases of HZ after vaccination have been reported after the live attenuated zoster or yellow fever vaccines, but HZ should not appear as a concomitant effect after any type of vaccines.^6,7 Kawai et al⁸ reported that the incidence rate of HZ ranged from 3 to 5 cases per 1000 person-years in North America, Europe, and Asia-Pacific. The risk for recurrence of HZ ranged from 1% to 6% depending on the type of study design, age distribution of studied populations, and definition.⁸ In another retrospective database analysis in Israel, the incidence density rate of HZ was 3.46 cases per 1000 person-years in the total population and 12.8 cases per 1000 person-years in immunocompromised patients, therefore the immunocompromised status is important to consider.⁹

In our declarative cohort of skin eruptions before vaccination, we recorded 11 cases of HZ among 148 skin eruptions (7.43%) at the time of the study, but the design of the study did not allow us to estimate the exact incidence of HZ in the global COVID-19–vaccinated population because our study was not based on a systematic and prospective analysis of all vaccinated patients. The comparison between the prevalence of HZ in the COVID-19–vaccinated population and the nonvaccinated population is difficult owing to the lack of data about HZ in the nonvaccinated population at the time of our analysis. Furthermore, we did not include all vaccinated patients in a prospective follow-up. We highlight the importance of medical history of patients that differed between vaccinated patients (at the time of our analysis) and the global population due to French governmental access criteria to vaccination. The link to prior SARS-CoV-2 infection was uncertain because a medical history of COVID-19 was found in only 1 patient. Only 1 patient had a history of HZ, which is not a contraindication of COVID-19 vaccination.

Postinjection pains are frequent with COVID-19 vaccines, but clinical signs such as extension of pain, burning sensation, and eruption of vesicles should lead the physician to consider the diagnosis of HZ, regardless of the delay between the injection and the symptoms. Indeed, the onset of symptoms could be late, and the clinical presentation initially may be mistaken for an injection-site reaction, which is a frequent known side effect of vaccines. These new cases do not prove causality between COVID-19 vaccination and HZ. Varicella-zoster virus remains latent in dorsal-root or ganglia after primary infection, and HZ caused by reactivation of varicella-zoster virus may occur spontaneously or be triggered. In our series, we did not observe medical history of immunosuppression, and no other known risk factors of HZ (eg, radiation therapy, physical trauma, fever after vaccination) were recorded. The pathophysiologic mechanism remains elusive, but local vaccine-induced immunomodulation or an inflammatory state may be involved.

Conclusion

Our case series highlights that clinicians must remain vigilant to diagnose HZ early to prevent potential complications, such as postherpetic neuralgia. Also, vaccination should not be contraindicated in patients with medical history of HZ; the occurrence of HZ does not justify avoiding the second injection of the vaccine due to the benefit of vaccination.

Since the end of 2019, COVID-19 infection caused by SARS-CoV-2 has spread in a worldwide pandemic. The first cutaneous manifestations possibly linked to COVID-19 were reported in spring 2020.¹ Herpes zoster (HZ) was suspected as a predictive cutaneous manifestation of COVID-19 with a debated prognostic significance.² The end of 2020 was marked with the beginning of vaccination against COVID-19, and safety studies reported few side effects after vaccination with nucleoside-modified messenger RNA (mRNA) COVID-19 vaccines.³ Real-life use of vaccines could lead to the occurrence of potential side effects (or fortuitous medical events) that were not observed in these studies. We report a series of 5 cases of HZ occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine extracted from a declarative cohort of cutaneous reactions in our vaccination center.

Case Series

We identified 2 men and 3 women (Table) who experienced HZ after vaccination with a nucleoside-modified mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech). Patients fulfilled French governmental criteria for vaccination at the time of the report—older than 75 years or a health care professional—and they were vaccinated at the vaccination center of a French university hospital. The median age of the patients was 56 years (interquartile range [IQR], 51–82 years). One patient was diagnosed with COVID-19 in February 2020. A medical history of HZ was found in 1 patient. No medical history of immunosuppression was noted. Herpes zoster was observed on the same side of the body as the vaccination site in 4 patients. The median delay before the onset of symptoms was 6 days (IQR, 1–15 days) after injection. The median duration of the symptoms was 13 days (IQR, 11.5–16.5 days). Clinical signs of HZ were mild with few vesicles in 4 patients, and we observed a notably long delay between the onset of pain and the eruption of vesicles in 2 cases (4 and 10 days, respectively). The clinical diagnosis of HZ was confirmed by a dermatologist for all patients (Figures 1 and 2). Polymerase chain reaction assays for the detection of the varicella-zoster virus were performed in 2 cases and were positive. A complete blood cell count was performed in 1 patient, and we observed isolated lymphopenia (500/mm³ [reference range, 1000–4000/mm³]). Herpes zoster occurred after the first dose of vaccine in 4 patients and after the second dose for 1 patient. Three patients were treated with antiviral therapy (acyclovir) for 7 days. Three patients recovered from symptoms within 2 weeks and 2 patients within 1 week.

Comment

We report a series of HZ cases occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine. We did not observe complicated HZ, and most of the time, HZ lesions were located on the same side of the body as the vaccine injection. One case of HZ after COVID-19 vaccination was reported by Bostan and Yalici-Armagan,⁴ but it followed injection with an inactivated vaccine, which is different from our series. Herpes zoster remains rarely reported, mainly following mRNA COVID-19 vaccination.⁵

Cases of HZ after vaccination have been reported after the live attenuated zoster or yellow fever vaccines, but HZ should not appear as a concomitant effect after any type of vaccines.^6,7 Kawai et al⁸ reported that the incidence rate of HZ ranged from 3 to 5 cases per 1000 person-years in North America, Europe, and Asia-Pacific. The risk for recurrence of HZ ranged from 1% to 6% depending on the type of study design, age distribution of studied populations, and definition.⁸ In another retrospective database analysis in Israel, the incidence density rate of HZ was 3.46 cases per 1000 person-years in the total population and 12.8 cases per 1000 person-years in immunocompromised patients, therefore the immunocompromised status is important to consider.⁹

In our declarative cohort of skin eruptions before vaccination, we recorded 11 cases of HZ among 148 skin eruptions (7.43%) at the time of the study, but the design of the study did not allow us to estimate the exact incidence of HZ in the global COVID-19–vaccinated population because our study was not based on a systematic and prospective analysis of all vaccinated patients. The comparison between the prevalence of HZ in the COVID-19–vaccinated population and the nonvaccinated population is difficult owing to the lack of data about HZ in the nonvaccinated population at the time of our analysis. Furthermore, we did not include all vaccinated patients in a prospective follow-up. We highlight the importance of medical history of patients that differed between vaccinated patients (at the time of our analysis) and the global population due to French governmental access criteria to vaccination. The link to prior SARS-CoV-2 infection was uncertain because a medical history of COVID-19 was found in only 1 patient. Only 1 patient had a history of HZ, which is not a contraindication of COVID-19 vaccination.

Postinjection pains are frequent with COVID-19 vaccines, but clinical signs such as extension of pain, burning sensation, and eruption of vesicles should lead the physician to consider the diagnosis of HZ, regardless of the delay between the injection and the symptoms. Indeed, the onset of symptoms could be late, and the clinical presentation initially may be mistaken for an injection-site reaction, which is a frequent known side effect of vaccines. These new cases do not prove causality between COVID-19 vaccination and HZ. Varicella-zoster virus remains latent in dorsal-root or ganglia after primary infection, and HZ caused by reactivation of varicella-zoster virus may occur spontaneously or be triggered. In our series, we did not observe medical history of immunosuppression, and no other known risk factors of HZ (eg, radiation therapy, physical trauma, fever after vaccination) were recorded. The pathophysiologic mechanism remains elusive, but local vaccine-induced immunomodulation or an inflammatory state may be involved.

Conclusion

Our case series highlights that clinicians must remain vigilant to diagnose HZ early to prevent potential complications, such as postherpetic neuralgia. Also, vaccination should not be contraindicated in patients with medical history of HZ; the occurrence of HZ does not justify avoiding the second injection of the vaccine due to the benefit of vaccination.

To the Editor:

Securing a dermatology residency position is extraordinarily competitive. The match rate for US allopathic seniors for dermatology is 84.7%, among the lowest of all medical specialties. Matched dermatology applicants boast a mean US Medical Licensing Examination (USMLE) Step 1 score of 248, the second highest of all specialties.¹ To gain an edge, applicants are faced with decisions regarding pursuit of dedicated research time and additional professional degrees.

We conducted a cross-sectional study to determine how many dermatology residency applicants pursue additional years of training and how this decision relates to USMLE scores and other metrics. This study was approved by the University of Michigan institutional review board. Using Electronic Residency Application Service applicant data, all applicants to the University of Michigan Medical School (Ann Arbor, Michigan) dermatology residency program for the 2018-2019 application cycle were included.

Analysis of variance was performed to determine differences in mean USMLE Step 1 scores, Step 2 Clinical Knowledge scores, and number of research experiences (eg, presentations, publications) between groups. A 2-tailed z test of independent samples was performed for individual pairwise subgroup analyses.

There were 608 (377 female, 231 male; mean age, 27.9 years) applicants from 199 different medical schools; 550 graduated with an MD degree, 40 with a DO degree, and 18 were international medical graduates (IMGs)(eg, MBBS, MBBCh, BAO, MBChB). One hundred eighty-four applicants (30.2%) pursued either a second professional degree or a dedicated research period lasting at least 12 months. Twenty-eight applicants (4.6%) obtained a master’s degree, 21 (3.5%) obtained a doctorate, and 135 (22.2%) pursued dedicated research.

Of the 40 DO applicants, 1 (2.5%) pursued dedicated research time; 0 (zero) completed a dual degree. None (zero) of the 18 IMGs pursued a dual degree or dedicated research time. When the scores of applicants who pursued additional training and the scores of applicants who did not were compared, neither mean USMLE Step 1 scores nor mean USMLE Step 2 Clinical Knowledge scores were statistically different (P=.31 and P=.44, respectively). Applicants who completed medical school in 4 years had fewer research experiences (mean [SD] experiences, 13.9 [13.2]) than students with a master’s degree (18.5 [8.4]), doctorate (24.5 [17.5]), or dedicated research time (23.9 [14.9])(P<.001).

Utilizing US News & World Report rankings (2019 Best Medical Schools: Research), we determined that 146 applicants (24.0%) attended a top 25 medical school in 2019.² Of those 146 applicants, 77 (52.7%) pursued additional training through dedicated research or a second professional degree. Only 107 of the 462 applicants (23.2%) from medical schools that were not in the top 25 as determined by the US News & World Report pursued additional training (P<.0001)(Figure).

There is sentiment among applicants that a weaker dermatology residency application can be bolstered through a dedicated research year or a second professional degree. Whether this additional training has an impact on an applicant’s chances of matching is unclear and requires further investigation. Our data showed that applicants from the top 25 medical schools were more likely to pursue additional training than graduates at other institutions. These highly ranked academic institutions might encourage students to pursue a dual degree or research fellowship. In addition, year-long research opportunities might be more available through top medical schools; these schools might be more likely to offer dual-degree programs or provide funding to support student research opportunities.

It is important to comment on the potential importance of funding to support research years; the unpaid nature of many research fellowships in dermatology tends to favor applicants from a higher socioeconomic background. In that respect, the pervasive trend of encouraging research years in dermatology might widen already apparent disparities in our field, likely impacting underrepresented minorities disproportionately.³ Importantly, students with an MD degree represent nearly all applicants who completed a dual degree or dedicated research time. This might be due to fewer opportunities available to IMGs and DO students or secondary to incentivization by MD institutions.

Our data also suggest that students who pursue additional training have academic achievement metrics similar to those who do not. Additional training might increase medical students’ debt burden, thus catering to more affluent applicants, which, in turn, might have an impact on the diversity of the dermatology residency applicant pool.

Our data come from a single institution during a single application cycle, comprising 608 applicants. Nationwide, there were 701 dermatology residency applicants for the 2018-2019 application cycle; our pool therefore represents most (86.7%) but not all applicants.

We decided to use the US News & World Report 2019 rankings to identify top medical schools. Although this ranking system is imperfect and inherently subjective, it is widely utilized by prospective applicants and administrative faculty; we deemed it the best ranking that we could utilize to identify top medical schools. Because the University of Michigan Medical School was in the top 25 of Best Medical Schools: Research, according to the US News & World Report 2019 rankings, our applicant pool might be skewed to applicants interested in a more academic, research-focused residency program.

Our study revealed that 30% (n=184) of dermatology residency applicants pursued a second professional degree or dedicated research time. There was no difference in UMLE Step 1 and Step 2 scores for those who pursued additional training compared to those who did not.

To the Editor:

Securing a dermatology residency position is extraordinarily competitive. The match rate for US allopathic seniors for dermatology is 84.7%, among the lowest of all medical specialties. Matched dermatology applicants boast a mean US Medical Licensing Examination (USMLE) Step 1 score of 248, the second highest of all specialties.¹ To gain an edge, applicants are faced with decisions regarding pursuit of dedicated research time and additional professional degrees.

We conducted a cross-sectional study to determine how many dermatology residency applicants pursue additional years of training and how this decision relates to USMLE scores and other metrics. This study was approved by the University of Michigan institutional review board. Using Electronic Residency Application Service applicant data, all applicants to the University of Michigan Medical School (Ann Arbor, Michigan) dermatology residency program for the 2018-2019 application cycle were included.

Analysis of variance was performed to determine differences in mean USMLE Step 1 scores, Step 2 Clinical Knowledge scores, and number of research experiences (eg, presentations, publications) between groups. A 2-tailed z test of independent samples was performed for individual pairwise subgroup analyses.

There were 608 (377 female, 231 male; mean age, 27.9 years) applicants from 199 different medical schools; 550 graduated with an MD degree, 40 with a DO degree, and 18 were international medical graduates (IMGs)(eg, MBBS, MBBCh, BAO, MBChB). One hundred eighty-four applicants (30.2%) pursued either a second professional degree or a dedicated research period lasting at least 12 months. Twenty-eight applicants (4.6%) obtained a master’s degree, 21 (3.5%) obtained a doctorate, and 135 (22.2%) pursued dedicated research.

Of the 40 DO applicants, 1 (2.5%) pursued dedicated research time; 0 (zero) completed a dual degree. None (zero) of the 18 IMGs pursued a dual degree or dedicated research time. When the scores of applicants who pursued additional training and the scores of applicants who did not were compared, neither mean USMLE Step 1 scores nor mean USMLE Step 2 Clinical Knowledge scores were statistically different (P=.31 and P=.44, respectively). Applicants who completed medical school in 4 years had fewer research experiences (mean [SD] experiences, 13.9 [13.2]) than students with a master’s degree (18.5 [8.4]), doctorate (24.5 [17.5]), or dedicated research time (23.9 [14.9])(P<.001).

Utilizing US News & World Report rankings (2019 Best Medical Schools: Research), we determined that 146 applicants (24.0%) attended a top 25 medical school in 2019.² Of those 146 applicants, 77 (52.7%) pursued additional training through dedicated research or a second professional degree. Only 107 of the 462 applicants (23.2%) from medical schools that were not in the top 25 as determined by the US News & World Report pursued additional training (P<.0001)(Figure).

There is sentiment among applicants that a weaker dermatology residency application can be bolstered through a dedicated research year or a second professional degree. Whether this additional training has an impact on an applicant’s chances of matching is unclear and requires further investigation. Our data showed that applicants from the top 25 medical schools were more likely to pursue additional training than graduates at other institutions. These highly ranked academic institutions might encourage students to pursue a dual degree or research fellowship. In addition, year-long research opportunities might be more available through top medical schools; these schools might be more likely to offer dual-degree programs or provide funding to support student research opportunities.

It is important to comment on the potential importance of funding to support research years; the unpaid nature of many research fellowships in dermatology tends to favor applicants from a higher socioeconomic background. In that respect, the pervasive trend of encouraging research years in dermatology might widen already apparent disparities in our field, likely impacting underrepresented minorities disproportionately.³ Importantly, students with an MD degree represent nearly all applicants who completed a dual degree or dedicated research time. This might be due to fewer opportunities available to IMGs and DO students or secondary to incentivization by MD institutions.

Our data also suggest that students who pursue additional training have academic achievement metrics similar to those who do not. Additional training might increase medical students’ debt burden, thus catering to more affluent applicants, which, in turn, might have an impact on the diversity of the dermatology residency applicant pool.

Our data come from a single institution during a single application cycle, comprising 608 applicants. Nationwide, there were 701 dermatology residency applicants for the 2018-2019 application cycle; our pool therefore represents most (86.7%) but not all applicants.

We decided to use the US News & World Report 2019 rankings to identify top medical schools. Although this ranking system is imperfect and inherently subjective, it is widely utilized by prospective applicants and administrative faculty; we deemed it the best ranking that we could utilize to identify top medical schools. Because the University of Michigan Medical School was in the top 25 of Best Medical Schools: Research, according to the US News & World Report 2019 rankings, our applicant pool might be skewed to applicants interested in a more academic, research-focused residency program.

Our study revealed that 30% (n=184) of dermatology residency applicants pursued a second professional degree or dedicated research time. There was no difference in UMLE Step 1 and Step 2 scores for those who pursued additional training compared to those who did not.

To the Editor:

Securing a dermatology residency position is extraordinarily competitive. The match rate for US allopathic seniors for dermatology is 84.7%, among the lowest of all medical specialties. Matched dermatology applicants boast a mean US Medical Licensing Examination (USMLE) Step 1 score of 248, the second highest of all specialties.¹ To gain an edge, applicants are faced with decisions regarding pursuit of dedicated research time and additional professional degrees.

We conducted a cross-sectional study to determine how many dermatology residency applicants pursue additional years of training and how this decision relates to USMLE scores and other metrics. This study was approved by the University of Michigan institutional review board. Using Electronic Residency Application Service applicant data, all applicants to the University of Michigan Medical School (Ann Arbor, Michigan) dermatology residency program for the 2018-2019 application cycle were included.

Analysis of variance was performed to determine differences in mean USMLE Step 1 scores, Step 2 Clinical Knowledge scores, and number of research experiences (eg, presentations, publications) between groups. A 2-tailed z test of independent samples was performed for individual pairwise subgroup analyses.

There were 608 (377 female, 231 male; mean age, 27.9 years) applicants from 199 different medical schools; 550 graduated with an MD degree, 40 with a DO degree, and 18 were international medical graduates (IMGs)(eg, MBBS, MBBCh, BAO, MBChB). One hundred eighty-four applicants (30.2%) pursued either a second professional degree or a dedicated research period lasting at least 12 months. Twenty-eight applicants (4.6%) obtained a master’s degree, 21 (3.5%) obtained a doctorate, and 135 (22.2%) pursued dedicated research.

Of the 40 DO applicants, 1 (2.5%) pursued dedicated research time; 0 (zero) completed a dual degree. None (zero) of the 18 IMGs pursued a dual degree or dedicated research time. When the scores of applicants who pursued additional training and the scores of applicants who did not were compared, neither mean USMLE Step 1 scores nor mean USMLE Step 2 Clinical Knowledge scores were statistically different (P=.31 and P=.44, respectively). Applicants who completed medical school in 4 years had fewer research experiences (mean [SD] experiences, 13.9 [13.2]) than students with a master’s degree (18.5 [8.4]), doctorate (24.5 [17.5]), or dedicated research time (23.9 [14.9])(P<.001).

Utilizing US News & World Report rankings (2019 Best Medical Schools: Research), we determined that 146 applicants (24.0%) attended a top 25 medical school in 2019.² Of those 146 applicants, 77 (52.7%) pursued additional training through dedicated research or a second professional degree. Only 107 of the 462 applicants (23.2%) from medical schools that were not in the top 25 as determined by the US News & World Report pursued additional training (P<.0001)(Figure).

There is sentiment among applicants that a weaker dermatology residency application can be bolstered through a dedicated research year or a second professional degree. Whether this additional training has an impact on an applicant’s chances of matching is unclear and requires further investigation. Our data showed that applicants from the top 25 medical schools were more likely to pursue additional training than graduates at other institutions. These highly ranked academic institutions might encourage students to pursue a dual degree or research fellowship. In addition, year-long research opportunities might be more available through top medical schools; these schools might be more likely to offer dual-degree programs or provide funding to support student research opportunities.

It is important to comment on the potential importance of funding to support research years; the unpaid nature of many research fellowships in dermatology tends to favor applicants from a higher socioeconomic background. In that respect, the pervasive trend of encouraging research years in dermatology might widen already apparent disparities in our field, likely impacting underrepresented minorities disproportionately.³ Importantly, students with an MD degree represent nearly all applicants who completed a dual degree or dedicated research time. This might be due to fewer opportunities available to IMGs and DO students or secondary to incentivization by MD institutions.

Our data also suggest that students who pursue additional training have academic achievement metrics similar to those who do not. Additional training might increase medical students’ debt burden, thus catering to more affluent applicants, which, in turn, might have an impact on the diversity of the dermatology residency applicant pool.

Our data come from a single institution during a single application cycle, comprising 608 applicants. Nationwide, there were 701 dermatology residency applicants for the 2018-2019 application cycle; our pool therefore represents most (86.7%) but not all applicants.

We decided to use the US News & World Report 2019 rankings to identify top medical schools. Although this ranking system is imperfect and inherently subjective, it is widely utilized by prospective applicants and administrative faculty; we deemed it the best ranking that we could utilize to identify top medical schools. Because the University of Michigan Medical School was in the top 25 of Best Medical Schools: Research, according to the US News & World Report 2019 rankings, our applicant pool might be skewed to applicants interested in a more academic, research-focused residency program.

Our study revealed that 30% (n=184) of dermatology residency applicants pursued a second professional degree or dedicated research time. There was no difference in UMLE Step 1 and Step 2 scores for those who pursued additional training compared to those who did not.

To the Editor:

Pityriasis lichenoides is a papulosquamous dermatologic disorder that is characterized by recurrent papules.¹ There is a spectrum of disease in pityriasis lichenoides that includes pityriasis lichenoides et varioliformis acuta (PLEVA) at one end and pityriasis lichenoides chronica at the other. Pityriasis lichenoides et varioliformis acuta is more common in younger individuals and is characterized by erythematous papules that often crust; these lesions resolve over weeks. The lesions of pityriasis lichenoides chronica are characteristically scaly, pink to red-brown papules that tend to resolve over months.¹

Histologically, PLEVA exhibits parakeratosis, interface dermatitis, and a wedge-shaped infiltrate.¹ Necrotic keratinocytes and extravasated erythrocytes also are common features. Additionally, monoclonal T cells may be present in the infiltrate.¹

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare and severe variant of PLEVA. Febrile ulceronecrotic Mucha-Habermann disease is characterized by ulceronecrotic lesions, fever, and systemic symptoms.² Herein, we present a case of FUMHD.

A 57-year-old man presented with an eruption of painful lesions involving the face, trunk, arms, legs, and genitalia of 1 month’s duration. The patient denied oral and ocular involvement. He had soreness and swelling of the arms and legs. A prior 12-day course of prednisone prescribed by a community dermatologist failed to improve the rash. A biopsy performed by a community dermatologist was nondiagnostic. The patient denied fever but did report chills. He had no preceding illness and was not taking new medications. On physical examination, the patient was afebrile and normotensive with innumerable deep-seated pustules and crusted ulcerations on the face, palms, soles, trunk, extremities, and penis (Figures 1 and 2). There was a background morbilliform eruption on the trunk. The ocular and oral mucosae were spared. The upper and lower extremities had pitting edema.

The patient’s alanine aminotransaminase and aspartate aminotransaminase levels were elevated at 55 and 51 U/L, respectively. His white blood cell count was within reference range; however, there was an elevated absolute neutrophil count (8.7×10³/μL). No eosinophilia was noted. Laboratory evaluation showed a positive antimitochondrial antibody, and magnetic resonance imaging showed evidence of steatohepatitis. Punch biopsies from both the morbilliform eruption and a deep-seated pustule showed epidermal necrosis, parakeratosis, necrotic keratinocytes, and a lichenoid infiltrate of lymphocytes at the dermoepidermal interface. In the dermis, there was a wedge-shaped superficial and deep, perivascular infiltrate with extravasated erythrocytes (Figures 3 and 4). Tissue Gram stain was negative for bacteria. Varicella-zoster virus and herpes simplex virus immunostains were negative. Direct immunofluorescence showed colloid bodies, as can be seen in lichenoid dermatitis.

At the next clinic visit, the patient reported a fever of 39.4 °C. After reviewing the patient’s histopathology and clinical picture, along with the presence of fever, a final diagnosis of FUMHD was made. The patient was started on an oral regimen of prednisone 80 mg once daily, minocycline 100 mg twice daily, and methotrexate 15 mg weekly. Unna boots (specialized compression wraps) with triamcinolone acetonide ointment 0.1% were placed weekly until the leg edema and ulcerations healed. He was maintained on methotrexate 15 mg weekly and 5 to 10 mg of prednisone once daily. The patient demonstrated residual scarring, with only rare new papulonodules that did not ulcerate when attempts were made to taper his medications. He was followed for nearly 3 years, with a recurrence of symptoms 2 years and 3 months after initial presentation to the academic dermatology clinic.

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of PLEVA that can present with the rapid appearance of necrotic skin lesions, fever, and systemic manifestations, including pulmonary, gastrointestinal, central nervous system, cardiac, hematologic, and rheumatologic symptoms.^2-4 The evolution from PLEVA to FUMHD ranges from days to weeks, and patientsrarely can have an initial presentation of FUMHD.² The duration of illness has been reported to be 1 to 24 months⁵; however, the length of illness still remains unclear, as many studies of FUMHD are case reports with limited follow-up. Our patient had a disease duration of at least 27 months. The lesions of FUMHD usually are generalized with flexural prominence, and mucosal involvement occurs in approximately one-quarter of cases. Hypertrophic scarring may be seen after the ulcerated lesions heal.² The incidence of FUMHD is higher in men than in women, and it is more common in younger individuals.^2,6 There have been reported fatalities associated with FUMHD, mostly in adults.^2,4

The clinical differential diagnosis for PLEVA includes disseminated herpes zoster, varicella-zoster virus or coxsackievirus infections, lymphomatoid papulosis, angiodestructive lymphoma such as extranodal natural killer/T-cell lymphoma, drug eruption, arthropod bite, erythema multiforme, ecthyma, ecthyma gangrenosum, necrotic folliculitis, and cutaneous small vessel vasculitis. To differentiate between these diagnoses and PLEVA or FUMHD, it is important to take a strong clinical history. For example, for varicella-zoster virus and coxsackievirus infections, exposure history to the viruses and vaccination history for varicella-zoster virus can help elucidate the diagnosis.

Skin biopsy can help differentiate between these entities and PLEVA or FUMHD. The histopathology of a nonulcerated lesion of FUMHD shows parakeratosis, spongiosis, and lymphocyte exocytosis, as well as lymphocytic vasculitis—findings commonly seen in PLEVA. With the ulceronecrotic lesions of FUMHD, epidermal necrosis and ulceration can be seen microscopically.² Although skin biopsy is not absolutely necessary for making the diagnosis of PLEVA, it can be helpful.³ However, given the dramatic and extreme clinical impression with an extensive differential diagnosis that includes disorders ranging from infectious to neoplastic, biopsy of FUMHD with clinicopathologic correlation often is required.

It is important to avoid biopsying ulcerated lesions of FUMHD, as the histopathologic findings are more likely to be nonspecific. Additionally, nonspecific features often are seen with immunohistochemistry; abnormal laboratory testing may be seen in FUMHD, but there is no specific test to diagnose FUMHD.² Finally, a predominantly CD8⁺ cell infiltrate was seen in 4 of 6 cases of FUMHD, with 2 cases showing a mixed infiltrate of CD8⁺ and CD4⁺ cells.^5,7-10

Although no unified diagnostic criterion exists for FUMHD, Nofal et al² proposed criteria comprised of constant features, which are found in every case of FUMHD and can confirm the diagnosis alone, and variable features to help ensure that cases of FUMHD are not missed. The constant features include fever, acute onset of generalized ulceronecrotic papules and plaques, a course that is rapid and progressive (without a tendency for spontaneous resolution), and histopathology that is consistent with PLEVA. The variable features include history of PLEVA, involvement of mucous membranes, and systemic involvement.²

No single unifying treatment modality for all cases of FUMHD has been described. Immunosuppressive drugs (eg, systemic steroids, methotrexate), antibiotics, antivirals, phototherapy, intravenous immunoglobulin, and dapsone have been tried in patients with FUMHD.² Combination therapy with an oral medication such as erythromycin or methotrexate and psoralen plus UVA may be effective for FUMHD.³ Additionally, some authors believe that patients with FUMHD should be treated similar to burn victims with intensive supportive care.²

The etiology of PLEVA is unknown, but it is presumed to be associated with an effector cytotoxic T-cell response to either an infectious agent or a drug.¹¹Three studies have shown that most PLEVA cases (100% [3/3]; 65% [13/20]; and 57% [8/14]) demonstrate T-cell clonality,^12-14 and some have suggested that PLEVA may be a T-cell lymphoproliferative disorder.^12,13 Additionally, in a case report of 2 children with PLEVA who progressed to cutaneous T-cell lymphoma, the authors suggested that PLEVA may be related to nonaggressive cutaneous T-cell lymphoma.¹⁵ Of note, T-cell clonality, often found through the analysis of T-cell receptor gene rearrangement, is not an absolute criterion for determining malignancy, as some benign conditions may have clonality.¹⁶ However, in another study, clonality was found in only 1 of 10 cases of PLEVA, suggesting that PLEVA stems from an inflammatory reaction to infectious or other triggering agents.¹⁷

Four cases of FUMHD with monoclonality have been reported,^4,7,8 and some researchers propose that FUMHD may be a subset of cutaneous T-cell lymphoma.⁷ However, 2 other cases of FUMHD did not show monoclonality of T cells,^5,18 suggesting that FUMHD may represent an inflammatory disorder, rather than a lymphoproliferative process of T cells.¹⁸ Given the controversy surrounding the clonality of FUMHD, T-cell gene rearrangement studies were not performed in our case.

To the Editor:

Pityriasis lichenoides is a papulosquamous dermatologic disorder that is characterized by recurrent papules.¹ There is a spectrum of disease in pityriasis lichenoides that includes pityriasis lichenoides et varioliformis acuta (PLEVA) at one end and pityriasis lichenoides chronica at the other. Pityriasis lichenoides et varioliformis acuta is more common in younger individuals and is characterized by erythematous papules that often crust; these lesions resolve over weeks. The lesions of pityriasis lichenoides chronica are characteristically scaly, pink to red-brown papules that tend to resolve over months.¹

Histologically, PLEVA exhibits parakeratosis, interface dermatitis, and a wedge-shaped infiltrate.¹ Necrotic keratinocytes and extravasated erythrocytes also are common features. Additionally, monoclonal T cells may be present in the infiltrate.¹

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare and severe variant of PLEVA. Febrile ulceronecrotic Mucha-Habermann disease is characterized by ulceronecrotic lesions, fever, and systemic symptoms.² Herein, we present a case of FUMHD.

A 57-year-old man presented with an eruption of painful lesions involving the face, trunk, arms, legs, and genitalia of 1 month’s duration. The patient denied oral and ocular involvement. He had soreness and swelling of the arms and legs. A prior 12-day course of prednisone prescribed by a community dermatologist failed to improve the rash. A biopsy performed by a community dermatologist was nondiagnostic. The patient denied fever but did report chills. He had no preceding illness and was not taking new medications. On physical examination, the patient was afebrile and normotensive with innumerable deep-seated pustules and crusted ulcerations on the face, palms, soles, trunk, extremities, and penis (Figures 1 and 2). There was a background morbilliform eruption on the trunk. The ocular and oral mucosae were spared. The upper and lower extremities had pitting edema.

The patient’s alanine aminotransaminase and aspartate aminotransaminase levels were elevated at 55 and 51 U/L, respectively. His white blood cell count was within reference range; however, there was an elevated absolute neutrophil count (8.7×10³/μL). No eosinophilia was noted. Laboratory evaluation showed a positive antimitochondrial antibody, and magnetic resonance imaging showed evidence of steatohepatitis. Punch biopsies from both the morbilliform eruption and a deep-seated pustule showed epidermal necrosis, parakeratosis, necrotic keratinocytes, and a lichenoid infiltrate of lymphocytes at the dermoepidermal interface. In the dermis, there was a wedge-shaped superficial and deep, perivascular infiltrate with extravasated erythrocytes (Figures 3 and 4). Tissue Gram stain was negative for bacteria. Varicella-zoster virus and herpes simplex virus immunostains were negative. Direct immunofluorescence showed colloid bodies, as can be seen in lichenoid dermatitis.

At the next clinic visit, the patient reported a fever of 39.4 °C. After reviewing the patient’s histopathology and clinical picture, along with the presence of fever, a final diagnosis of FUMHD was made. The patient was started on an oral regimen of prednisone 80 mg once daily, minocycline 100 mg twice daily, and methotrexate 15 mg weekly. Unna boots (specialized compression wraps) with triamcinolone acetonide ointment 0.1% were placed weekly until the leg edema and ulcerations healed. He was maintained on methotrexate 15 mg weekly and 5 to 10 mg of prednisone once daily. The patient demonstrated residual scarring, with only rare new papulonodules that did not ulcerate when attempts were made to taper his medications. He was followed for nearly 3 years, with a recurrence of symptoms 2 years and 3 months after initial presentation to the academic dermatology clinic.

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of PLEVA that can present with the rapid appearance of necrotic skin lesions, fever, and systemic manifestations, including pulmonary, gastrointestinal, central nervous system, cardiac, hematologic, and rheumatologic symptoms.^2-4 The evolution from PLEVA to FUMHD ranges from days to weeks, and patientsrarely can have an initial presentation of FUMHD.² The duration of illness has been reported to be 1 to 24 months⁵; however, the length of illness still remains unclear, as many studies of FUMHD are case reports with limited follow-up. Our patient had a disease duration of at least 27 months. The lesions of FUMHD usually are generalized with flexural prominence, and mucosal involvement occurs in approximately one-quarter of cases. Hypertrophic scarring may be seen after the ulcerated lesions heal.² The incidence of FUMHD is higher in men than in women, and it is more common in younger individuals.^2,6 There have been reported fatalities associated with FUMHD, mostly in adults.^2,4

The clinical differential diagnosis for PLEVA includes disseminated herpes zoster, varicella-zoster virus or coxsackievirus infections, lymphomatoid papulosis, angiodestructive lymphoma such as extranodal natural killer/T-cell lymphoma, drug eruption, arthropod bite, erythema multiforme, ecthyma, ecthyma gangrenosum, necrotic folliculitis, and cutaneous small vessel vasculitis. To differentiate between these diagnoses and PLEVA or FUMHD, it is important to take a strong clinical history. For example, for varicella-zoster virus and coxsackievirus infections, exposure history to the viruses and vaccination history for varicella-zoster virus can help elucidate the diagnosis.

Skin biopsy can help differentiate between these entities and PLEVA or FUMHD. The histopathology of a nonulcerated lesion of FUMHD shows parakeratosis, spongiosis, and lymphocyte exocytosis, as well as lymphocytic vasculitis—findings commonly seen in PLEVA. With the ulceronecrotic lesions of FUMHD, epidermal necrosis and ulceration can be seen microscopically.² Although skin biopsy is not absolutely necessary for making the diagnosis of PLEVA, it can be helpful.³ However, given the dramatic and extreme clinical impression with an extensive differential diagnosis that includes disorders ranging from infectious to neoplastic, biopsy of FUMHD with clinicopathologic correlation often is required.

It is important to avoid biopsying ulcerated lesions of FUMHD, as the histopathologic findings are more likely to be nonspecific. Additionally, nonspecific features often are seen with immunohistochemistry; abnormal laboratory testing may be seen in FUMHD, but there is no specific test to diagnose FUMHD.² Finally, a predominantly CD8⁺ cell infiltrate was seen in 4 of 6 cases of FUMHD, with 2 cases showing a mixed infiltrate of CD8⁺ and CD4⁺ cells.^5,7-10

Although no unified diagnostic criterion exists for FUMHD, Nofal et al² proposed criteria comprised of constant features, which are found in every case of FUMHD and can confirm the diagnosis alone, and variable features to help ensure that cases of FUMHD are not missed. The constant features include fever, acute onset of generalized ulceronecrotic papules and plaques, a course that is rapid and progressive (without a tendency for spontaneous resolution), and histopathology that is consistent with PLEVA. The variable features include history of PLEVA, involvement of mucous membranes, and systemic involvement.²

No single unifying treatment modality for all cases of FUMHD has been described. Immunosuppressive drugs (eg, systemic steroids, methotrexate), antibiotics, antivirals, phototherapy, intravenous immunoglobulin, and dapsone have been tried in patients with FUMHD.² Combination therapy with an oral medication such as erythromycin or methotrexate and psoralen plus UVA may be effective for FUMHD.³ Additionally, some authors believe that patients with FUMHD should be treated similar to burn victims with intensive supportive care.²

The etiology of PLEVA is unknown, but it is presumed to be associated with an effector cytotoxic T-cell response to either an infectious agent or a drug.¹¹Three studies have shown that most PLEVA cases (100% [3/3]; 65% [13/20]; and 57% [8/14]) demonstrate T-cell clonality,^12-14 and some have suggested that PLEVA may be a T-cell lymphoproliferative disorder.^12,13 Additionally, in a case report of 2 children with PLEVA who progressed to cutaneous T-cell lymphoma, the authors suggested that PLEVA may be related to nonaggressive cutaneous T-cell lymphoma.¹⁵ Of note, T-cell clonality, often found through the analysis of T-cell receptor gene rearrangement, is not an absolute criterion for determining malignancy, as some benign conditions may have clonality.¹⁶ However, in another study, clonality was found in only 1 of 10 cases of PLEVA, suggesting that PLEVA stems from an inflammatory reaction to infectious or other triggering agents.¹⁷

Four cases of FUMHD with monoclonality have been reported,^4,7,8 and some researchers propose that FUMHD may be a subset of cutaneous T-cell lymphoma.⁷ However, 2 other cases of FUMHD did not show monoclonality of T cells,^5,18 suggesting that FUMHD may represent an inflammatory disorder, rather than a lymphoproliferative process of T cells.¹⁸ Given the controversy surrounding the clonality of FUMHD, T-cell gene rearrangement studies were not performed in our case.

To the Editor:

Pityriasis lichenoides is a papulosquamous dermatologic disorder that is characterized by recurrent papules.¹ There is a spectrum of disease in pityriasis lichenoides that includes pityriasis lichenoides et varioliformis acuta (PLEVA) at one end and pityriasis lichenoides chronica at the other. Pityriasis lichenoides et varioliformis acuta is more common in younger individuals and is characterized by erythematous papules that often crust; these lesions resolve over weeks. The lesions of pityriasis lichenoides chronica are characteristically scaly, pink to red-brown papules that tend to resolve over months.¹

Histologically, PLEVA exhibits parakeratosis, interface dermatitis, and a wedge-shaped infiltrate.¹ Necrotic keratinocytes and extravasated erythrocytes also are common features. Additionally, monoclonal T cells may be present in the infiltrate.¹

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare and severe variant of PLEVA. Febrile ulceronecrotic Mucha-Habermann disease is characterized by ulceronecrotic lesions, fever, and systemic symptoms.² Herein, we present a case of FUMHD.

A 57-year-old man presented with an eruption of painful lesions involving the face, trunk, arms, legs, and genitalia of 1 month’s duration. The patient denied oral and ocular involvement. He had soreness and swelling of the arms and legs. A prior 12-day course of prednisone prescribed by a community dermatologist failed to improve the rash. A biopsy performed by a community dermatologist was nondiagnostic. The patient denied fever but did report chills. He had no preceding illness and was not taking new medications. On physical examination, the patient was afebrile and normotensive with innumerable deep-seated pustules and crusted ulcerations on the face, palms, soles, trunk, extremities, and penis (Figures 1 and 2). There was a background morbilliform eruption on the trunk. The ocular and oral mucosae were spared. The upper and lower extremities had pitting edema.

The patient’s alanine aminotransaminase and aspartate aminotransaminase levels were elevated at 55 and 51 U/L, respectively. His white blood cell count was within reference range; however, there was an elevated absolute neutrophil count (8.7×10³/μL). No eosinophilia was noted. Laboratory evaluation showed a positive antimitochondrial antibody, and magnetic resonance imaging showed evidence of steatohepatitis. Punch biopsies from both the morbilliform eruption and a deep-seated pustule showed epidermal necrosis, parakeratosis, necrotic keratinocytes, and a lichenoid infiltrate of lymphocytes at the dermoepidermal interface. In the dermis, there was a wedge-shaped superficial and deep, perivascular infiltrate with extravasated erythrocytes (Figures 3 and 4). Tissue Gram stain was negative for bacteria. Varicella-zoster virus and herpes simplex virus immunostains were negative. Direct immunofluorescence showed colloid bodies, as can be seen in lichenoid dermatitis.

At the next clinic visit, the patient reported a fever of 39.4 °C. After reviewing the patient’s histopathology and clinical picture, along with the presence of fever, a final diagnosis of FUMHD was made. The patient was started on an oral regimen of prednisone 80 mg once daily, minocycline 100 mg twice daily, and methotrexate 15 mg weekly. Unna boots (specialized compression wraps) with triamcinolone acetonide ointment 0.1% were placed weekly until the leg edema and ulcerations healed. He was maintained on methotrexate 15 mg weekly and 5 to 10 mg of prednisone once daily. The patient demonstrated residual scarring, with only rare new papulonodules that did not ulcerate when attempts were made to taper his medications. He was followed for nearly 3 years, with a recurrence of symptoms 2 years and 3 months after initial presentation to the academic dermatology clinic.

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of PLEVA that can present with the rapid appearance of necrotic skin lesions, fever, and systemic manifestations, including pulmonary, gastrointestinal, central nervous system, cardiac, hematologic, and rheumatologic symptoms.^2-4 The evolution from PLEVA to FUMHD ranges from days to weeks, and patientsrarely can have an initial presentation of FUMHD.² The duration of illness has been reported to be 1 to 24 months⁵; however, the length of illness still remains unclear, as many studies of FUMHD are case reports with limited follow-up. Our patient had a disease duration of at least 27 months. The lesions of FUMHD usually are generalized with flexural prominence, and mucosal involvement occurs in approximately one-quarter of cases. Hypertrophic scarring may be seen after the ulcerated lesions heal.² The incidence of FUMHD is higher in men than in women, and it is more common in younger individuals.^2,6 There have been reported fatalities associated with FUMHD, mostly in adults.^2,4

The clinical differential diagnosis for PLEVA includes disseminated herpes zoster, varicella-zoster virus or coxsackievirus infections, lymphomatoid papulosis, angiodestructive lymphoma such as extranodal natural killer/T-cell lymphoma, drug eruption, arthropod bite, erythema multiforme, ecthyma, ecthyma gangrenosum, necrotic folliculitis, and cutaneous small vessel vasculitis. To differentiate between these diagnoses and PLEVA or FUMHD, it is important to take a strong clinical history. For example, for varicella-zoster virus and coxsackievirus infections, exposure history to the viruses and vaccination history for varicella-zoster virus can help elucidate the diagnosis.

Skin biopsy can help differentiate between these entities and PLEVA or FUMHD. The histopathology of a nonulcerated lesion of FUMHD shows parakeratosis, spongiosis, and lymphocyte exocytosis, as well as lymphocytic vasculitis—findings commonly seen in PLEVA. With the ulceronecrotic lesions of FUMHD, epidermal necrosis and ulceration can be seen microscopically.² Although skin biopsy is not absolutely necessary for making the diagnosis of PLEVA, it can be helpful.³ However, given the dramatic and extreme clinical impression with an extensive differential diagnosis that includes disorders ranging from infectious to neoplastic, biopsy of FUMHD with clinicopathologic correlation often is required.

It is important to avoid biopsying ulcerated lesions of FUMHD, as the histopathologic findings are more likely to be nonspecific. Additionally, nonspecific features often are seen with immunohistochemistry; abnormal laboratory testing may be seen in FUMHD, but there is no specific test to diagnose FUMHD.² Finally, a predominantly CD8⁺ cell infiltrate was seen in 4 of 6 cases of FUMHD, with 2 cases showing a mixed infiltrate of CD8⁺ and CD4⁺ cells.^5,7-10

Although no unified diagnostic criterion exists for FUMHD, Nofal et al² proposed criteria comprised of constant features, which are found in every case of FUMHD and can confirm the diagnosis alone, and variable features to help ensure that cases of FUMHD are not missed. The constant features include fever, acute onset of generalized ulceronecrotic papules and plaques, a course that is rapid and progressive (without a tendency for spontaneous resolution), and histopathology that is consistent with PLEVA. The variable features include history of PLEVA, involvement of mucous membranes, and systemic involvement.²

No single unifying treatment modality for all cases of FUMHD has been described. Immunosuppressive drugs (eg, systemic steroids, methotrexate), antibiotics, antivirals, phototherapy, intravenous immunoglobulin, and dapsone have been tried in patients with FUMHD.² Combination therapy with an oral medication such as erythromycin or methotrexate and psoralen plus UVA may be effective for FUMHD.³ Additionally, some authors believe that patients with FUMHD should be treated similar to burn victims with intensive supportive care.²

The etiology of PLEVA is unknown, but it is presumed to be associated with an effector cytotoxic T-cell response to either an infectious agent or a drug.¹¹Three studies have shown that most PLEVA cases (100% [3/3]; 65% [13/20]; and 57% [8/14]) demonstrate T-cell clonality,^12-14 and some have suggested that PLEVA may be a T-cell lymphoproliferative disorder.^12,13 Additionally, in a case report of 2 children with PLEVA who progressed to cutaneous T-cell lymphoma, the authors suggested that PLEVA may be related to nonaggressive cutaneous T-cell lymphoma.¹⁵ Of note, T-cell clonality, often found through the analysis of T-cell receptor gene rearrangement, is not an absolute criterion for determining malignancy, as some benign conditions may have clonality.¹⁶ However, in another study, clonality was found in only 1 of 10 cases of PLEVA, suggesting that PLEVA stems from an inflammatory reaction to infectious or other triggering agents.¹⁷

Four cases of FUMHD with monoclonality have been reported,^4,7,8 and some researchers propose that FUMHD may be a subset of cutaneous T-cell lymphoma.⁷ However, 2 other cases of FUMHD did not show monoclonality of T cells,^5,18 suggesting that FUMHD may represent an inflammatory disorder, rather than a lymphoproliferative process of T cells.¹⁸ Given the controversy surrounding the clonality of FUMHD, T-cell gene rearrangement studies were not performed in our case.

Along with long-standing concerns about immunodeficiency and use of immunosuppressive medication in people with rheumatoid arthritis (RA) are juxtaposed concerns about their additional risk of COVID-19 during the pandemic. Several studies have reported a high risk of severe COVID-19 outcomes in people with rheumatic disease, though few have compared this risk to the general population. This cohort study by Wang et al.¹ examines the risk of COVID-19 in people with RA compared to people with OA and the general population based on an electronic medical record database in the UK. The rate of COVID-19 was higher among people with RA than the general population, with a hazard ratio of 1.42 for confirmed COVID-19 cases, while the rate among people with OA was not increased. This finding confirms suspicions, though, due to the study design, it does not lend additional insight into nuances given the lack of information about RA treatment and activity as in prior studies.

Also of concern in the midst of the pandemic is the effect of RA and its treatment on response to vaccines against SARS-CoV-2. The rapid development of mRNA vaccines has been a boon, but research on vaccine response in people with rheumatic disease has suggested that certain medications can impact antibody formation. Iancovici et al.² examined antibody and B cell responses after vaccination in people with RA being treated with Janus kinase (JAK)-inhibitors or tumor necrosis factor (TNF)-inhibitors and in healthy volunteers. Though the study is flawed as responses were not assessed at the same timepoint after vaccination in all subjects and limited due to the heterogeneity of treatment and small numbers of subjects, antibody production and other assays were decreased in RA subjects, suggesting reduced humoral immunity. Whether a pause in JAK inhibitor treatment, as recommended by the American College of Rheumatology, makes an appreciable difference in these assessments of vaccine response is as yet unknown. Further, given the limited data, it is unclear whether having RA on its own, rather than the treatments involved, was the causative factor. Research is already underway on SARS-CoV-2 vaccine response in people with RA and other rheumatic diseases, but studies such as these also imply a relative immunodeficiency due to the diseases and their treatment that could extend to other vaccines or infections.

In addition to impacts on SARS-CoV-2 vaccine response, treatment with JAK inhibitors is known to increase risk of herpes zoster (HZ). A post hoc analysis of pooled data from 21 RA and 3 psoriatic arthritis (PsA) tofacitinib trials by Winthrop et al.³ evaluated the number and severity of HZ infections. Interestingly, HZ infections occurred more frequently in participants in the RA clinical trials, with about 11% having an infection compared to 5% in the PsA studies, once again highlighting a potential immunodeficiency particular to people with RA. Most patients had mild to moderate infections, but a small proportion of patients (<5%) had severe infections. Given the possibility of a reduced vaccine response, though unknown, after HZ vaccination in people with RA, consideration should be given not only to vaccination prior to initiation of JAK inhibitor therapy, but to assessment of vaccine efficacy and the ideal dosing schedules in these patients.

References

1. Wang Y et al. Increased risk of COVID-19 in patients with rheumatoid arthritis: a general population-based cohort study. Arthritis Care Res (Hoboken) 2021(Dec 7). 
2. Iancovici L et al. Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination. Rheumatology (Oxford). 2021:keab879 (Nov 25).
3. Winthrop KL et al. Clinical management of herpes zoster in patients with rheumatoid arthritis or psoriatic arthritis receiving tofacitinib treatment. Rheumatol Ther. 2021 (Dec 6).

Along with long-standing concerns about immunodeficiency and use of immunosuppressive medication in people with rheumatoid arthritis (RA) are juxtaposed concerns about their additional risk of COVID-19 during the pandemic. Several studies have reported a high risk of severe COVID-19 outcomes in people with rheumatic disease, though few have compared this risk to the general population. This cohort study by Wang et al.¹ examines the risk of COVID-19 in people with RA compared to people with OA and the general population based on an electronic medical record database in the UK. The rate of COVID-19 was higher among people with RA than the general population, with a hazard ratio of 1.42 for confirmed COVID-19 cases, while the rate among people with OA was not increased. This finding confirms suspicions, though, due to the study design, it does not lend additional insight into nuances given the lack of information about RA treatment and activity as in prior studies.

Also of concern in the midst of the pandemic is the effect of RA and its treatment on response to vaccines against SARS-CoV-2. The rapid development of mRNA vaccines has been a boon, but research on vaccine response in people with rheumatic disease has suggested that certain medications can impact antibody formation. Iancovici et al.² examined antibody and B cell responses after vaccination in people with RA being treated with Janus kinase (JAK)-inhibitors or tumor necrosis factor (TNF)-inhibitors and in healthy volunteers. Though the study is flawed as responses were not assessed at the same timepoint after vaccination in all subjects and limited due to the heterogeneity of treatment and small numbers of subjects, antibody production and other assays were decreased in RA subjects, suggesting reduced humoral immunity. Whether a pause in JAK inhibitor treatment, as recommended by the American College of Rheumatology, makes an appreciable difference in these assessments of vaccine response is as yet unknown. Further, given the limited data, it is unclear whether having RA on its own, rather than the treatments involved, was the causative factor. Research is already underway on SARS-CoV-2 vaccine response in people with RA and other rheumatic diseases, but studies such as these also imply a relative immunodeficiency due to the diseases and their treatment that could extend to other vaccines or infections.

In addition to impacts on SARS-CoV-2 vaccine response, treatment with JAK inhibitors is known to increase risk of herpes zoster (HZ). A post hoc analysis of pooled data from 21 RA and 3 psoriatic arthritis (PsA) tofacitinib trials by Winthrop et al.³ evaluated the number and severity of HZ infections. Interestingly, HZ infections occurred more frequently in participants in the RA clinical trials, with about 11% having an infection compared to 5% in the PsA studies, once again highlighting a potential immunodeficiency particular to people with RA. Most patients had mild to moderate infections, but a small proportion of patients (<5%) had severe infections. Given the possibility of a reduced vaccine response, though unknown, after HZ vaccination in people with RA, consideration should be given not only to vaccination prior to initiation of JAK inhibitor therapy, but to assessment of vaccine efficacy and the ideal dosing schedules in these patients.

References

1. Wang Y et al. Increased risk of COVID-19 in patients with rheumatoid arthritis: a general population-based cohort study. Arthritis Care Res (Hoboken) 2021(Dec 7). 
2. Iancovici L et al. Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination. Rheumatology (Oxford). 2021:keab879 (Nov 25).
3. Winthrop KL et al. Clinical management of herpes zoster in patients with rheumatoid arthritis or psoriatic arthritis receiving tofacitinib treatment. Rheumatol Ther. 2021 (Dec 6).

Along with long-standing concerns about immunodeficiency and use of immunosuppressive medication in people with rheumatoid arthritis (RA) are juxtaposed concerns about their additional risk of COVID-19 during the pandemic. Several studies have reported a high risk of severe COVID-19 outcomes in people with rheumatic disease, though few have compared this risk to the general population. This cohort study by Wang et al.¹ examines the risk of COVID-19 in people with RA compared to people with OA and the general population based on an electronic medical record database in the UK. The rate of COVID-19 was higher among people with RA than the general population, with a hazard ratio of 1.42 for confirmed COVID-19 cases, while the rate among people with OA was not increased. This finding confirms suspicions, though, due to the study design, it does not lend additional insight into nuances given the lack of information about RA treatment and activity as in prior studies.

Also of concern in the midst of the pandemic is the effect of RA and its treatment on response to vaccines against SARS-CoV-2. The rapid development of mRNA vaccines has been a boon, but research on vaccine response in people with rheumatic disease has suggested that certain medications can impact antibody formation. Iancovici et al.² examined antibody and B cell responses after vaccination in people with RA being treated with Janus kinase (JAK)-inhibitors or tumor necrosis factor (TNF)-inhibitors and in healthy volunteers. Though the study is flawed as responses were not assessed at the same timepoint after vaccination in all subjects and limited due to the heterogeneity of treatment and small numbers of subjects, antibody production and other assays were decreased in RA subjects, suggesting reduced humoral immunity. Whether a pause in JAK inhibitor treatment, as recommended by the American College of Rheumatology, makes an appreciable difference in these assessments of vaccine response is as yet unknown. Further, given the limited data, it is unclear whether having RA on its own, rather than the treatments involved, was the causative factor. Research is already underway on SARS-CoV-2 vaccine response in people with RA and other rheumatic diseases, but studies such as these also imply a relative immunodeficiency due to the diseases and their treatment that could extend to other vaccines or infections.

In addition to impacts on SARS-CoV-2 vaccine response, treatment with JAK inhibitors is known to increase risk of herpes zoster (HZ). A post hoc analysis of pooled data from 21 RA and 3 psoriatic arthritis (PsA) tofacitinib trials by Winthrop et al.³ evaluated the number and severity of HZ infections. Interestingly, HZ infections occurred more frequently in participants in the RA clinical trials, with about 11% having an infection compared to 5% in the PsA studies, once again highlighting a potential immunodeficiency particular to people with RA. Most patients had mild to moderate infections, but a small proportion of patients (<5%) had severe infections. Given the possibility of a reduced vaccine response, though unknown, after HZ vaccination in people with RA, consideration should be given not only to vaccination prior to initiation of JAK inhibitor therapy, but to assessment of vaccine efficacy and the ideal dosing schedules in these patients.

References

1. Wang Y et al. Increased risk of COVID-19 in patients with rheumatoid arthritis: a general population-based cohort study. Arthritis Care Res (Hoboken) 2021(Dec 7). 
2. Iancovici L et al. Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination. Rheumatology (Oxford). 2021:keab879 (Nov 25).
3. Winthrop KL et al. Clinical management of herpes zoster in patients with rheumatoid arthritis or psoriatic arthritis receiving tofacitinib treatment. Rheumatol Ther. 2021 (Dec 6).

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Fascia lata autologous transobturator midurethral sling

• Strategies for safe dissection of cervical fibroids during hysterectomy

• Concomitant laparoscopic and vaginal excision of duplicated collecting system

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Fascia lata autologous transobturator midurethral sling

• Strategies for safe dissection of cervical fibroids during hysterectomy

• Concomitant laparoscopic and vaginal excision of duplicated collecting system

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Fascia lata autologous transobturator midurethral sling

• Strategies for safe dissection of cervical fibroids during hysterectomy

• Concomitant laparoscopic and vaginal excision of duplicated collecting system

As of 2018, the mean dermatologist to population ratio in the United States was 1.10 per 100,000 people, highlighting a shortage of dermatologists that is only predicted to increase in coming years.^1-4 This undersupply is fueled by both an increasing burden of dermatologic disease and population growth.⁴ Without readily available access to dermatologic care, many patients are left waiting for weeks to see a dermatologist, depending on geographic region.^5-7 It is not simply patients who perceive wait times to be prolonged; approximately half of dermatologists surveyed by the American Academy of Dermatology (AAD) reported an undersupply of dermatologists in their communities, a finding that strongly correlated with patient wait times.² Ensuring the dermatologic workforce is sufficient to fulfill patient needs requires innovation of current practice models. To address this unmet demand, many practices have begun incorporating physician extenders, a term that encompasses physicians not board certified in dermatology, physician assistants, and nurse practitioners.⁷ The evolving landscape of the dermatologic workforce raises questions about future practice models and patient outcomes.

Scope of Practice for Physician Extenders

In practice, the role of physician extenders is highly variable. Legislation involving the scope of practice for physician extenders constantly is changing and varies by state. As of November 2021, 24 states and the District of Columbia permit nurse practitioners “full practice” authority to triage patients, interpret diagnostic tests, and prescribe treatments without physician oversight, including controlled substances.^8,9 Even in states with “reduced practice” and “restricted practice” paradigms, which necessitate physician oversight, there remains ambiguity. Across the country, state regulatory bodies differ in statues governing licensing requirements, accessibility of the supervising physician, and ultimately culpability in the case of patient harm. Lack of consensus guidelines that clearly define roles and responsibilities has kindled controversy regarding extent of autonomy and liability for adverse outcomes.^10,11

With respect to procedures, the AAD has explicitly recommended that “only active and properly licensed doctors of medicine and osteopathy shall engage in the practice of medicine” but that “under appropriate circumstances, a physician may delegate certain procedures and services to appropriately trained nonphysician office personnel.”¹² This statement does not refer to or explicitly list the procedures that are appropriate for delegation to nonphysician personnel, and there is wide variability in how this recommendation is applied in daily practice. As it was originally intended, the AAD’s “Ethics in Medical Practice” position statement indicated that dermatologists must directly oversee physician extenders, a responsibility that is defined as being “present on-site, immediately available and able to respond promptly” to issues arising during the provision of health care services.¹²

Adverse Events From Cosmetic Procedures

The American Society for Dermatologic Surgery has documented a steady growth in the demand for cosmetic, medical, and surgical services,¹³ a trend that has heralded an increase in the number of procedures performed by physician extenders.^14,15 One study contrasted the risk for adverse events following minimally invasive cosmetic procedures performed by physicians or nonphysicians. Of 2116 patients surveyed, 50 adverse events were documented.¹⁴ The cohort treated by nonphysicians experienced a higher incidence of laser burns and dyspigmentation, and the use of improper technique was the most frequently implicated cause of developing an adverse event. Approximately 24.6% of American Society for Dermatologic Surgery members reported treating 10 or more complications of cosmetic procedures performed by nonphysicians.¹⁴ Beyond laser burns and dyspigmentation, this wide range of complications included inappropriately placed filler product, facial drooping, and scarring. These studies highlight the need for further investigation into the outcomes of procedures performed by physician extenders.

Training of Physician Extenders

Even with medical management, emphasis on proper training of personnel is key and remains a legitimate concern. The training of physician extenders in dermatology differs greatly by location; while some physician extenders operate under meticulous guidance and thus can expand their skill set, other physician extenders shadow dermatologists for an arbitrary amount of time before being thrust into practice.¹⁰ It would be a disservice to both patients and nonphysician providers alike to conflate the latter regimen with the 4 years of medical school, 1 year of internship, and 3 years of rigorous specialized dermatologic training that physicians undergo.

This stark discrepancy between the training of physicians and physician extenders raises difficult questions about the patient’s right to make an informed decision regarding how they receive health care. Indeed, the casually regulated autonomous practice of some nonphysician providers has ignited public shock and ire.¹¹

Reducing Health Care Expenditures

As legislatures deliberate over expanding scope of practice, policies should be based on evidence that prioritizes patient safety. In the appropriate setting, physician extenders can be instrumental to mitigating health care disparities; the use of physician extenders can diminish wait times for patients with routine visits for stable dermatologic disease.¹⁶ Moreover, reducing health care expenditures often is cited as a major benefit of increased utilization of physician extenders.¹⁴ It stands to reason that compensation of nonphysician providers is less expensive for a practice compared with physicians. Physician extenders participating in the management of stable chronic conditions or mild acute conditions may be cost-efficient in these circumstances; however, evidence suggests that physician extenders may incur greater costs than physicians with respect to the utilization of diagnostic tests or prescribing medications. For example, several studies have documented a substantial difference in the number of biopsies needed per malignant neoplasm by physicians compared to physician extenders.^17-19 Particularly in patients younger than 65 years and in patients without history of skin cancer, physician extenders had to perform a greater number of biopsies to diagnose malignant neoplasms vs physicians.¹⁸ In addition to increased utilization of diagnostic tests, nonphysician providers more frequently prescribe medications of varying classes.^20-22 Whether in outpatient offices, emergency departments, or hospital clinics, physician extenders more frequently prescribe antibiotics, which has concerning implications for antibiotic stewardship.^20,21 In states with independent prescription authority, physician extenders are more than 20 times more likely to overprescribeopioids compared to physician extenders in states requiring physician supervision.²³ These findings warrant additional investigation into how prescription patterns vary by provider type and how these differences impact patient outcomes.

Final Thoughts

Improving patient care is inherently a team endeavor, and the contributions of all members of the health care team are critical to success. Engaging physician extenders may help mitigate disparities in dermatologic care, with respect to surveillance of stable chronic conditions or the diagnosis of mild acute diseases. However, the exact scope of practice of physician extenders remains ambiguous, and their training regimens can vary drastically. Therefore, in the interest of patient safety, new patients or medically complex patients (ie, cutaneous lymphomas, nonstable autoimmune connective tissue disease) should be examined and managed by physicians. In either scenario, the patient should be informed of which providers are available and should be integrated into the decision-making process for their care. Through mutual respect, close collaboration, and candid assessments of patient complexity, different parties within the medical team can unite behind the mission to improve patient outcomes and champion equitable access to health care.

As of 2018, the mean dermatologist to population ratio in the United States was 1.10 per 100,000 people, highlighting a shortage of dermatologists that is only predicted to increase in coming years.^1-4 This undersupply is fueled by both an increasing burden of dermatologic disease and population growth.⁴ Without readily available access to dermatologic care, many patients are left waiting for weeks to see a dermatologist, depending on geographic region.^5-7 It is not simply patients who perceive wait times to be prolonged; approximately half of dermatologists surveyed by the American Academy of Dermatology (AAD) reported an undersupply of dermatologists in their communities, a finding that strongly correlated with patient wait times.² Ensuring the dermatologic workforce is sufficient to fulfill patient needs requires innovation of current practice models. To address this unmet demand, many practices have begun incorporating physician extenders, a term that encompasses physicians not board certified in dermatology, physician assistants, and nurse practitioners.⁷ The evolving landscape of the dermatologic workforce raises questions about future practice models and patient outcomes.

Scope of Practice for Physician Extenders

In practice, the role of physician extenders is highly variable. Legislation involving the scope of practice for physician extenders constantly is changing and varies by state. As of November 2021, 24 states and the District of Columbia permit nurse practitioners “full practice” authority to triage patients, interpret diagnostic tests, and prescribe treatments without physician oversight, including controlled substances.^8,9 Even in states with “reduced practice” and “restricted practice” paradigms, which necessitate physician oversight, there remains ambiguity. Across the country, state regulatory bodies differ in statues governing licensing requirements, accessibility of the supervising physician, and ultimately culpability in the case of patient harm. Lack of consensus guidelines that clearly define roles and responsibilities has kindled controversy regarding extent of autonomy and liability for adverse outcomes.^10,11

With respect to procedures, the AAD has explicitly recommended that “only active and properly licensed doctors of medicine and osteopathy shall engage in the practice of medicine” but that “under appropriate circumstances, a physician may delegate certain procedures and services to appropriately trained nonphysician office personnel.”¹² This statement does not refer to or explicitly list the procedures that are appropriate for delegation to nonphysician personnel, and there is wide variability in how this recommendation is applied in daily practice. As it was originally intended, the AAD’s “Ethics in Medical Practice” position statement indicated that dermatologists must directly oversee physician extenders, a responsibility that is defined as being “present on-site, immediately available and able to respond promptly” to issues arising during the provision of health care services.¹²

Adverse Events From Cosmetic Procedures

The American Society for Dermatologic Surgery has documented a steady growth in the demand for cosmetic, medical, and surgical services,¹³ a trend that has heralded an increase in the number of procedures performed by physician extenders.^14,15 One study contrasted the risk for adverse events following minimally invasive cosmetic procedures performed by physicians or nonphysicians. Of 2116 patients surveyed, 50 adverse events were documented.¹⁴ The cohort treated by nonphysicians experienced a higher incidence of laser burns and dyspigmentation, and the use of improper technique was the most frequently implicated cause of developing an adverse event. Approximately 24.6% of American Society for Dermatologic Surgery members reported treating 10 or more complications of cosmetic procedures performed by nonphysicians.¹⁴ Beyond laser burns and dyspigmentation, this wide range of complications included inappropriately placed filler product, facial drooping, and scarring. These studies highlight the need for further investigation into the outcomes of procedures performed by physician extenders.

Training of Physician Extenders

Even with medical management, emphasis on proper training of personnel is key and remains a legitimate concern. The training of physician extenders in dermatology differs greatly by location; while some physician extenders operate under meticulous guidance and thus can expand their skill set, other physician extenders shadow dermatologists for an arbitrary amount of time before being thrust into practice.¹⁰ It would be a disservice to both patients and nonphysician providers alike to conflate the latter regimen with the 4 years of medical school, 1 year of internship, and 3 years of rigorous specialized dermatologic training that physicians undergo.

This stark discrepancy between the training of physicians and physician extenders raises difficult questions about the patient’s right to make an informed decision regarding how they receive health care. Indeed, the casually regulated autonomous practice of some nonphysician providers has ignited public shock and ire.¹¹

Reducing Health Care Expenditures

As legislatures deliberate over expanding scope of practice, policies should be based on evidence that prioritizes patient safety. In the appropriate setting, physician extenders can be instrumental to mitigating health care disparities; the use of physician extenders can diminish wait times for patients with routine visits for stable dermatologic disease.¹⁶ Moreover, reducing health care expenditures often is cited as a major benefit of increased utilization of physician extenders.¹⁴ It stands to reason that compensation of nonphysician providers is less expensive for a practice compared with physicians. Physician extenders participating in the management of stable chronic conditions or mild acute conditions may be cost-efficient in these circumstances; however, evidence suggests that physician extenders may incur greater costs than physicians with respect to the utilization of diagnostic tests or prescribing medications. For example, several studies have documented a substantial difference in the number of biopsies needed per malignant neoplasm by physicians compared to physician extenders.^17-19 Particularly in patients younger than 65 years and in patients without history of skin cancer, physician extenders had to perform a greater number of biopsies to diagnose malignant neoplasms vs physicians.¹⁸ In addition to increased utilization of diagnostic tests, nonphysician providers more frequently prescribe medications of varying classes.^20-22 Whether in outpatient offices, emergency departments, or hospital clinics, physician extenders more frequently prescribe antibiotics, which has concerning implications for antibiotic stewardship.^20,21 In states with independent prescription authority, physician extenders are more than 20 times more likely to overprescribeopioids compared to physician extenders in states requiring physician supervision.²³ These findings warrant additional investigation into how prescription patterns vary by provider type and how these differences impact patient outcomes.

Final Thoughts

Improving patient care is inherently a team endeavor, and the contributions of all members of the health care team are critical to success. Engaging physician extenders may help mitigate disparities in dermatologic care, with respect to surveillance of stable chronic conditions or the diagnosis of mild acute diseases. However, the exact scope of practice of physician extenders remains ambiguous, and their training regimens can vary drastically. Therefore, in the interest of patient safety, new patients or medically complex patients (ie, cutaneous lymphomas, nonstable autoimmune connective tissue disease) should be examined and managed by physicians. In either scenario, the patient should be informed of which providers are available and should be integrated into the decision-making process for their care. Through mutual respect, close collaboration, and candid assessments of patient complexity, different parties within the medical team can unite behind the mission to improve patient outcomes and champion equitable access to health care.

As of 2018, the mean dermatologist to population ratio in the United States was 1.10 per 100,000 people, highlighting a shortage of dermatologists that is only predicted to increase in coming years.^1-4 This undersupply is fueled by both an increasing burden of dermatologic disease and population growth.⁴ Without readily available access to dermatologic care, many patients are left waiting for weeks to see a dermatologist, depending on geographic region.^5-7 It is not simply patients who perceive wait times to be prolonged; approximately half of dermatologists surveyed by the American Academy of Dermatology (AAD) reported an undersupply of dermatologists in their communities, a finding that strongly correlated with patient wait times.² Ensuring the dermatologic workforce is sufficient to fulfill patient needs requires innovation of current practice models. To address this unmet demand, many practices have begun incorporating physician extenders, a term that encompasses physicians not board certified in dermatology, physician assistants, and nurse practitioners.⁷ The evolving landscape of the dermatologic workforce raises questions about future practice models and patient outcomes.

Scope of Practice for Physician Extenders

In practice, the role of physician extenders is highly variable. Legislation involving the scope of practice for physician extenders constantly is changing and varies by state. As of November 2021, 24 states and the District of Columbia permit nurse practitioners “full practice” authority to triage patients, interpret diagnostic tests, and prescribe treatments without physician oversight, including controlled substances.^8,9 Even in states with “reduced practice” and “restricted practice” paradigms, which necessitate physician oversight, there remains ambiguity. Across the country, state regulatory bodies differ in statues governing licensing requirements, accessibility of the supervising physician, and ultimately culpability in the case of patient harm. Lack of consensus guidelines that clearly define roles and responsibilities has kindled controversy regarding extent of autonomy and liability for adverse outcomes.^10,11

With respect to procedures, the AAD has explicitly recommended that “only active and properly licensed doctors of medicine and osteopathy shall engage in the practice of medicine” but that “under appropriate circumstances, a physician may delegate certain procedures and services to appropriately trained nonphysician office personnel.”¹² This statement does not refer to or explicitly list the procedures that are appropriate for delegation to nonphysician personnel, and there is wide variability in how this recommendation is applied in daily practice. As it was originally intended, the AAD’s “Ethics in Medical Practice” position statement indicated that dermatologists must directly oversee physician extenders, a responsibility that is defined as being “present on-site, immediately available and able to respond promptly” to issues arising during the provision of health care services.¹²

Adverse Events From Cosmetic Procedures

The American Society for Dermatologic Surgery has documented a steady growth in the demand for cosmetic, medical, and surgical services,¹³ a trend that has heralded an increase in the number of procedures performed by physician extenders.^14,15 One study contrasted the risk for adverse events following minimally invasive cosmetic procedures performed by physicians or nonphysicians. Of 2116 patients surveyed, 50 adverse events were documented.¹⁴ The cohort treated by nonphysicians experienced a higher incidence of laser burns and dyspigmentation, and the use of improper technique was the most frequently implicated cause of developing an adverse event. Approximately 24.6% of American Society for Dermatologic Surgery members reported treating 10 or more complications of cosmetic procedures performed by nonphysicians.¹⁴ Beyond laser burns and dyspigmentation, this wide range of complications included inappropriately placed filler product, facial drooping, and scarring. These studies highlight the need for further investigation into the outcomes of procedures performed by physician extenders.

Training of Physician Extenders

Even with medical management, emphasis on proper training of personnel is key and remains a legitimate concern. The training of physician extenders in dermatology differs greatly by location; while some physician extenders operate under meticulous guidance and thus can expand their skill set, other physician extenders shadow dermatologists for an arbitrary amount of time before being thrust into practice.¹⁰ It would be a disservice to both patients and nonphysician providers alike to conflate the latter regimen with the 4 years of medical school, 1 year of internship, and 3 years of rigorous specialized dermatologic training that physicians undergo.

This stark discrepancy between the training of physicians and physician extenders raises difficult questions about the patient’s right to make an informed decision regarding how they receive health care. Indeed, the casually regulated autonomous practice of some nonphysician providers has ignited public shock and ire.¹¹

Reducing Health Care Expenditures

As legislatures deliberate over expanding scope of practice, policies should be based on evidence that prioritizes patient safety. In the appropriate setting, physician extenders can be instrumental to mitigating health care disparities; the use of physician extenders can diminish wait times for patients with routine visits for stable dermatologic disease.¹⁶ Moreover, reducing health care expenditures often is cited as a major benefit of increased utilization of physician extenders.¹⁴ It stands to reason that compensation of nonphysician providers is less expensive for a practice compared with physicians. Physician extenders participating in the management of stable chronic conditions or mild acute conditions may be cost-efficient in these circumstances; however, evidence suggests that physician extenders may incur greater costs than physicians with respect to the utilization of diagnostic tests or prescribing medications. For example, several studies have documented a substantial difference in the number of biopsies needed per malignant neoplasm by physicians compared to physician extenders.^17-19 Particularly in patients younger than 65 years and in patients without history of skin cancer, physician extenders had to perform a greater number of biopsies to diagnose malignant neoplasms vs physicians.¹⁸ In addition to increased utilization of diagnostic tests, nonphysician providers more frequently prescribe medications of varying classes.^20-22 Whether in outpatient offices, emergency departments, or hospital clinics, physician extenders more frequently prescribe antibiotics, which has concerning implications for antibiotic stewardship.^20,21 In states with independent prescription authority, physician extenders are more than 20 times more likely to overprescribeopioids compared to physician extenders in states requiring physician supervision.²³ These findings warrant additional investigation into how prescription patterns vary by provider type and how these differences impact patient outcomes.

Final Thoughts

Improving patient care is inherently a team endeavor, and the contributions of all members of the health care team are critical to success. Engaging physician extenders may help mitigate disparities in dermatologic care, with respect to surveillance of stable chronic conditions or the diagnosis of mild acute diseases. However, the exact scope of practice of physician extenders remains ambiguous, and their training regimens can vary drastically. Therefore, in the interest of patient safety, new patients or medically complex patients (ie, cutaneous lymphomas, nonstable autoimmune connective tissue disease) should be examined and managed by physicians. In either scenario, the patient should be informed of which providers are available and should be integrated into the decision-making process for their care. Through mutual respect, close collaboration, and candid assessments of patient complexity, different parties within the medical team can unite behind the mission to improve patient outcomes and champion equitable access to health care.

The Diagnosis: Actinomycetoma

Histopathology revealed evidence of an actinomycete organism within the suppuration, consistent with actinomycosis (quiz image [inset]). Given the clinical presentation and histopathologic findings, our patient was diagnosed with actinomycetoma.

Actinomycetoma is an indolent, progressive, subcutaneous infection characterized by a well-known clinical triad of tumefaction/subcutaneous mass, draining sinuses, and an exudate containing grains on microscopy. The sinus tracts are formed from the chronic infectious process that destroys tissue, creating tunnels. This infectious disease of soft tissue is a clinical subset of mycetoma, which is categorized as eumycetoma (fungal) and actinomycetoma (bacterial). Actinomycetoma resembles the behavior of insidious and chronic fungal infections; however, most mycetoma infections are bacterial.^1,2 Actinomycetoma may be confused with actinomycosis, which is caused by Actinomycoses species, commensal organisms commonly located on the teeth and oral mucosa in association with other microorganisms that may pathogenically cause cervicofacial actinomycosis.^3,4 Actinomycetoma can be caused by Nocardia, Streptomyces, and Actinomadura. ^2,5 The foot is the most common location of involvement followed by the thoracic region. It is more common in tropical or equatorial locations and may be contracted through exposure to soil or wood.⁵ Mycetoma is considered a neglected tropical disease by the World Health Organization.1 In tropical countries, this disease may go undiagnosed or untreated for so long that surgical amputation may be the only effective treatment.

Actinomycetoma commonly is identifiable by direct microscopy, Gram stain, or bacterial culture, with Gram stain being more sensitive than bacterial culture.³ It is important to indicate the suspected organism to the microbiology laboratory because common bacterial pathogens are detected within 24 to 48 hours, but the causative microorganism in actinomycetoma may require up to 4 weeks for culture,² leading to possible false negatives due to inadequate culture time.³ Histopathology of actinomycotic infections will demonstrate granulomatous inflammation, focal suppuration, and the presence of grains (ie, a colony of filamentous bacteria in a stellate shaped mass)(quiz image [inset]).

The gold standard of treatment is trimethoprim-sulfamethoxazole for up to several years.^4,5 Amoxicillin–clavulanic acid, dapsone, amikacin, streptomycin, and beta-lactams have been used successfully.^2,5 The treatment course is dependent on clinical severity and location of the disease. The cure rate with appropriate antibiotics can be as high as 90%,^2,5 and thus surgical intervention can be avoided.

In the differential, cutaneous tuberculosis would show tuberculoid granulomas with epithelioid histiocytes with possible caseation on histopathology, typically alongside positive tuberculosis screening. Botryomycosis has a similar clinical presentation of a swollen or indurated lesion with draining sinus tracts, but it less commonly occurs on the trunk. Histopathology also is a close mimic of actinomycetoma with a small grain inside a suppurative infiltrate; however, it has no filamentous bacteria. A foreign body reaction would not histologically present with suppuration or grains, and draining sinuses typically would not be seen on clinical presentation. Sarcoma is a neoplastic process and most commonly would show a proliferation of cells with soft tissue or bone origin on histopathology and not primarily an inflammatory cell process.⁶

The Diagnosis: Actinomycetoma

Histopathology revealed evidence of an actinomycete organism within the suppuration, consistent with actinomycosis (quiz image [inset]). Given the clinical presentation and histopathologic findings, our patient was diagnosed with actinomycetoma.

Actinomycetoma is an indolent, progressive, subcutaneous infection characterized by a well-known clinical triad of tumefaction/subcutaneous mass, draining sinuses, and an exudate containing grains on microscopy. The sinus tracts are formed from the chronic infectious process that destroys tissue, creating tunnels. This infectious disease of soft tissue is a clinical subset of mycetoma, which is categorized as eumycetoma (fungal) and actinomycetoma (bacterial). Actinomycetoma resembles the behavior of insidious and chronic fungal infections; however, most mycetoma infections are bacterial.^1,2 Actinomycetoma may be confused with actinomycosis, which is caused by Actinomycoses species, commensal organisms commonly located on the teeth and oral mucosa in association with other microorganisms that may pathogenically cause cervicofacial actinomycosis.^3,4 Actinomycetoma can be caused by Nocardia, Streptomyces, and Actinomadura. ^2,5 The foot is the most common location of involvement followed by the thoracic region. It is more common in tropical or equatorial locations and may be contracted through exposure to soil or wood.⁵ Mycetoma is considered a neglected tropical disease by the World Health Organization.1 In tropical countries, this disease may go undiagnosed or untreated for so long that surgical amputation may be the only effective treatment.

Actinomycetoma commonly is identifiable by direct microscopy, Gram stain, or bacterial culture, with Gram stain being more sensitive than bacterial culture.³ It is important to indicate the suspected organism to the microbiology laboratory because common bacterial pathogens are detected within 24 to 48 hours, but the causative microorganism in actinomycetoma may require up to 4 weeks for culture,² leading to possible false negatives due to inadequate culture time.³ Histopathology of actinomycotic infections will demonstrate granulomatous inflammation, focal suppuration, and the presence of grains (ie, a colony of filamentous bacteria in a stellate shaped mass)(quiz image [inset]).

The gold standard of treatment is trimethoprim-sulfamethoxazole for up to several years.^4,5 Amoxicillin–clavulanic acid, dapsone, amikacin, streptomycin, and beta-lactams have been used successfully.^2,5 The treatment course is dependent on clinical severity and location of the disease. The cure rate with appropriate antibiotics can be as high as 90%,^2,5 and thus surgical intervention can be avoided.

In the differential, cutaneous tuberculosis would show tuberculoid granulomas with epithelioid histiocytes with possible caseation on histopathology, typically alongside positive tuberculosis screening. Botryomycosis has a similar clinical presentation of a swollen or indurated lesion with draining sinus tracts, but it less commonly occurs on the trunk. Histopathology also is a close mimic of actinomycetoma with a small grain inside a suppurative infiltrate; however, it has no filamentous bacteria. A foreign body reaction would not histologically present with suppuration or grains, and draining sinuses typically would not be seen on clinical presentation. Sarcoma is a neoplastic process and most commonly would show a proliferation of cells with soft tissue or bone origin on histopathology and not primarily an inflammatory cell process.⁶

The Diagnosis: Actinomycetoma

Histopathology revealed evidence of an actinomycete organism within the suppuration, consistent with actinomycosis (quiz image [inset]). Given the clinical presentation and histopathologic findings, our patient was diagnosed with actinomycetoma.

Actinomycetoma is an indolent, progressive, subcutaneous infection characterized by a well-known clinical triad of tumefaction/subcutaneous mass, draining sinuses, and an exudate containing grains on microscopy. The sinus tracts are formed from the chronic infectious process that destroys tissue, creating tunnels. This infectious disease of soft tissue is a clinical subset of mycetoma, which is categorized as eumycetoma (fungal) and actinomycetoma (bacterial). Actinomycetoma resembles the behavior of insidious and chronic fungal infections; however, most mycetoma infections are bacterial.^1,2 Actinomycetoma may be confused with actinomycosis, which is caused by Actinomycoses species, commensal organisms commonly located on the teeth and oral mucosa in association with other microorganisms that may pathogenically cause cervicofacial actinomycosis.^3,4 Actinomycetoma can be caused by Nocardia, Streptomyces, and Actinomadura. ^2,5 The foot is the most common location of involvement followed by the thoracic region. It is more common in tropical or equatorial locations and may be contracted through exposure to soil or wood.⁵ Mycetoma is considered a neglected tropical disease by the World Health Organization.1 In tropical countries, this disease may go undiagnosed or untreated for so long that surgical amputation may be the only effective treatment.

Actinomycetoma commonly is identifiable by direct microscopy, Gram stain, or bacterial culture, with Gram stain being more sensitive than bacterial culture.³ It is important to indicate the suspected organism to the microbiology laboratory because common bacterial pathogens are detected within 24 to 48 hours, but the causative microorganism in actinomycetoma may require up to 4 weeks for culture,² leading to possible false negatives due to inadequate culture time.³ Histopathology of actinomycotic infections will demonstrate granulomatous inflammation, focal suppuration, and the presence of grains (ie, a colony of filamentous bacteria in a stellate shaped mass)(quiz image [inset]).

The gold standard of treatment is trimethoprim-sulfamethoxazole for up to several years.^4,5 Amoxicillin–clavulanic acid, dapsone, amikacin, streptomycin, and beta-lactams have been used successfully.^2,5 The treatment course is dependent on clinical severity and location of the disease. The cure rate with appropriate antibiotics can be as high as 90%,^2,5 and thus surgical intervention can be avoided.

In the differential, cutaneous tuberculosis would show tuberculoid granulomas with epithelioid histiocytes with possible caseation on histopathology, typically alongside positive tuberculosis screening. Botryomycosis has a similar clinical presentation of a swollen or indurated lesion with draining sinus tracts, but it less commonly occurs on the trunk. Histopathology also is a close mimic of actinomycetoma with a small grain inside a suppurative infiltrate; however, it has no filamentous bacteria. A foreign body reaction would not histologically present with suppuration or grains, and draining sinuses typically would not be seen on clinical presentation. Sarcoma is a neoplastic process and most commonly would show a proliferation of cells with soft tissue or bone origin on histopathology and not primarily an inflammatory cell process.⁶