Scott Worswick, MD

To the Editor:

We read with interest the Cutis article by Dobkin et al¹ (Cutis. 2022;109:218-220) regarding guidelines for inpatient and emergency department dermatology consultations. We agree with the authors that dermatology training is lacking in other medical specialties, which makes it challenging for teams to assess the appropriateness of a dermatology consultation in the inpatient setting. Inpatient dermatology consultation can be utilized in a hospital system to aid in rapid and accurate diagnosis, avoid inappropriate therapies, and decrease length of stay² and readmission rates³ while providing education to the primary teams. This is precisely why in many instances the availability of inpatient dermatology consultation is so important because nondermatologists often are unable to determine whether a rash is life-threatening, benign, or something in between. From the perspective of dermatology hospitalists, there is room for improvement in the flowchart Dobkin et al¹ presented to guide inpatient dermatology consultation.

To have a productive relationship with our internal medicine, surgery, pediatrics, psychiatry, and other hospital-based colleagues, we must keep an open mind when a consultation is received. We feel that the flowchart proposed by Dobkin et al¹ presents too narrow a viewpoint on the utility of inpatient dermatology. It rests on assertions that other teams will be able to determine the appropriate dermatologic diagnosis without involving a dermatologist, which often is not the case.

We disagree with several recommendations in the flowchart, the first being the assertion that patients who are “hemodynamically unstable due to [a] nondermatologic problem (eg, intubated on pressors, febrile, and hypotensive)” are not appropriate for inpatient dermatology consultation.¹ Although dermatologists do not commonly encounter patients with critical illness in the outpatient clinic, dermatology consultation can be extremely helpful and even lifesaving in the inpatient setting. It is unrealistic to expect the primary teams to know whether cutaneous manifestations potentially could be related to the patient’s overall clinical picture. On the contrary, we would encourage the primary team in charge of a hemodynamically unstable patient to consult dermatology at the first sign of an unexplained rash. Take for example an acutely ill patient who develops retiform purpura. There are well-established dermatology guidelines for the workup of retiform purpura,⁴ including prompt biopsy and assessment of broad, potentially life-threatening differential diagnoses from calciphylaxis to angioinvasive fungal infection. In this scenario, the dermatology consultant may render the correct diagnosis and recommend immediate treatment that could be lifesaving.

Secondly, we do not agree with the recommendation that a patient in hospice care is not appropriate for inpatient dermatology consultation. Patients receiving hospice or palliative care have high rates of potentially symptomatic cutaneous diseases,⁵ including intertrigo and dermatitis—comprising stasis, seborrheic, and contact dermatitis.⁶ Although aggressive intervention for asymptomatic benign or malignant skin conditions may not be in line with their goals of care, an inpatient dermatology consultation can reduce symptoms and improve quality of life. This population also is one that is unlikely to be able to attend an outpatient dermatology clinic appointment and therefore are good candidates for inpatient consultation.

Lastly, we want to highlight the difference between a stable chronic dermatologic disease and an acute flare that may occur while a patient is hospitalized, regardless of whether it is the reason for admission. For example, a patient with psoriasis affecting limited body surface area who is hospitalized for a myocardial infarction is not appropriate for a dermatology consultation. However, if that same patient develops erythroderma while they are hospitalized for cardiac monitoring, it would certainly be appropriate for dermatology to be consulted. Additionally, there are times when a chronic skin disease is the reason for hospitalization; dermatology, although technically a consulting service, would be the primary decision-maker for the patient’s care in this situation. In these scenarios, it is important for the patient to be able to establish care for long-term outpatient management of their condition; however, it is prudent to involve dermatology while the patient is acutely hospitalized to guide their treatment plan until they are able to see a dermatologist after discharge.

In conclusion, we believe that hospital dermatology is a valuable tool that can be utilized in many different scenarios. Although there are certainly situations more appropriate for outpatient dermatology referral, we would caution against overly simplified algorithms that could discourage valuable inpatient dermatology consultations. It often is worth a conversation with your dermatology consultant (when available at an institution) to determine the best course of action for each patient. Additionally, we recognize the need for more formalized guidelines on when to pursue inpatient dermatology consultation. We are members of the Society of Dermatology Hospitalists and encourage readers to reference their website, which provides additional resources on inpatient dermatology (https://societydermatologyhospitalists.com/inpatient-dermatology-literature/).

We appreciate the letter in response to our commentary on the appropriateness of inpatient dermatology consultations. It is the continued refining and re-evaluation of concepts such as these that allow our field to grow and improve knowledge and patient care.

We sought to provide a nonpatronizing yet simple consultation flowchart that would help guide triage of patients in need or not in need of dermatologic evaluation by the inpatient teams. Understandably, the impressions of our flowchart have been variable based on different readers’ medical backgrounds and experiences. It is certainly possible that our flowchart lacked certain exceptions and oversimplified certain concepts, and we welcome further refining of this flowchart to better guide inpatient dermatology consultations.

We do, however, disagree that the primary team would not know whether a patient is intubated in the intensive care unit for a dermatology reason. If the patient is in such a status, it would be pertinent for the primary team to conduct a timely workup that could include consultations until a diagnosis is made. We were not implying that every dermatology consultation in the intensive care unit is unwarranted, especially if it can lead to a primary dermatologic diagnosis. We do believe that a thorough history could elicit an allergy or other chronic skin condition that could save resources and spending within a hospital. Likewise, psoriasis comes in many different presentations, and although we do not believe a consultation for chronic psoriatic plaques is appropriate in the hospital, it is absolutely appropriate for a patient who is erythrodermic from any cause.

Our flowchart was intended to be the first step to providing education on when consultations are appropriate, and further refinement will be necessary.

Hershel Dobkin, MD; Timothy Blackwell, BS; Robin Ashinoff, MD

Drs. Dobkin and Ashinoff are from Hackensack University Medical Center, New Jersey. Mr. Blackwell is from the Rowan University School of Osteopathic Medicine, Stratford, New Jersey.

The authors report no conflict of interest.

Correspondence: Hershel Dobkin, MD, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601 (hersheldobkinpublic@gmail.com).

To the Editor:

We read with interest the Cutis article by Dobkin et al¹ (Cutis. 2022;109:218-220) regarding guidelines for inpatient and emergency department dermatology consultations. We agree with the authors that dermatology training is lacking in other medical specialties, which makes it challenging for teams to assess the appropriateness of a dermatology consultation in the inpatient setting. Inpatient dermatology consultation can be utilized in a hospital system to aid in rapid and accurate diagnosis, avoid inappropriate therapies, and decrease length of stay² and readmission rates³ while providing education to the primary teams. This is precisely why in many instances the availability of inpatient dermatology consultation is so important because nondermatologists often are unable to determine whether a rash is life-threatening, benign, or something in between. From the perspective of dermatology hospitalists, there is room for improvement in the flowchart Dobkin et al¹ presented to guide inpatient dermatology consultation.

To have a productive relationship with our internal medicine, surgery, pediatrics, psychiatry, and other hospital-based colleagues, we must keep an open mind when a consultation is received. We feel that the flowchart proposed by Dobkin et al¹ presents too narrow a viewpoint on the utility of inpatient dermatology. It rests on assertions that other teams will be able to determine the appropriate dermatologic diagnosis without involving a dermatologist, which often is not the case.

We disagree with several recommendations in the flowchart, the first being the assertion that patients who are “hemodynamically unstable due to [a] nondermatologic problem (eg, intubated on pressors, febrile, and hypotensive)” are not appropriate for inpatient dermatology consultation.¹ Although dermatologists do not commonly encounter patients with critical illness in the outpatient clinic, dermatology consultation can be extremely helpful and even lifesaving in the inpatient setting. It is unrealistic to expect the primary teams to know whether cutaneous manifestations potentially could be related to the patient’s overall clinical picture. On the contrary, we would encourage the primary team in charge of a hemodynamically unstable patient to consult dermatology at the first sign of an unexplained rash. Take for example an acutely ill patient who develops retiform purpura. There are well-established dermatology guidelines for the workup of retiform purpura,⁴ including prompt biopsy and assessment of broad, potentially life-threatening differential diagnoses from calciphylaxis to angioinvasive fungal infection. In this scenario, the dermatology consultant may render the correct diagnosis and recommend immediate treatment that could be lifesaving.

Secondly, we do not agree with the recommendation that a patient in hospice care is not appropriate for inpatient dermatology consultation. Patients receiving hospice or palliative care have high rates of potentially symptomatic cutaneous diseases,⁵ including intertrigo and dermatitis—comprising stasis, seborrheic, and contact dermatitis.⁶ Although aggressive intervention for asymptomatic benign or malignant skin conditions may not be in line with their goals of care, an inpatient dermatology consultation can reduce symptoms and improve quality of life. This population also is one that is unlikely to be able to attend an outpatient dermatology clinic appointment and therefore are good candidates for inpatient consultation.

Lastly, we want to highlight the difference between a stable chronic dermatologic disease and an acute flare that may occur while a patient is hospitalized, regardless of whether it is the reason for admission. For example, a patient with psoriasis affecting limited body surface area who is hospitalized for a myocardial infarction is not appropriate for a dermatology consultation. However, if that same patient develops erythroderma while they are hospitalized for cardiac monitoring, it would certainly be appropriate for dermatology to be consulted. Additionally, there are times when a chronic skin disease is the reason for hospitalization; dermatology, although technically a consulting service, would be the primary decision-maker for the patient’s care in this situation. In these scenarios, it is important for the patient to be able to establish care for long-term outpatient management of their condition; however, it is prudent to involve dermatology while the patient is acutely hospitalized to guide their treatment plan until they are able to see a dermatologist after discharge.

In conclusion, we believe that hospital dermatology is a valuable tool that can be utilized in many different scenarios. Although there are certainly situations more appropriate for outpatient dermatology referral, we would caution against overly simplified algorithms that could discourage valuable inpatient dermatology consultations. It often is worth a conversation with your dermatology consultant (when available at an institution) to determine the best course of action for each patient. Additionally, we recognize the need for more formalized guidelines on when to pursue inpatient dermatology consultation. We are members of the Society of Dermatology Hospitalists and encourage readers to reference their website, which provides additional resources on inpatient dermatology (https://societydermatologyhospitalists.com/inpatient-dermatology-literature/).

We appreciate the letter in response to our commentary on the appropriateness of inpatient dermatology consultations. It is the continued refining and re-evaluation of concepts such as these that allow our field to grow and improve knowledge and patient care.

We sought to provide a nonpatronizing yet simple consultation flowchart that would help guide triage of patients in need or not in need of dermatologic evaluation by the inpatient teams. Understandably, the impressions of our flowchart have been variable based on different readers’ medical backgrounds and experiences. It is certainly possible that our flowchart lacked certain exceptions and oversimplified certain concepts, and we welcome further refining of this flowchart to better guide inpatient dermatology consultations.

We do, however, disagree that the primary team would not know whether a patient is intubated in the intensive care unit for a dermatology reason. If the patient is in such a status, it would be pertinent for the primary team to conduct a timely workup that could include consultations until a diagnosis is made. We were not implying that every dermatology consultation in the intensive care unit is unwarranted, especially if it can lead to a primary dermatologic diagnosis. We do believe that a thorough history could elicit an allergy or other chronic skin condition that could save resources and spending within a hospital. Likewise, psoriasis comes in many different presentations, and although we do not believe a consultation for chronic psoriatic plaques is appropriate in the hospital, it is absolutely appropriate for a patient who is erythrodermic from any cause.

Our flowchart was intended to be the first step to providing education on when consultations are appropriate, and further refinement will be necessary.

Hershel Dobkin, MD; Timothy Blackwell, BS; Robin Ashinoff, MD

Drs. Dobkin and Ashinoff are from Hackensack University Medical Center, New Jersey. Mr. Blackwell is from the Rowan University School of Osteopathic Medicine, Stratford, New Jersey.

The authors report no conflict of interest.

Correspondence: Hershel Dobkin, MD, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601 (hersheldobkinpublic@gmail.com).

To the Editor:

We read with interest the Cutis article by Dobkin et al¹ (Cutis. 2022;109:218-220) regarding guidelines for inpatient and emergency department dermatology consultations. We agree with the authors that dermatology training is lacking in other medical specialties, which makes it challenging for teams to assess the appropriateness of a dermatology consultation in the inpatient setting. Inpatient dermatology consultation can be utilized in a hospital system to aid in rapid and accurate diagnosis, avoid inappropriate therapies, and decrease length of stay² and readmission rates³ while providing education to the primary teams. This is precisely why in many instances the availability of inpatient dermatology consultation is so important because nondermatologists often are unable to determine whether a rash is life-threatening, benign, or something in between. From the perspective of dermatology hospitalists, there is room for improvement in the flowchart Dobkin et al¹ presented to guide inpatient dermatology consultation.

To have a productive relationship with our internal medicine, surgery, pediatrics, psychiatry, and other hospital-based colleagues, we must keep an open mind when a consultation is received. We feel that the flowchart proposed by Dobkin et al¹ presents too narrow a viewpoint on the utility of inpatient dermatology. It rests on assertions that other teams will be able to determine the appropriate dermatologic diagnosis without involving a dermatologist, which often is not the case.

We disagree with several recommendations in the flowchart, the first being the assertion that patients who are “hemodynamically unstable due to [a] nondermatologic problem (eg, intubated on pressors, febrile, and hypotensive)” are not appropriate for inpatient dermatology consultation.¹ Although dermatologists do not commonly encounter patients with critical illness in the outpatient clinic, dermatology consultation can be extremely helpful and even lifesaving in the inpatient setting. It is unrealistic to expect the primary teams to know whether cutaneous manifestations potentially could be related to the patient’s overall clinical picture. On the contrary, we would encourage the primary team in charge of a hemodynamically unstable patient to consult dermatology at the first sign of an unexplained rash. Take for example an acutely ill patient who develops retiform purpura. There are well-established dermatology guidelines for the workup of retiform purpura,⁴ including prompt biopsy and assessment of broad, potentially life-threatening differential diagnoses from calciphylaxis to angioinvasive fungal infection. In this scenario, the dermatology consultant may render the correct diagnosis and recommend immediate treatment that could be lifesaving.

Secondly, we do not agree with the recommendation that a patient in hospice care is not appropriate for inpatient dermatology consultation. Patients receiving hospice or palliative care have high rates of potentially symptomatic cutaneous diseases,⁵ including intertrigo and dermatitis—comprising stasis, seborrheic, and contact dermatitis.⁶ Although aggressive intervention for asymptomatic benign or malignant skin conditions may not be in line with their goals of care, an inpatient dermatology consultation can reduce symptoms and improve quality of life. This population also is one that is unlikely to be able to attend an outpatient dermatology clinic appointment and therefore are good candidates for inpatient consultation.

Lastly, we want to highlight the difference between a stable chronic dermatologic disease and an acute flare that may occur while a patient is hospitalized, regardless of whether it is the reason for admission. For example, a patient with psoriasis affecting limited body surface area who is hospitalized for a myocardial infarction is not appropriate for a dermatology consultation. However, if that same patient develops erythroderma while they are hospitalized for cardiac monitoring, it would certainly be appropriate for dermatology to be consulted. Additionally, there are times when a chronic skin disease is the reason for hospitalization; dermatology, although technically a consulting service, would be the primary decision-maker for the patient’s care in this situation. In these scenarios, it is important for the patient to be able to establish care for long-term outpatient management of their condition; however, it is prudent to involve dermatology while the patient is acutely hospitalized to guide their treatment plan until they are able to see a dermatologist after discharge.

In conclusion, we believe that hospital dermatology is a valuable tool that can be utilized in many different scenarios. Although there are certainly situations more appropriate for outpatient dermatology referral, we would caution against overly simplified algorithms that could discourage valuable inpatient dermatology consultations. It often is worth a conversation with your dermatology consultant (when available at an institution) to determine the best course of action for each patient. Additionally, we recognize the need for more formalized guidelines on when to pursue inpatient dermatology consultation. We are members of the Society of Dermatology Hospitalists and encourage readers to reference their website, which provides additional resources on inpatient dermatology (https://societydermatologyhospitalists.com/inpatient-dermatology-literature/).

We appreciate the letter in response to our commentary on the appropriateness of inpatient dermatology consultations. It is the continued refining and re-evaluation of concepts such as these that allow our field to grow and improve knowledge and patient care.

We sought to provide a nonpatronizing yet simple consultation flowchart that would help guide triage of patients in need or not in need of dermatologic evaluation by the inpatient teams. Understandably, the impressions of our flowchart have been variable based on different readers’ medical backgrounds and experiences. It is certainly possible that our flowchart lacked certain exceptions and oversimplified certain concepts, and we welcome further refining of this flowchart to better guide inpatient dermatology consultations.

We do, however, disagree that the primary team would not know whether a patient is intubated in the intensive care unit for a dermatology reason. If the patient is in such a status, it would be pertinent for the primary team to conduct a timely workup that could include consultations until a diagnosis is made. We were not implying that every dermatology consultation in the intensive care unit is unwarranted, especially if it can lead to a primary dermatologic diagnosis. We do believe that a thorough history could elicit an allergy or other chronic skin condition that could save resources and spending within a hospital. Likewise, psoriasis comes in many different presentations, and although we do not believe a consultation for chronic psoriatic plaques is appropriate in the hospital, it is absolutely appropriate for a patient who is erythrodermic from any cause.

Our flowchart was intended to be the first step to providing education on when consultations are appropriate, and further refinement will be necessary.

Hershel Dobkin, MD; Timothy Blackwell, BS; Robin Ashinoff, MD

Drs. Dobkin and Ashinoff are from Hackensack University Medical Center, New Jersey. Mr. Blackwell is from the Rowan University School of Osteopathic Medicine, Stratford, New Jersey.

The authors report no conflict of interest.

Correspondence: Hershel Dobkin, MD, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601 (hersheldobkinpublic@gmail.com).

Dermatology is one of the least diverse medical specialties with only 3% of dermatologists being Black and 4% Latinx.¹ Leading dermatology organizations have called for specialty-wide efforts to improve diversity, with a particular focus on the resident selection process.^2,3 Medical students who are underrepresented in medicine (UIM)(ie, those who identify as Black, Latinx, Native American, or Pacific Islander) face many potential barriers in applying to dermatology programs, including financial limitations, lack of support and mentorship, and less exposure to the specialty.^1,2,4 The COVID-19 pandemic introduced additional challenges in the residency application process with limitations on clinical, research, and volunteer experiences; decreased opportunities for in-person mentorship and away rotations; and a shift to virtual recruitment. Although there has been increased emphasis on recruiting diverse candidates to dermatology, the COVID-19 pandemic may have exacerbated existing barriers for UIM applicants.

We surveyed dermatology residency program directors (PDs) and applicants to evaluate how UIM students approach and fare in the dermatology residency application process as well as the effects of COVID-19 on the most recent application cycle. Herein, we report the results of our surveys with a focus on racial differences in the application process.

Methods

We administered 2 anonymous online surveys—one to 115 PDs through the Association of Professors of Dermatology (APD) email listserve and another to applicants who participated in the 2020-2021 dermatology residency application cycle through the Dermatology Interest Group Association (DIGA) listserve. The surveys were distributed from March 29 through May 23, 2021. There was no way to determine the number of dermatology applicants on the DIGA listserve. The surveys were reviewed and approved by the University of Southern California (Los Angeles, California) institutional review board (approval #UP-21-00118).

Participants were not required to answer every survey question; response rates varied by question. Survey responses with less than 10% completion were excluded from analysis. Data were collected, analyzed, and stored using Qualtrics, a secure online survey platform. The test of equal or given proportions in R studio was used to determine statistically significant differences between variables (P<.05 indicated statistical significance).

Results

The PD survey received 79 complete responses (83.5% complete responses, 73.8% response rate) and the applicant survey received 232 complete responses (83.6% complete responses).

Applicant Characteristics—Applicant characteristics are provided in the eTable; 13.2% and 8.4% of participants were Black and Latinx (including those who identify as Hispanic/Latino), respectively. Only 0.8% of respondents identified as American Indian or Alaskan Native and were excluded from the analysis due to the limited sample size. Those who identified as White, Asian, multiple races, or other and those who preferred not to answer were considered non-UIM participants.

Differences in family background were observed in our cohort, with UIM candidates more likely to have experienced disadvantages, defined as being the first in their family to attend college/graduate school, growing up in a rural area, being a first-generation immigrant, or qualifying as low income. Underrepresented in medicine applicants also were less likely to have a dermatology program at their medical school (both Black and Latinx) and to have been elected to honor societies such as Alpha Omega Alpha and the Gold Humanism Honor Society (Black only).

Underrepresented in medicine applicants were more likely to complete a research gap year (eTable). Most applicants who took research years did so to improve their chances of matching, regardless of their race/ethnicity. For those who did not complete a research year, Black applicants (46.7%) were more likely to base that decision on financial limitations compared to non-UIMs (18.6%, P<.0001). Interestingly, in the PD survey, only 4.5% of respondents considered completion of a research year extremely or very important when compiling rank lists.

Application Process and Match Outcomes—The Table highlights differences in how UIM applicants approached the application process. Black but not Latinx applicants were less likely to be first-time applicants to dermatology compared to non-UIM applicants. Black applicants (8.3%) were significantly less likely to apply to more than 100 programs compared to non-UIM applicants (29.5%, P=.0002). Underrepresented in medicine applicants received greater numbers of interviews despite applying to fewer programs overall.

There also were differences in how UIM candidates approached their rank lists, with Black and Latinx applicants prioritizing diversity of patient populations and program faculty as well as program missions and values (Figure).

In our cohort, UIM candidates were more likely than non-UIM to match, and Black applicants were most likely to match at one of their top 3 choices (Table). In the PD survey, 77.6% of PDs considered contribution to diversity an important factor when compiling their rank lists.

Comment

Applicant Background—Dermatology is a competitive specialty with a challenging application process² that has been further complicated by the COVID-19 pandemic. Our study elucidated how the 2020-2021 application cycle affected UIM dermatology applicants. Prior studies have found that UIM medical students were more likely to come from lower socioeconomic backgrounds; financial constraints pose a major barrier for UIM and low-income students interested in dermatology.^4-6 We found this to be true in our cohort, as Black and Latinx applicants were significantly more likely to come from disadvantaged backgrounds (P<.000008 and P=.006, respectively). Additionally, we found that Black applicants were more likely than any other group to indicate financial concerns as their primary reason for not taking a research gap year. 

Although most applicants who completed a research year did so to increase their chances of matching, a higher percentage of UIMs took research years compared to non-UIM applicants. This finding could indicate greater anxiety about matching among UIM applicants vs their non-UIM counterparts. Black students have faced discrimination in clinical grading,⁷ have perceived racial discrimination in residency interviews,^8,9 and have shown to be less likely to be elected to medical school honor societies.¹⁰ We found that UIM applicants were more likely to pursue a research year compared to other applicants,¹¹ possibly because they felt additional pressure to enhance their applications or because UIM candidates were less likely to have a home dermatology program. Expansion of mentorship programs, visiting student electives, and grants for UIMs may alleviate the need for these candidates to complete a research year and reduce disparities in the application process.

Factors Influencing Rank Lists for Applicants—In our cohort, UIMs were significantly more likely to rank diversity of patients (P<.0001 for Black applicants and P=.04 for Latinx applicants) and faculty (P<.001 for Black applicants and P<.001 for Latinx applicants) as important factors in choosing a residency program. Historically, dermatology has been disproportionately White in its physician workforce and patient population.^1,12 Students with lower incomes or who identify as minorities cite the lack of diversity in dermatology as a considerable barrier to pursuing a career in the specialty.^4,5 Service learning, pipeline programs aimed at early exposure to dermatology, and increased access to care for diverse patient populations are important measures to improve diversity in the dermatology workforce.^13-15 Residency programs should consider how to incorporate these aspects into didactic and clinical curricula to better recruit diverse candidates to the field.

Equity in the Application Process—We found that Black applicants were more likely than non-UIM applicants to be reapplicants to dermatology; however, Black applicants in our study also were more likely to receive more interview invites, match into dermatology, and match into one of their top 3 programs. These findings are interesting, particularly given concerns about equity in the application process. It is possible that Black applicants who overcome barriers to applying to dermatology ultimately are more successful applicants. Recently, there has been an increased focus in the field on diversifying dermatology, which was further intensified last year.^2,3 Indicative of this shift, our PD survey showed that most programs reported that applicants’ contributions to diversity were important factors in the application process. Additionally, an emphasis by PDs on a holistic review of applications coupled with direct advocacy for increased representation may have contributed to the increased match rates for UIM applicants reported in our survey.

Latinx Applicants—Our study showed differences in how Latinx candidates fared in the application process; although Latinx applicants were more likely than their non-Latinx counterparts to match into dermatology, they were less likely than non-Latinx applicants to match into one of their top 3 programs. Given that Latinx encompasses ethnicity, not race, there may be a difference in how intentional focus on and advocacy for increasing diversity in dermatology affected different UIM applicant groups. Both race and ethnicity are social constructs rather than scientific categorizations; thus, it is difficult in survey studies such as ours to capture the intersectionality present across and between groups. Lastly, it is possible that the respondents to our applicant survey are not representative of the full cohort of UIM applicants.

Study Limitations—A major limitation of our study was that we did not have a method of reaching all dermatology applicants. Although our study shows promising results suggestive of increased diversity in the last application cycle, release of the National Resident Matching Program results from 2020-2021 with racially stratified data will be imperative to assess equity in the match process for all specialties and to confirm the generalizability of our results.

Dermatology is one of the least diverse medical specialties with only 3% of dermatologists being Black and 4% Latinx.¹ Leading dermatology organizations have called for specialty-wide efforts to improve diversity, with a particular focus on the resident selection process.^2,3 Medical students who are underrepresented in medicine (UIM)(ie, those who identify as Black, Latinx, Native American, or Pacific Islander) face many potential barriers in applying to dermatology programs, including financial limitations, lack of support and mentorship, and less exposure to the specialty.^1,2,4 The COVID-19 pandemic introduced additional challenges in the residency application process with limitations on clinical, research, and volunteer experiences; decreased opportunities for in-person mentorship and away rotations; and a shift to virtual recruitment. Although there has been increased emphasis on recruiting diverse candidates to dermatology, the COVID-19 pandemic may have exacerbated existing barriers for UIM applicants.

We surveyed dermatology residency program directors (PDs) and applicants to evaluate how UIM students approach and fare in the dermatology residency application process as well as the effects of COVID-19 on the most recent application cycle. Herein, we report the results of our surveys with a focus on racial differences in the application process.

Methods

We administered 2 anonymous online surveys—one to 115 PDs through the Association of Professors of Dermatology (APD) email listserve and another to applicants who participated in the 2020-2021 dermatology residency application cycle through the Dermatology Interest Group Association (DIGA) listserve. The surveys were distributed from March 29 through May 23, 2021. There was no way to determine the number of dermatology applicants on the DIGA listserve. The surveys were reviewed and approved by the University of Southern California (Los Angeles, California) institutional review board (approval #UP-21-00118).

Participants were not required to answer every survey question; response rates varied by question. Survey responses with less than 10% completion were excluded from analysis. Data were collected, analyzed, and stored using Qualtrics, a secure online survey platform. The test of equal or given proportions in R studio was used to determine statistically significant differences between variables (P<.05 indicated statistical significance).

Results

The PD survey received 79 complete responses (83.5% complete responses, 73.8% response rate) and the applicant survey received 232 complete responses (83.6% complete responses).

Applicant Characteristics—Applicant characteristics are provided in the eTable; 13.2% and 8.4% of participants were Black and Latinx (including those who identify as Hispanic/Latino), respectively. Only 0.8% of respondents identified as American Indian or Alaskan Native and were excluded from the analysis due to the limited sample size. Those who identified as White, Asian, multiple races, or other and those who preferred not to answer were considered non-UIM participants.

Differences in family background were observed in our cohort, with UIM candidates more likely to have experienced disadvantages, defined as being the first in their family to attend college/graduate school, growing up in a rural area, being a first-generation immigrant, or qualifying as low income. Underrepresented in medicine applicants also were less likely to have a dermatology program at their medical school (both Black and Latinx) and to have been elected to honor societies such as Alpha Omega Alpha and the Gold Humanism Honor Society (Black only).

Underrepresented in medicine applicants were more likely to complete a research gap year (eTable). Most applicants who took research years did so to improve their chances of matching, regardless of their race/ethnicity. For those who did not complete a research year, Black applicants (46.7%) were more likely to base that decision on financial limitations compared to non-UIMs (18.6%, P<.0001). Interestingly, in the PD survey, only 4.5% of respondents considered completion of a research year extremely or very important when compiling rank lists.

Application Process and Match Outcomes—The Table highlights differences in how UIM applicants approached the application process. Black but not Latinx applicants were less likely to be first-time applicants to dermatology compared to non-UIM applicants. Black applicants (8.3%) were significantly less likely to apply to more than 100 programs compared to non-UIM applicants (29.5%, P=.0002). Underrepresented in medicine applicants received greater numbers of interviews despite applying to fewer programs overall.

There also were differences in how UIM candidates approached their rank lists, with Black and Latinx applicants prioritizing diversity of patient populations and program faculty as well as program missions and values (Figure).

In our cohort, UIM candidates were more likely than non-UIM to match, and Black applicants were most likely to match at one of their top 3 choices (Table). In the PD survey, 77.6% of PDs considered contribution to diversity an important factor when compiling their rank lists.

Comment

Applicant Background—Dermatology is a competitive specialty with a challenging application process² that has been further complicated by the COVID-19 pandemic. Our study elucidated how the 2020-2021 application cycle affected UIM dermatology applicants. Prior studies have found that UIM medical students were more likely to come from lower socioeconomic backgrounds; financial constraints pose a major barrier for UIM and low-income students interested in dermatology.^4-6 We found this to be true in our cohort, as Black and Latinx applicants were significantly more likely to come from disadvantaged backgrounds (P<.000008 and P=.006, respectively). Additionally, we found that Black applicants were more likely than any other group to indicate financial concerns as their primary reason for not taking a research gap year. 

Although most applicants who completed a research year did so to increase their chances of matching, a higher percentage of UIMs took research years compared to non-UIM applicants. This finding could indicate greater anxiety about matching among UIM applicants vs their non-UIM counterparts. Black students have faced discrimination in clinical grading,⁷ have perceived racial discrimination in residency interviews,^8,9 and have shown to be less likely to be elected to medical school honor societies.¹⁰ We found that UIM applicants were more likely to pursue a research year compared to other applicants,¹¹ possibly because they felt additional pressure to enhance their applications or because UIM candidates were less likely to have a home dermatology program. Expansion of mentorship programs, visiting student electives, and grants for UIMs may alleviate the need for these candidates to complete a research year and reduce disparities in the application process.

Factors Influencing Rank Lists for Applicants—In our cohort, UIMs were significantly more likely to rank diversity of patients (P<.0001 for Black applicants and P=.04 for Latinx applicants) and faculty (P<.001 for Black applicants and P<.001 for Latinx applicants) as important factors in choosing a residency program. Historically, dermatology has been disproportionately White in its physician workforce and patient population.^1,12 Students with lower incomes or who identify as minorities cite the lack of diversity in dermatology as a considerable barrier to pursuing a career in the specialty.^4,5 Service learning, pipeline programs aimed at early exposure to dermatology, and increased access to care for diverse patient populations are important measures to improve diversity in the dermatology workforce.^13-15 Residency programs should consider how to incorporate these aspects into didactic and clinical curricula to better recruit diverse candidates to the field.

Equity in the Application Process—We found that Black applicants were more likely than non-UIM applicants to be reapplicants to dermatology; however, Black applicants in our study also were more likely to receive more interview invites, match into dermatology, and match into one of their top 3 programs. These findings are interesting, particularly given concerns about equity in the application process. It is possible that Black applicants who overcome barriers to applying to dermatology ultimately are more successful applicants. Recently, there has been an increased focus in the field on diversifying dermatology, which was further intensified last year.^2,3 Indicative of this shift, our PD survey showed that most programs reported that applicants’ contributions to diversity were important factors in the application process. Additionally, an emphasis by PDs on a holistic review of applications coupled with direct advocacy for increased representation may have contributed to the increased match rates for UIM applicants reported in our survey.

Latinx Applicants—Our study showed differences in how Latinx candidates fared in the application process; although Latinx applicants were more likely than their non-Latinx counterparts to match into dermatology, they were less likely than non-Latinx applicants to match into one of their top 3 programs. Given that Latinx encompasses ethnicity, not race, there may be a difference in how intentional focus on and advocacy for increasing diversity in dermatology affected different UIM applicant groups. Both race and ethnicity are social constructs rather than scientific categorizations; thus, it is difficult in survey studies such as ours to capture the intersectionality present across and between groups. Lastly, it is possible that the respondents to our applicant survey are not representative of the full cohort of UIM applicants.

Study Limitations—A major limitation of our study was that we did not have a method of reaching all dermatology applicants. Although our study shows promising results suggestive of increased diversity in the last application cycle, release of the National Resident Matching Program results from 2020-2021 with racially stratified data will be imperative to assess equity in the match process for all specialties and to confirm the generalizability of our results.

Dermatology is one of the least diverse medical specialties with only 3% of dermatologists being Black and 4% Latinx.¹ Leading dermatology organizations have called for specialty-wide efforts to improve diversity, with a particular focus on the resident selection process.^2,3 Medical students who are underrepresented in medicine (UIM)(ie, those who identify as Black, Latinx, Native American, or Pacific Islander) face many potential barriers in applying to dermatology programs, including financial limitations, lack of support and mentorship, and less exposure to the specialty.^1,2,4 The COVID-19 pandemic introduced additional challenges in the residency application process with limitations on clinical, research, and volunteer experiences; decreased opportunities for in-person mentorship and away rotations; and a shift to virtual recruitment. Although there has been increased emphasis on recruiting diverse candidates to dermatology, the COVID-19 pandemic may have exacerbated existing barriers for UIM applicants.

We surveyed dermatology residency program directors (PDs) and applicants to evaluate how UIM students approach and fare in the dermatology residency application process as well as the effects of COVID-19 on the most recent application cycle. Herein, we report the results of our surveys with a focus on racial differences in the application process.

Methods

We administered 2 anonymous online surveys—one to 115 PDs through the Association of Professors of Dermatology (APD) email listserve and another to applicants who participated in the 2020-2021 dermatology residency application cycle through the Dermatology Interest Group Association (DIGA) listserve. The surveys were distributed from March 29 through May 23, 2021. There was no way to determine the number of dermatology applicants on the DIGA listserve. The surveys were reviewed and approved by the University of Southern California (Los Angeles, California) institutional review board (approval #UP-21-00118).

Participants were not required to answer every survey question; response rates varied by question. Survey responses with less than 10% completion were excluded from analysis. Data were collected, analyzed, and stored using Qualtrics, a secure online survey platform. The test of equal or given proportions in R studio was used to determine statistically significant differences between variables (P<.05 indicated statistical significance).

Results

The PD survey received 79 complete responses (83.5% complete responses, 73.8% response rate) and the applicant survey received 232 complete responses (83.6% complete responses).

Applicant Characteristics—Applicant characteristics are provided in the eTable; 13.2% and 8.4% of participants were Black and Latinx (including those who identify as Hispanic/Latino), respectively. Only 0.8% of respondents identified as American Indian or Alaskan Native and were excluded from the analysis due to the limited sample size. Those who identified as White, Asian, multiple races, or other and those who preferred not to answer were considered non-UIM participants.

Differences in family background were observed in our cohort, with UIM candidates more likely to have experienced disadvantages, defined as being the first in their family to attend college/graduate school, growing up in a rural area, being a first-generation immigrant, or qualifying as low income. Underrepresented in medicine applicants also were less likely to have a dermatology program at their medical school (both Black and Latinx) and to have been elected to honor societies such as Alpha Omega Alpha and the Gold Humanism Honor Society (Black only).

Underrepresented in medicine applicants were more likely to complete a research gap year (eTable). Most applicants who took research years did so to improve their chances of matching, regardless of their race/ethnicity. For those who did not complete a research year, Black applicants (46.7%) were more likely to base that decision on financial limitations compared to non-UIMs (18.6%, P<.0001). Interestingly, in the PD survey, only 4.5% of respondents considered completion of a research year extremely or very important when compiling rank lists.

Application Process and Match Outcomes—The Table highlights differences in how UIM applicants approached the application process. Black but not Latinx applicants were less likely to be first-time applicants to dermatology compared to non-UIM applicants. Black applicants (8.3%) were significantly less likely to apply to more than 100 programs compared to non-UIM applicants (29.5%, P=.0002). Underrepresented in medicine applicants received greater numbers of interviews despite applying to fewer programs overall.

There also were differences in how UIM candidates approached their rank lists, with Black and Latinx applicants prioritizing diversity of patient populations and program faculty as well as program missions and values (Figure).

In our cohort, UIM candidates were more likely than non-UIM to match, and Black applicants were most likely to match at one of their top 3 choices (Table). In the PD survey, 77.6% of PDs considered contribution to diversity an important factor when compiling their rank lists.

Comment

Applicant Background—Dermatology is a competitive specialty with a challenging application process² that has been further complicated by the COVID-19 pandemic. Our study elucidated how the 2020-2021 application cycle affected UIM dermatology applicants. Prior studies have found that UIM medical students were more likely to come from lower socioeconomic backgrounds; financial constraints pose a major barrier for UIM and low-income students interested in dermatology.^4-6 We found this to be true in our cohort, as Black and Latinx applicants were significantly more likely to come from disadvantaged backgrounds (P<.000008 and P=.006, respectively). Additionally, we found that Black applicants were more likely than any other group to indicate financial concerns as their primary reason for not taking a research gap year. 

Although most applicants who completed a research year did so to increase their chances of matching, a higher percentage of UIMs took research years compared to non-UIM applicants. This finding could indicate greater anxiety about matching among UIM applicants vs their non-UIM counterparts. Black students have faced discrimination in clinical grading,⁷ have perceived racial discrimination in residency interviews,^8,9 and have shown to be less likely to be elected to medical school honor societies.¹⁰ We found that UIM applicants were more likely to pursue a research year compared to other applicants,¹¹ possibly because they felt additional pressure to enhance their applications or because UIM candidates were less likely to have a home dermatology program. Expansion of mentorship programs, visiting student electives, and grants for UIMs may alleviate the need for these candidates to complete a research year and reduce disparities in the application process.

Factors Influencing Rank Lists for Applicants—In our cohort, UIMs were significantly more likely to rank diversity of patients (P<.0001 for Black applicants and P=.04 for Latinx applicants) and faculty (P<.001 for Black applicants and P<.001 for Latinx applicants) as important factors in choosing a residency program. Historically, dermatology has been disproportionately White in its physician workforce and patient population.^1,12 Students with lower incomes or who identify as minorities cite the lack of diversity in dermatology as a considerable barrier to pursuing a career in the specialty.^4,5 Service learning, pipeline programs aimed at early exposure to dermatology, and increased access to care for diverse patient populations are important measures to improve diversity in the dermatology workforce.^13-15 Residency programs should consider how to incorporate these aspects into didactic and clinical curricula to better recruit diverse candidates to the field.

Equity in the Application Process—We found that Black applicants were more likely than non-UIM applicants to be reapplicants to dermatology; however, Black applicants in our study also were more likely to receive more interview invites, match into dermatology, and match into one of their top 3 programs. These findings are interesting, particularly given concerns about equity in the application process. It is possible that Black applicants who overcome barriers to applying to dermatology ultimately are more successful applicants. Recently, there has been an increased focus in the field on diversifying dermatology, which was further intensified last year.^2,3 Indicative of this shift, our PD survey showed that most programs reported that applicants’ contributions to diversity were important factors in the application process. Additionally, an emphasis by PDs on a holistic review of applications coupled with direct advocacy for increased representation may have contributed to the increased match rates for UIM applicants reported in our survey.

Latinx Applicants—Our study showed differences in how Latinx candidates fared in the application process; although Latinx applicants were more likely than their non-Latinx counterparts to match into dermatology, they were less likely than non-Latinx applicants to match into one of their top 3 programs. Given that Latinx encompasses ethnicity, not race, there may be a difference in how intentional focus on and advocacy for increasing diversity in dermatology affected different UIM applicant groups. Both race and ethnicity are social constructs rather than scientific categorizations; thus, it is difficult in survey studies such as ours to capture the intersectionality present across and between groups. Lastly, it is possible that the respondents to our applicant survey are not representative of the full cohort of UIM applicants.

Study Limitations—A major limitation of our study was that we did not have a method of reaching all dermatology applicants. Although our study shows promising results suggestive of increased diversity in the last application cycle, release of the National Resident Matching Program results from 2020-2021 with racially stratified data will be imperative to assess equity in the match process for all specialties and to confirm the generalizability of our results.

We are excited to announce a new partnership between Cutis and the Association of Professors of Dermatology Residency Program Directors Section (APD-RPDS). The new APD-RPDS column Residency Roundup will contain quarterly communications and submissions that we hope will facilitate greater dissemination of information that is useful to the dermatology teaching community.

The APD is a group of academic dermatologists whose membership comprises chairs, chiefs, residency and fellowship program directors, and teaching faculty. Each fall, the group convenes in Chicago, Illinois, for a 2-day meeting centered around departmental and program leadership with a focus on education. The APD-RPDS was formed in 2020 and is led by a steering committee of 9 members, including our current Chair, Ilana S. Rosman, MD (Washington University School of Medicine, St. Louis, Missouri), and Vice Chair, Jo-Ann M. Latkowski, MD (New York University, New York). Committee members are elected from and by the APD membership and must serve in program leadership at their home programs. The APD-RPDS helps plan and coordinate breakout sessions and lectures at the annual APD meeting, which typically relate to program director duties, changing policies within the American Board of Dermatology or Accreditation Council for Graduate Medical Education, ideas for future growth, and changes in our specialty and in resident education. Members of the APD-RPDS have access to the APD listserv, a valuable resource for discussing issues affecting residency training. We also have work groups led by our members, which include diversity, equity, and inclusion; resource development; communications; and the annual survey. To join the APD, the RPDS, and/or any of our workgroups, please reach out to us or visit the APD website (https://www.dermatologyprofessors.org).

We look forward to welcoming and expediently reviewing members’ submissions to the new Residency Roundup column falling into 2 principal categories within the scope of dermatologic recruitment, didactic education, and clinical training. The first category will feature novel tools, programs, and platforms to improve dermatology training through collaboration. This could entail a description of a new platform designed for sharing resources among programs and specialties to enhance learning for trainees and faculty alike. For example, if a database is created that contains prerecorded lectures pertaining to alopecia, a potential article submission might introduce the database and provide information on what topics are covered and how to access these lectures for readers worldwide. Likewise, if a new technology emerges that allows for easier collaboration among programs, a possible submission would introduce the technology and discuss its potential benefits to trainees, faculty, and practicing dermatologists.

Secondly and more commonly, we anticipate the Residency Roundup column will feature articles that delve into the critical issues and challenges currently impacting recruitment, training, and administration in dermatology residency programs. Specific topics may include but are not limited to recruitment of underrepresented in medicine applicants to dermatology, technological advances to improve teaching methods within training programs, surveys delving into the dermatology match process, and educational gaps or future directions in the specialty. The column occasionally may be used to disseminate information from our section of the APD, including consensus statements or editorials related to changes implemented in the dermatology residency application process. A prospective editorial on this subject could explore varying viewpoints of implemented and proposed changes as well as the reasons behind the changes.

Our group is collaborative, and our aim is to improve education, equity, management of program director responsibilities, and the dermatology application process for programs and applicants alike. With your input, experience, and varied perspectives, we look forward to moving the field of dermatology to a better future by working together. 

We are excited to announce a new partnership between Cutis and the Association of Professors of Dermatology Residency Program Directors Section (APD-RPDS). The new APD-RPDS column Residency Roundup will contain quarterly communications and submissions that we hope will facilitate greater dissemination of information that is useful to the dermatology teaching community.

The APD is a group of academic dermatologists whose membership comprises chairs, chiefs, residency and fellowship program directors, and teaching faculty. Each fall, the group convenes in Chicago, Illinois, for a 2-day meeting centered around departmental and program leadership with a focus on education. The APD-RPDS was formed in 2020 and is led by a steering committee of 9 members, including our current Chair, Ilana S. Rosman, MD (Washington University School of Medicine, St. Louis, Missouri), and Vice Chair, Jo-Ann M. Latkowski, MD (New York University, New York). Committee members are elected from and by the APD membership and must serve in program leadership at their home programs. The APD-RPDS helps plan and coordinate breakout sessions and lectures at the annual APD meeting, which typically relate to program director duties, changing policies within the American Board of Dermatology or Accreditation Council for Graduate Medical Education, ideas for future growth, and changes in our specialty and in resident education. Members of the APD-RPDS have access to the APD listserv, a valuable resource for discussing issues affecting residency training. We also have work groups led by our members, which include diversity, equity, and inclusion; resource development; communications; and the annual survey. To join the APD, the RPDS, and/or any of our workgroups, please reach out to us or visit the APD website (https://www.dermatologyprofessors.org).

We look forward to welcoming and expediently reviewing members’ submissions to the new Residency Roundup column falling into 2 principal categories within the scope of dermatologic recruitment, didactic education, and clinical training. The first category will feature novel tools, programs, and platforms to improve dermatology training through collaboration. This could entail a description of a new platform designed for sharing resources among programs and specialties to enhance learning for trainees and faculty alike. For example, if a database is created that contains prerecorded lectures pertaining to alopecia, a potential article submission might introduce the database and provide information on what topics are covered and how to access these lectures for readers worldwide. Likewise, if a new technology emerges that allows for easier collaboration among programs, a possible submission would introduce the technology and discuss its potential benefits to trainees, faculty, and practicing dermatologists.

Secondly and more commonly, we anticipate the Residency Roundup column will feature articles that delve into the critical issues and challenges currently impacting recruitment, training, and administration in dermatology residency programs. Specific topics may include but are not limited to recruitment of underrepresented in medicine applicants to dermatology, technological advances to improve teaching methods within training programs, surveys delving into the dermatology match process, and educational gaps or future directions in the specialty. The column occasionally may be used to disseminate information from our section of the APD, including consensus statements or editorials related to changes implemented in the dermatology residency application process. A prospective editorial on this subject could explore varying viewpoints of implemented and proposed changes as well as the reasons behind the changes.

Our group is collaborative, and our aim is to improve education, equity, management of program director responsibilities, and the dermatology application process for programs and applicants alike. With your input, experience, and varied perspectives, we look forward to moving the field of dermatology to a better future by working together. 

We are excited to announce a new partnership between Cutis and the Association of Professors of Dermatology Residency Program Directors Section (APD-RPDS). The new APD-RPDS column Residency Roundup will contain quarterly communications and submissions that we hope will facilitate greater dissemination of information that is useful to the dermatology teaching community.

The APD is a group of academic dermatologists whose membership comprises chairs, chiefs, residency and fellowship program directors, and teaching faculty. Each fall, the group convenes in Chicago, Illinois, for a 2-day meeting centered around departmental and program leadership with a focus on education. The APD-RPDS was formed in 2020 and is led by a steering committee of 9 members, including our current Chair, Ilana S. Rosman, MD (Washington University School of Medicine, St. Louis, Missouri), and Vice Chair, Jo-Ann M. Latkowski, MD (New York University, New York). Committee members are elected from and by the APD membership and must serve in program leadership at their home programs. The APD-RPDS helps plan and coordinate breakout sessions and lectures at the annual APD meeting, which typically relate to program director duties, changing policies within the American Board of Dermatology or Accreditation Council for Graduate Medical Education, ideas for future growth, and changes in our specialty and in resident education. Members of the APD-RPDS have access to the APD listserv, a valuable resource for discussing issues affecting residency training. We also have work groups led by our members, which include diversity, equity, and inclusion; resource development; communications; and the annual survey. To join the APD, the RPDS, and/or any of our workgroups, please reach out to us or visit the APD website (https://www.dermatologyprofessors.org).

We look forward to welcoming and expediently reviewing members’ submissions to the new Residency Roundup column falling into 2 principal categories within the scope of dermatologic recruitment, didactic education, and clinical training. The first category will feature novel tools, programs, and platforms to improve dermatology training through collaboration. This could entail a description of a new platform designed for sharing resources among programs and specialties to enhance learning for trainees and faculty alike. For example, if a database is created that contains prerecorded lectures pertaining to alopecia, a potential article submission might introduce the database and provide information on what topics are covered and how to access these lectures for readers worldwide. Likewise, if a new technology emerges that allows for easier collaboration among programs, a possible submission would introduce the technology and discuss its potential benefits to trainees, faculty, and practicing dermatologists.

Secondly and more commonly, we anticipate the Residency Roundup column will feature articles that delve into the critical issues and challenges currently impacting recruitment, training, and administration in dermatology residency programs. Specific topics may include but are not limited to recruitment of underrepresented in medicine applicants to dermatology, technological advances to improve teaching methods within training programs, surveys delving into the dermatology match process, and educational gaps or future directions in the specialty. The column occasionally may be used to disseminate information from our section of the APD, including consensus statements or editorials related to changes implemented in the dermatology residency application process. A prospective editorial on this subject could explore varying viewpoints of implemented and proposed changes as well as the reasons behind the changes.

Our group is collaborative, and our aim is to improve education, equity, management of program director responsibilities, and the dermatology application process for programs and applicants alike. With your input, experience, and varied perspectives, we look forward to moving the field of dermatology to a better future by working together. 

To the Editor:

A 44-year-old man with a history of systemic lupus erythematosus (SLE) complicated by lupus nephritis, end-stage renal disease, and antiphospholipid syndrome was evaluated for progressive skin tightening over the last 3 years, predominantly on the hands but also involving the feet, legs, and arms. Physical examination revealed multiple flesh-colored to hypopigmented, bound-down, indurated, fissured plaques over the distal upper and lower extremities, most prominent over the hands (Figure 1). Yellow plaques appeared on the lateral sclera of both eyes (Figure 2). A diagnosis of nephrogenic systemic fibrosis (NSF) was supported by typical findings on punch biopsy, including a proliferation of dermal fibroblasts with thickened collagen bundles and mucin deposition.

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, is characterized by fibrotic plaques and nodules that tend to be bilateral.¹ The chronic course of this disease often is accompanied by flexion contractures. Yellow scleral plaques caused by calcium phosphate deposition are present in up to 75% of cases and are more specific to a diagnosis of NSF in patients younger than 45 years.^1,2 A strong association exists between NSF and gadolinium contrast agents in patients with acute renal failure; our patient later confirmed multiple gadolinium exposures years prior. Deposits of gadolinium have even been found in NSF skin lesions.²

To the Editor:

A 44-year-old man with a history of systemic lupus erythematosus (SLE) complicated by lupus nephritis, end-stage renal disease, and antiphospholipid syndrome was evaluated for progressive skin tightening over the last 3 years, predominantly on the hands but also involving the feet, legs, and arms. Physical examination revealed multiple flesh-colored to hypopigmented, bound-down, indurated, fissured plaques over the distal upper and lower extremities, most prominent over the hands (Figure 1). Yellow plaques appeared on the lateral sclera of both eyes (Figure 2). A diagnosis of nephrogenic systemic fibrosis (NSF) was supported by typical findings on punch biopsy, including a proliferation of dermal fibroblasts with thickened collagen bundles and mucin deposition.

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, is characterized by fibrotic plaques and nodules that tend to be bilateral.¹ The chronic course of this disease often is accompanied by flexion contractures. Yellow scleral plaques caused by calcium phosphate deposition are present in up to 75% of cases and are more specific to a diagnosis of NSF in patients younger than 45 years.^1,2 A strong association exists between NSF and gadolinium contrast agents in patients with acute renal failure; our patient later confirmed multiple gadolinium exposures years prior. Deposits of gadolinium have even been found in NSF skin lesions.²

To the Editor:

A 44-year-old man with a history of systemic lupus erythematosus (SLE) complicated by lupus nephritis, end-stage renal disease, and antiphospholipid syndrome was evaluated for progressive skin tightening over the last 3 years, predominantly on the hands but also involving the feet, legs, and arms. Physical examination revealed multiple flesh-colored to hypopigmented, bound-down, indurated, fissured plaques over the distal upper and lower extremities, most prominent over the hands (Figure 1). Yellow plaques appeared on the lateral sclera of both eyes (Figure 2). A diagnosis of nephrogenic systemic fibrosis (NSF) was supported by typical findings on punch biopsy, including a proliferation of dermal fibroblasts with thickened collagen bundles and mucin deposition.

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, is characterized by fibrotic plaques and nodules that tend to be bilateral.¹ The chronic course of this disease often is accompanied by flexion contractures. Yellow scleral plaques caused by calcium phosphate deposition are present in up to 75% of cases and are more specific to a diagnosis of NSF in patients younger than 45 years.^1,2 A strong association exists between NSF and gadolinium contrast agents in patients with acute renal failure; our patient later confirmed multiple gadolinium exposures years prior. Deposits of gadolinium have even been found in NSF skin lesions.²

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

Regarded as dermatologic emergencies, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of blistering skin diseases that have a high mortality rate. Because of a misguided immune response to medications or infections, CD8⁺ T lymphocytes release proinflammatory cytokines, giving rise to the extensive epidermal destruction seen in SJS and TEN. The exact pathogenesis of SJS and TEN is still poorly defined, but studies have proposed that T cells mediate keratinocyte (KC) apoptosis through perforin and granzyme release and activation of the Fas/Fas ligand (FasL). Functioning as a transmembrane death receptor in the tumor necrosis factor (TNF) superfamily, Fas (CD95) activates Fas-associated death domain protein, caspases, and nucleases, resulting in organized cell destruction. Likewise, perforin and granzymes also have been shown to play a similar role in apoptosis via activation of caspases.¹

Evidence for the role of TNF-α in SJS and TEN has been supported by findings of elevated levels of TNF-α within the blister fluid, serum, and KC cell surface. Additionally, TNF-α has been shown to upregulate inducible nitric oxide synthase in KCs, causing an accumulation of nitric oxide and subsequent FasL-mediated cell death.^1-3 Notably, studies have demonstrated a relative lack of lymphocytes in the tissue of TEN patients despite the extensive destruction that is observed, thus emphasizing the importance of amplification and cell signaling via inflammatory mediators such as TNF-α.¹ In this proposed model, T cells release IFN-γ, causing KCs to release TNF-α that subsequently promotes the upregulation of the aforementioned FasL.¹ Tumor necrosis factor α also may promote increased MHC class I complex deposition on KC surfaces that may play a role in perforin and granzyme-mediated apoptosis of KCs.¹

There is still debate on the standard of care for the treatment of SJS and TEN, attributed to the absence of randomized controlled trials and the rarity of the disease as well as the numerous conflicting studies evaluating potential treatments.^1,4 Despite conflicting data to support their use, supportive care and intravenous immunoglobulin (IVIG) continue to be common treatments for SJS and TEN in hospitals worldwide. Elucidation of the role of TNF-α has prompted the use of infliximab and etanercept. In a case series of Italian patients with TEN (average SCORTEN, 3.6) treated with the TNF-α antagonist etanercept, no mortality was observed, which was well below the calculated expected mortality of 46.9%.² Our retrospective study compared the use of a TNF antagonist to other therapies in the treatment of SJS/TEN. Our data suggest that etanercept is a lifesaving and disease-modifying therapy.

Methods

Twenty-two patients with SJS/TEN were included in this analysis. This included all patients who carried a clinical diagnosis of SJS/TEN with a confirmatory biopsy at our 2 university centers—University of California, Los Angeles, and Keck-LA County-Norris Hospital at the University of Southern California, Los Angeles—from 2013 to 2016. The diagnosis was rendered when a clinical diagnosis of SJS/TEN was given by a dermatologist and a confirmatory biopsy was performed. Every patient given a diagnosis of SJS/TEN at either university system from 2015 onward received an injection of etanercept given the positive results reported by Paradisi et al.²

The 9 patients who presented from 2013 to 2014 to our 2 hospital systems and were given a diagnosis of SJS/TEN received either IVIG or supportive care alone and had an average body surface area (BSA) affected of 23%. The 13 patients who presented from 2015 to 2016 were treated with etanercept in the form of a 50-mg subcutaneous injection given once to the right upper arm. Of this group, 4 patients received dual therapy with both IVIG and etanercept. In the etanercept-treated group (etanercept alone and etanercept plus IVIG), the average BSA affected was 30%. At the time of preliminary diagnosis, all patient medications were evaluated for a possible temporal relationship to the onset of rash and were discontinued if felt to be causative. The causative agent and treatment course for each patient is summarized in Table 1.

Results

A total of 13 patients received etanercept. The mean SCORTEN was 2.2. The observed mortality was 0%, which was markedly lower than the predicted mortality of 24.3% (as determined by linear interpolation). Of this cohort, 9 patients received etanercept alone (mean SCORTEN of 2.1, predicted mortality of 22.9%), whereas 4 patients received a combination of etanercept and IVIG (mean SCORTEN of 2.3, predicted mortality of 27.2%).

The 4 patients who received both etanercept and IVIG received dual therapy for varying reasons. In patient 2 (Table 1), the perceived severity of this case ultimately led to the decision to start IVIG in addition to etanercept, resulting in rapid recovery and discharge after only 1 week of hospitalization. Intravenous immunoglobulin also was given in patient 3 (SCORTEN of 4) and patient 6 (SCORTEN of 2) for progression of disease despite administration of etanercept, with subsequent cessation of progression after the addition of the second agent (IVIG). Patient 12 might have done well on etanercept monotherapy but was administered IVIG as a precautionary measure because of hospital treatment algorithms.

Nine patients did not receive etanercept. Of this group, 5 received IVIG and 4 were managed with supportive care alone. The average SCORTEN for this group was 2.4, only slightly higher than the group that received etanercept (Table 2). The mortality rate in this group was 33%, which was higher than the predicted mortality of 28.1%.

Comment

There is no definitive gold standard treatment of SJS, SJS/TEN overlap, or TEN. However, generally agreed upon management includes immediate discontinuation of the offending medication and supportive therapy with aggressive electrolyte replacement and wound care. Management in a burn unit or intensive care unit is recommended in severe cases. Contention over the efficacy of various medications in the treatment of SJS and TEN continues and largely is due to the rarity of SJS and TEN; studies are small and almost all lack randomization. Therapies that have been used include high-dose steroids, IVIG, plasmapheresis, cyclophosphamide, cyclosporine A, and TNF inhibitors (eg, etanercept, infliximab).¹

Evidence for the use of anti–TNF-α antibodies has been limited thus far, with most of the literature focusing on infliximab and etanercept. Adalimumab, a fully humanized clonal antibody, has no reported cases in the dermatologic literature for use in patients with SJS/TEN. Two case reports of adalimumab paradoxically causing SJS have been documented. In both cases, adalimumab was stopped and patients responded to intravenous corticosteroids and infliximab.^7,8 Similarly, thalidomide has not proven to be a promising anti–TNF-α agent for the treatment of SJS/TEN. In the only attempted randomized controlled trial for SJS and TEN, thalidomide appeared to increase mortality, eventuating in this trial being terminated prior to the planned end date.⁹Infliximab and etanercept have several case reports and a few case series highlighting potentially efficacious application of TNF-α inhibitors for the treatment of SJS/TEN.^10-13 In 2002, Fischer et al¹⁰ reported the first case of TEN treated successfully with a single dose of infliximab 5 mg/kg. Kreft et al¹⁴ reported on etoricoxib-induced TEN that was treated with infliximab 5 mg/kg, which led to re-epithelialization within 5 weeks (notably a 5-week re-epithelialization time is not necessarily an improvement).

In 2005, Hunger et al³ demonstrated TNF-α’s release by KCs in the epidermis and by inflammatory cells in the dermis of a TEN patient. Twenty-four hours after the administration of infliximab 5 mg/kg in these patients, TNF-α was found to be below normal and epidermal detachment ceased.³ Wojtkietwicz et al¹³ demonstrated benefit following an infusion of infliximab 5 mg/kg in a patient whose disease continued to progress despite treatment with dexamethasone and 1.8 g/kg of IVIG.

Then 2 subsequent case series added further support for the efficacy of infliximab in the treatment of TEN. Patmanidis et al¹⁵ and Gaitanis et al¹⁶ reported similar results in 4 patients, each treated with infliximab 5 mg/kg immediately followed by initiation of high-dose IVIG (2 g/kg over 5 days). Zárate-Correa et al¹⁷ reported a 0% mortality rate and near-complete re-epithelialization after 5 to 14 days in 4 patients treated with a single 300-mg dose of infliximab.

However, the success of infliximab in the treatment of TEN has been countered by the pilot study by Paquet et al,¹⁸ which compared the efficacy of 150 mg/kg of N-acetylcysteine alone vs adding infliximab 5 mg/kg to treat 10 TEN patients. The study demonstrated no benefit at 48 hours in the group given infliximab, the time frame in which prior case reports touting infliximab’s benefit claimed the benefit was observed. Similarly, there was no effect on mortality for either treatment modality as assessed by illness auxiliary score.¹⁸

Evidence in support of the use of etanercept in the treatment of SJS/TEN is mounting, and some centers have begun to use it as the first-choice therapy for SJS/TEN. The first case was reported by Famularo et al,¹⁹ in which a patient with TEN was given 2 doses of etanercept 25 mg after failure to improve with prednisolone 1 mg/kg. The patient showed near-complete and rapid re-epithelization in 6 days before death due to disseminated intravascular coagulation 10 days after admission.¹⁹ Gubinelli et al²⁰ and Sadighha²¹ independently reported cases of TEN and TEN/acute generalized exanthematous pustulosis overlap treated with a total of 50 mg of etanercept, demonstrating rapid cessation of lesion progression. Didona et al²² found similar benefit using etanercept 50 mg to treat TEN secondary to rituximab after failure to improve with prednisone and cyclophosphamide. Treatment of TEN with etanercept in an HIV-positive patient also has been reported. Lee et al²³ described a patient who was administered 50-mg and 25-mg injections on days 3 and 5 of hospitalization, respectively, with re-epithelialization occurring by day 8. Finally, Owczarczyk-Saczonek et al²⁴ reported a case of SJS in a patient with a 4-year history of etanercept and sulfasalazine treatment of rheumatoid arthritis; sulfasalazine was stopped, but this patient was continued on etanercept until resolution of skin and mucosal symptoms. However, it is important to consider the possibility of publication bias among these cases selected for their positive outcomes.

Perhaps the most compelling literature regarding the use of etanercept for TEN was described in a case series by Paradisi et al.² This study included 10 patients with TEN, all of whom demonstrated complete re-epithelialization shortly after receiving etanercept 50 mg. Average SCORTEN was 3.6 with a range of 2 to 6. Eight patients in this study had severe comorbidities and all 10 patients survived, with a time to re-epithelialization ranging from 7 to 20 days.² Additionally, a randomized controlled trial showed that 38 etanercept-treated patients had improved mortality (P=.266) and re-epithelialization time (P=.01) compared to patients treated with intravenous methylprednisolone.²⁵Limitations to our study are similar to other reports of SJS/TEN and included the small number of cases and lack of randomization. Additionally, we do not have data available for all patients for time between onset of disease and treatment initiation. Because of these challenges, data presented in this case series is observational only. Additionally, the patients treated with etanercept alone had a slightly lower SCORTEN compared to the group that received IVIG or supportive care alone (2.1 and 2.4 respectively). However, the etanercept-only group actually had higher involvement of epidermal detachment (33%) compared to the non-etanercept group (23%).

Conclusion

Although treatment with etanercept lacks the support of a randomized controlled trial, similar to all other treatments currently used for SJS and TEN, preliminary reports highlight a benefit in disease progression and improvement in time to re-epithelialization. In particular, if etanercept 50 mg subcutaneously is given as monotherapy or is given early in the disease course (prior to other therapies being attempted and ideally within 6 hours of presentation), our data suggest an even greater trend toward improved mortality and decreased time to re-epithelialization. Additionally, our findings may suggest that in some patients, etanercept monotherapy is not an adequate intervention but the addition of IVIG may be helpful; however, the senior author (S.W.) notes anecdotally that in his experience with the patients treated at the University of California Los Angeles, the order of administration of combination therapies—etanercept followed by IVIG—was important in addition to the choice of therapy. These findings are promising enough to warrant a multicenter randomized controlled trial comparing the efficacy of etanercept to other more commonly used treatments for this spectrum of disease, including IVIG and/or cyclosporine. Based on the data presented in this case series, including the 13 patients who received etanercept and had a 0% mortality rate, etanercept may be viewed as a targeted therapeutic intervention for patients with SJS and TEN.

Regarded as dermatologic emergencies, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of blistering skin diseases that have a high mortality rate. Because of a misguided immune response to medications or infections, CD8⁺ T lymphocytes release proinflammatory cytokines, giving rise to the extensive epidermal destruction seen in SJS and TEN. The exact pathogenesis of SJS and TEN is still poorly defined, but studies have proposed that T cells mediate keratinocyte (KC) apoptosis through perforin and granzyme release and activation of the Fas/Fas ligand (FasL). Functioning as a transmembrane death receptor in the tumor necrosis factor (TNF) superfamily, Fas (CD95) activates Fas-associated death domain protein, caspases, and nucleases, resulting in organized cell destruction. Likewise, perforin and granzymes also have been shown to play a similar role in apoptosis via activation of caspases.¹

Evidence for the role of TNF-α in SJS and TEN has been supported by findings of elevated levels of TNF-α within the blister fluid, serum, and KC cell surface. Additionally, TNF-α has been shown to upregulate inducible nitric oxide synthase in KCs, causing an accumulation of nitric oxide and subsequent FasL-mediated cell death.^1-3 Notably, studies have demonstrated a relative lack of lymphocytes in the tissue of TEN patients despite the extensive destruction that is observed, thus emphasizing the importance of amplification and cell signaling via inflammatory mediators such as TNF-α.¹ In this proposed model, T cells release IFN-γ, causing KCs to release TNF-α that subsequently promotes the upregulation of the aforementioned FasL.¹ Tumor necrosis factor α also may promote increased MHC class I complex deposition on KC surfaces that may play a role in perforin and granzyme-mediated apoptosis of KCs.¹

There is still debate on the standard of care for the treatment of SJS and TEN, attributed to the absence of randomized controlled trials and the rarity of the disease as well as the numerous conflicting studies evaluating potential treatments.^1,4 Despite conflicting data to support their use, supportive care and intravenous immunoglobulin (IVIG) continue to be common treatments for SJS and TEN in hospitals worldwide. Elucidation of the role of TNF-α has prompted the use of infliximab and etanercept. In a case series of Italian patients with TEN (average SCORTEN, 3.6) treated with the TNF-α antagonist etanercept, no mortality was observed, which was well below the calculated expected mortality of 46.9%.² Our retrospective study compared the use of a TNF antagonist to other therapies in the treatment of SJS/TEN. Our data suggest that etanercept is a lifesaving and disease-modifying therapy.

Methods

Twenty-two patients with SJS/TEN were included in this analysis. This included all patients who carried a clinical diagnosis of SJS/TEN with a confirmatory biopsy at our 2 university centers—University of California, Los Angeles, and Keck-LA County-Norris Hospital at the University of Southern California, Los Angeles—from 2013 to 2016. The diagnosis was rendered when a clinical diagnosis of SJS/TEN was given by a dermatologist and a confirmatory biopsy was performed. Every patient given a diagnosis of SJS/TEN at either university system from 2015 onward received an injection of etanercept given the positive results reported by Paradisi et al.²

The 9 patients who presented from 2013 to 2014 to our 2 hospital systems and were given a diagnosis of SJS/TEN received either IVIG or supportive care alone and had an average body surface area (BSA) affected of 23%. The 13 patients who presented from 2015 to 2016 were treated with etanercept in the form of a 50-mg subcutaneous injection given once to the right upper arm. Of this group, 4 patients received dual therapy with both IVIG and etanercept. In the etanercept-treated group (etanercept alone and etanercept plus IVIG), the average BSA affected was 30%. At the time of preliminary diagnosis, all patient medications were evaluated for a possible temporal relationship to the onset of rash and were discontinued if felt to be causative. The causative agent and treatment course for each patient is summarized in Table 1.

Results

A total of 13 patients received etanercept. The mean SCORTEN was 2.2. The observed mortality was 0%, which was markedly lower than the predicted mortality of 24.3% (as determined by linear interpolation). Of this cohort, 9 patients received etanercept alone (mean SCORTEN of 2.1, predicted mortality of 22.9%), whereas 4 patients received a combination of etanercept and IVIG (mean SCORTEN of 2.3, predicted mortality of 27.2%).

The 4 patients who received both etanercept and IVIG received dual therapy for varying reasons. In patient 2 (Table 1), the perceived severity of this case ultimately led to the decision to start IVIG in addition to etanercept, resulting in rapid recovery and discharge after only 1 week of hospitalization. Intravenous immunoglobulin also was given in patient 3 (SCORTEN of 4) and patient 6 (SCORTEN of 2) for progression of disease despite administration of etanercept, with subsequent cessation of progression after the addition of the second agent (IVIG). Patient 12 might have done well on etanercept monotherapy but was administered IVIG as a precautionary measure because of hospital treatment algorithms.

Nine patients did not receive etanercept. Of this group, 5 received IVIG and 4 were managed with supportive care alone. The average SCORTEN for this group was 2.4, only slightly higher than the group that received etanercept (Table 2). The mortality rate in this group was 33%, which was higher than the predicted mortality of 28.1%.

Comment

There is no definitive gold standard treatment of SJS, SJS/TEN overlap, or TEN. However, generally agreed upon management includes immediate discontinuation of the offending medication and supportive therapy with aggressive electrolyte replacement and wound care. Management in a burn unit or intensive care unit is recommended in severe cases. Contention over the efficacy of various medications in the treatment of SJS and TEN continues and largely is due to the rarity of SJS and TEN; studies are small and almost all lack randomization. Therapies that have been used include high-dose steroids, IVIG, plasmapheresis, cyclophosphamide, cyclosporine A, and TNF inhibitors (eg, etanercept, infliximab).¹

Evidence for the use of anti–TNF-α antibodies has been limited thus far, with most of the literature focusing on infliximab and etanercept. Adalimumab, a fully humanized clonal antibody, has no reported cases in the dermatologic literature for use in patients with SJS/TEN. Two case reports of adalimumab paradoxically causing SJS have been documented. In both cases, adalimumab was stopped and patients responded to intravenous corticosteroids and infliximab.^7,8 Similarly, thalidomide has not proven to be a promising anti–TNF-α agent for the treatment of SJS/TEN. In the only attempted randomized controlled trial for SJS and TEN, thalidomide appeared to increase mortality, eventuating in this trial being terminated prior to the planned end date.⁹Infliximab and etanercept have several case reports and a few case series highlighting potentially efficacious application of TNF-α inhibitors for the treatment of SJS/TEN.^10-13 In 2002, Fischer et al¹⁰ reported the first case of TEN treated successfully with a single dose of infliximab 5 mg/kg. Kreft et al¹⁴ reported on etoricoxib-induced TEN that was treated with infliximab 5 mg/kg, which led to re-epithelialization within 5 weeks (notably a 5-week re-epithelialization time is not necessarily an improvement).

In 2005, Hunger et al³ demonstrated TNF-α’s release by KCs in the epidermis and by inflammatory cells in the dermis of a TEN patient. Twenty-four hours after the administration of infliximab 5 mg/kg in these patients, TNF-α was found to be below normal and epidermal detachment ceased.³ Wojtkietwicz et al¹³ demonstrated benefit following an infusion of infliximab 5 mg/kg in a patient whose disease continued to progress despite treatment with dexamethasone and 1.8 g/kg of IVIG.

Then 2 subsequent case series added further support for the efficacy of infliximab in the treatment of TEN. Patmanidis et al¹⁵ and Gaitanis et al¹⁶ reported similar results in 4 patients, each treated with infliximab 5 mg/kg immediately followed by initiation of high-dose IVIG (2 g/kg over 5 days). Zárate-Correa et al¹⁷ reported a 0% mortality rate and near-complete re-epithelialization after 5 to 14 days in 4 patients treated with a single 300-mg dose of infliximab.

However, the success of infliximab in the treatment of TEN has been countered by the pilot study by Paquet et al,¹⁸ which compared the efficacy of 150 mg/kg of N-acetylcysteine alone vs adding infliximab 5 mg/kg to treat 10 TEN patients. The study demonstrated no benefit at 48 hours in the group given infliximab, the time frame in which prior case reports touting infliximab’s benefit claimed the benefit was observed. Similarly, there was no effect on mortality for either treatment modality as assessed by illness auxiliary score.¹⁸

Evidence in support of the use of etanercept in the treatment of SJS/TEN is mounting, and some centers have begun to use it as the first-choice therapy for SJS/TEN. The first case was reported by Famularo et al,¹⁹ in which a patient with TEN was given 2 doses of etanercept 25 mg after failure to improve with prednisolone 1 mg/kg. The patient showed near-complete and rapid re-epithelization in 6 days before death due to disseminated intravascular coagulation 10 days after admission.¹⁹ Gubinelli et al²⁰ and Sadighha²¹ independently reported cases of TEN and TEN/acute generalized exanthematous pustulosis overlap treated with a total of 50 mg of etanercept, demonstrating rapid cessation of lesion progression. Didona et al²² found similar benefit using etanercept 50 mg to treat TEN secondary to rituximab after failure to improve with prednisone and cyclophosphamide. Treatment of TEN with etanercept in an HIV-positive patient also has been reported. Lee et al²³ described a patient who was administered 50-mg and 25-mg injections on days 3 and 5 of hospitalization, respectively, with re-epithelialization occurring by day 8. Finally, Owczarczyk-Saczonek et al²⁴ reported a case of SJS in a patient with a 4-year history of etanercept and sulfasalazine treatment of rheumatoid arthritis; sulfasalazine was stopped, but this patient was continued on etanercept until resolution of skin and mucosal symptoms. However, it is important to consider the possibility of publication bias among these cases selected for their positive outcomes.

Perhaps the most compelling literature regarding the use of etanercept for TEN was described in a case series by Paradisi et al.² This study included 10 patients with TEN, all of whom demonstrated complete re-epithelialization shortly after receiving etanercept 50 mg. Average SCORTEN was 3.6 with a range of 2 to 6. Eight patients in this study had severe comorbidities and all 10 patients survived, with a time to re-epithelialization ranging from 7 to 20 days.² Additionally, a randomized controlled trial showed that 38 etanercept-treated patients had improved mortality (P=.266) and re-epithelialization time (P=.01) compared to patients treated with intravenous methylprednisolone.²⁵Limitations to our study are similar to other reports of SJS/TEN and included the small number of cases and lack of randomization. Additionally, we do not have data available for all patients for time between onset of disease and treatment initiation. Because of these challenges, data presented in this case series is observational only. Additionally, the patients treated with etanercept alone had a slightly lower SCORTEN compared to the group that received IVIG or supportive care alone (2.1 and 2.4 respectively). However, the etanercept-only group actually had higher involvement of epidermal detachment (33%) compared to the non-etanercept group (23%).

Conclusion

Although treatment with etanercept lacks the support of a randomized controlled trial, similar to all other treatments currently used for SJS and TEN, preliminary reports highlight a benefit in disease progression and improvement in time to re-epithelialization. In particular, if etanercept 50 mg subcutaneously is given as monotherapy or is given early in the disease course (prior to other therapies being attempted and ideally within 6 hours of presentation), our data suggest an even greater trend toward improved mortality and decreased time to re-epithelialization. Additionally, our findings may suggest that in some patients, etanercept monotherapy is not an adequate intervention but the addition of IVIG may be helpful; however, the senior author (S.W.) notes anecdotally that in his experience with the patients treated at the University of California Los Angeles, the order of administration of combination therapies—etanercept followed by IVIG—was important in addition to the choice of therapy. These findings are promising enough to warrant a multicenter randomized controlled trial comparing the efficacy of etanercept to other more commonly used treatments for this spectrum of disease, including IVIG and/or cyclosporine. Based on the data presented in this case series, including the 13 patients who received etanercept and had a 0% mortality rate, etanercept may be viewed as a targeted therapeutic intervention for patients with SJS and TEN.

Regarded as dermatologic emergencies, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of blistering skin diseases that have a high mortality rate. Because of a misguided immune response to medications or infections, CD8⁺ T lymphocytes release proinflammatory cytokines, giving rise to the extensive epidermal destruction seen in SJS and TEN. The exact pathogenesis of SJS and TEN is still poorly defined, but studies have proposed that T cells mediate keratinocyte (KC) apoptosis through perforin and granzyme release and activation of the Fas/Fas ligand (FasL). Functioning as a transmembrane death receptor in the tumor necrosis factor (TNF) superfamily, Fas (CD95) activates Fas-associated death domain protein, caspases, and nucleases, resulting in organized cell destruction. Likewise, perforin and granzymes also have been shown to play a similar role in apoptosis via activation of caspases.¹

Evidence for the role of TNF-α in SJS and TEN has been supported by findings of elevated levels of TNF-α within the blister fluid, serum, and KC cell surface. Additionally, TNF-α has been shown to upregulate inducible nitric oxide synthase in KCs, causing an accumulation of nitric oxide and subsequent FasL-mediated cell death.^1-3 Notably, studies have demonstrated a relative lack of lymphocytes in the tissue of TEN patients despite the extensive destruction that is observed, thus emphasizing the importance of amplification and cell signaling via inflammatory mediators such as TNF-α.¹ In this proposed model, T cells release IFN-γ, causing KCs to release TNF-α that subsequently promotes the upregulation of the aforementioned FasL.¹ Tumor necrosis factor α also may promote increased MHC class I complex deposition on KC surfaces that may play a role in perforin and granzyme-mediated apoptosis of KCs.¹

There is still debate on the standard of care for the treatment of SJS and TEN, attributed to the absence of randomized controlled trials and the rarity of the disease as well as the numerous conflicting studies evaluating potential treatments.^1,4 Despite conflicting data to support their use, supportive care and intravenous immunoglobulin (IVIG) continue to be common treatments for SJS and TEN in hospitals worldwide. Elucidation of the role of TNF-α has prompted the use of infliximab and etanercept. In a case series of Italian patients with TEN (average SCORTEN, 3.6) treated with the TNF-α antagonist etanercept, no mortality was observed, which was well below the calculated expected mortality of 46.9%.² Our retrospective study compared the use of a TNF antagonist to other therapies in the treatment of SJS/TEN. Our data suggest that etanercept is a lifesaving and disease-modifying therapy.

Methods

Twenty-two patients with SJS/TEN were included in this analysis. This included all patients who carried a clinical diagnosis of SJS/TEN with a confirmatory biopsy at our 2 university centers—University of California, Los Angeles, and Keck-LA County-Norris Hospital at the University of Southern California, Los Angeles—from 2013 to 2016. The diagnosis was rendered when a clinical diagnosis of SJS/TEN was given by a dermatologist and a confirmatory biopsy was performed. Every patient given a diagnosis of SJS/TEN at either university system from 2015 onward received an injection of etanercept given the positive results reported by Paradisi et al.²

The 9 patients who presented from 2013 to 2014 to our 2 hospital systems and were given a diagnosis of SJS/TEN received either IVIG or supportive care alone and had an average body surface area (BSA) affected of 23%. The 13 patients who presented from 2015 to 2016 were treated with etanercept in the form of a 50-mg subcutaneous injection given once to the right upper arm. Of this group, 4 patients received dual therapy with both IVIG and etanercept. In the etanercept-treated group (etanercept alone and etanercept plus IVIG), the average BSA affected was 30%. At the time of preliminary diagnosis, all patient medications were evaluated for a possible temporal relationship to the onset of rash and were discontinued if felt to be causative. The causative agent and treatment course for each patient is summarized in Table 1.

Results

A total of 13 patients received etanercept. The mean SCORTEN was 2.2. The observed mortality was 0%, which was markedly lower than the predicted mortality of 24.3% (as determined by linear interpolation). Of this cohort, 9 patients received etanercept alone (mean SCORTEN of 2.1, predicted mortality of 22.9%), whereas 4 patients received a combination of etanercept and IVIG (mean SCORTEN of 2.3, predicted mortality of 27.2%).

The 4 patients who received both etanercept and IVIG received dual therapy for varying reasons. In patient 2 (Table 1), the perceived severity of this case ultimately led to the decision to start IVIG in addition to etanercept, resulting in rapid recovery and discharge after only 1 week of hospitalization. Intravenous immunoglobulin also was given in patient 3 (SCORTEN of 4) and patient 6 (SCORTEN of 2) for progression of disease despite administration of etanercept, with subsequent cessation of progression after the addition of the second agent (IVIG). Patient 12 might have done well on etanercept monotherapy but was administered IVIG as a precautionary measure because of hospital treatment algorithms.

Nine patients did not receive etanercept. Of this group, 5 received IVIG and 4 were managed with supportive care alone. The average SCORTEN for this group was 2.4, only slightly higher than the group that received etanercept (Table 2). The mortality rate in this group was 33%, which was higher than the predicted mortality of 28.1%.

Comment

There is no definitive gold standard treatment of SJS, SJS/TEN overlap, or TEN. However, generally agreed upon management includes immediate discontinuation of the offending medication and supportive therapy with aggressive electrolyte replacement and wound care. Management in a burn unit or intensive care unit is recommended in severe cases. Contention over the efficacy of various medications in the treatment of SJS and TEN continues and largely is due to the rarity of SJS and TEN; studies are small and almost all lack randomization. Therapies that have been used include high-dose steroids, IVIG, plasmapheresis, cyclophosphamide, cyclosporine A, and TNF inhibitors (eg, etanercept, infliximab).¹

Evidence for the use of anti–TNF-α antibodies has been limited thus far, with most of the literature focusing on infliximab and etanercept. Adalimumab, a fully humanized clonal antibody, has no reported cases in the dermatologic literature for use in patients with SJS/TEN. Two case reports of adalimumab paradoxically causing SJS have been documented. In both cases, adalimumab was stopped and patients responded to intravenous corticosteroids and infliximab.^7,8 Similarly, thalidomide has not proven to be a promising anti–TNF-α agent for the treatment of SJS/TEN. In the only attempted randomized controlled trial for SJS and TEN, thalidomide appeared to increase mortality, eventuating in this trial being terminated prior to the planned end date.⁹Infliximab and etanercept have several case reports and a few case series highlighting potentially efficacious application of TNF-α inhibitors for the treatment of SJS/TEN.^10-13 In 2002, Fischer et al¹⁰ reported the first case of TEN treated successfully with a single dose of infliximab 5 mg/kg. Kreft et al¹⁴ reported on etoricoxib-induced TEN that was treated with infliximab 5 mg/kg, which led to re-epithelialization within 5 weeks (notably a 5-week re-epithelialization time is not necessarily an improvement).

In 2005, Hunger et al³ demonstrated TNF-α’s release by KCs in the epidermis and by inflammatory cells in the dermis of a TEN patient. Twenty-four hours after the administration of infliximab 5 mg/kg in these patients, TNF-α was found to be below normal and epidermal detachment ceased.³ Wojtkietwicz et al¹³ demonstrated benefit following an infusion of infliximab 5 mg/kg in a patient whose disease continued to progress despite treatment with dexamethasone and 1.8 g/kg of IVIG.

Then 2 subsequent case series added further support for the efficacy of infliximab in the treatment of TEN. Patmanidis et al¹⁵ and Gaitanis et al¹⁶ reported similar results in 4 patients, each treated with infliximab 5 mg/kg immediately followed by initiation of high-dose IVIG (2 g/kg over 5 days). Zárate-Correa et al¹⁷ reported a 0% mortality rate and near-complete re-epithelialization after 5 to 14 days in 4 patients treated with a single 300-mg dose of infliximab.

However, the success of infliximab in the treatment of TEN has been countered by the pilot study by Paquet et al,¹⁸ which compared the efficacy of 150 mg/kg of N-acetylcysteine alone vs adding infliximab 5 mg/kg to treat 10 TEN patients. The study demonstrated no benefit at 48 hours in the group given infliximab, the time frame in which prior case reports touting infliximab’s benefit claimed the benefit was observed. Similarly, there was no effect on mortality for either treatment modality as assessed by illness auxiliary score.¹⁸

Evidence in support of the use of etanercept in the treatment of SJS/TEN is mounting, and some centers have begun to use it as the first-choice therapy for SJS/TEN. The first case was reported by Famularo et al,¹⁹ in which a patient with TEN was given 2 doses of etanercept 25 mg after failure to improve with prednisolone 1 mg/kg. The patient showed near-complete and rapid re-epithelization in 6 days before death due to disseminated intravascular coagulation 10 days after admission.¹⁹ Gubinelli et al²⁰ and Sadighha²¹ independently reported cases of TEN and TEN/acute generalized exanthematous pustulosis overlap treated with a total of 50 mg of etanercept, demonstrating rapid cessation of lesion progression. Didona et al²² found similar benefit using etanercept 50 mg to treat TEN secondary to rituximab after failure to improve with prednisone and cyclophosphamide. Treatment of TEN with etanercept in an HIV-positive patient also has been reported. Lee et al²³ described a patient who was administered 50-mg and 25-mg injections on days 3 and 5 of hospitalization, respectively, with re-epithelialization occurring by day 8. Finally, Owczarczyk-Saczonek et al²⁴ reported a case of SJS in a patient with a 4-year history of etanercept and sulfasalazine treatment of rheumatoid arthritis; sulfasalazine was stopped, but this patient was continued on etanercept until resolution of skin and mucosal symptoms. However, it is important to consider the possibility of publication bias among these cases selected for their positive outcomes.

Perhaps the most compelling literature regarding the use of etanercept for TEN was described in a case series by Paradisi et al.² This study included 10 patients with TEN, all of whom demonstrated complete re-epithelialization shortly after receiving etanercept 50 mg. Average SCORTEN was 3.6 with a range of 2 to 6. Eight patients in this study had severe comorbidities and all 10 patients survived, with a time to re-epithelialization ranging from 7 to 20 days.² Additionally, a randomized controlled trial showed that 38 etanercept-treated patients had improved mortality (P=.266) and re-epithelialization time (P=.01) compared to patients treated with intravenous methylprednisolone.²⁵Limitations to our study are similar to other reports of SJS/TEN and included the small number of cases and lack of randomization. Additionally, we do not have data available for all patients for time between onset of disease and treatment initiation. Because of these challenges, data presented in this case series is observational only. Additionally, the patients treated with etanercept alone had a slightly lower SCORTEN compared to the group that received IVIG or supportive care alone (2.1 and 2.4 respectively). However, the etanercept-only group actually had higher involvement of epidermal detachment (33%) compared to the non-etanercept group (23%).

Conclusion

Although treatment with etanercept lacks the support of a randomized controlled trial, similar to all other treatments currently used for SJS and TEN, preliminary reports highlight a benefit in disease progression and improvement in time to re-epithelialization. In particular, if etanercept 50 mg subcutaneously is given as monotherapy or is given early in the disease course (prior to other therapies being attempted and ideally within 6 hours of presentation), our data suggest an even greater trend toward improved mortality and decreased time to re-epithelialization. Additionally, our findings may suggest that in some patients, etanercept monotherapy is not an adequate intervention but the addition of IVIG may be helpful; however, the senior author (S.W.) notes anecdotally that in his experience with the patients treated at the University of California Los Angeles, the order of administration of combination therapies—etanercept followed by IVIG—was important in addition to the choice of therapy. These findings are promising enough to warrant a multicenter randomized controlled trial comparing the efficacy of etanercept to other more commonly used treatments for this spectrum of disease, including IVIG and/or cyclosporine. Based on the data presented in this case series, including the 13 patients who received etanercept and had a 0% mortality rate, etanercept may be viewed as a targeted therapeutic intervention for patients with SJS and TEN.

To the Editor:

Relapsing polychondritis (RP) is a chronic, progressive, and episodic systemic inflammatory disease that primarily affects the cartilaginous structures of the ears and nose. Involvement of other proteoglycan-rich structures such as the joints, eyes, inner ears, blood vessels, heart, and kidneys also may be seen. Dermatologic manifestations occur in 35% to 50% of patients and may be the presenting sign in up to 12% of cases.¹ The most commonly reported dermatologic findings include oral aphthosis, erythema nodosum, and purpura with vasculitic changes. Less commonly reported associations include Sweet syndrome, pyoderma gangrenosum, panniculitis, erythema elevatum diutinum, erythema annulare centrifugum, and erythema multiforme.¹

A 43-year-old woman who was otherwise healthy developed new-onset tenderness and swelling of the left pinna while on vacation. She was treated with trimethoprim-sulfamethoxazole, clindamycin, and levofloxacin for presumed auricular cellulitis. The patient developed a fever; sore throat; and a progressive, pruritic, blistering rash on the face, torso, bilateral extremities, palms, and soles 1 day after completing the antibiotic course. After 5 days of unremitting symptoms despite oral, intramuscular, and topical steroids, the patient presented to the emergency department. Physical examination revealed diffuse, tender, erythematous to violaceous macules with varying degrees of coalescence on the chest, back, and extremities. Scattered flaccid bullae and erosions of the oral and genital mucosa also were seen. Laboratory analysis was notable only for a urinary tract infection with Klebsiella pneumoniae. A punch biopsy demonstrated full-thickness necrosis of the epidermis with subepidermal bullae and a mild to moderate lymphocytic infiltrate with rare eosinophils, consistent with a diagnosis of Stevens-Johnson syndrome (SJS). Because of the body surface area involved (20%) and the recent history of trimethoprim-sulfamethoxazole use, a diagnosis of SJS/toxic epidermal necrolysis (TEN) overlap syndrome was made. The patient was successfully treated with subcutaneous etanercept (50 mg), supportive care, and cephalexin for the urinary tract infection.

Approximately 5 weeks after discharge from the hospital, the patient was evaluated for new-onset pain and swelling of the right ear (Figure) in conjunction with recent tenderness and depression of the superior septal structure of the nose. A punch biopsy of the ear revealed mild perichondral inflammation without vasculitic changes and a superficial, deep perivascular, and periadnexal lymphoplasmacytic inflammatory infiltrate with scattered eosinophils. A diagnosis of RP was made, as the patient met Damiani and Levine’s² criteria with bilateral auricular inflammation, ocular inflammation, and nasal chondritis.

We report a unique case of SJS/TEN overlap syndrome occurring in a patient with RP.¹ Although the association may be coincidental, it is well known that patients with lupus erythematosus are predisposed to the development of SJS and TEN. Therefore, a shared underlying genetic predisposition or immune system hyperactivity secondary to active RP is a possible explanation for our patient’s unique presentation.

To the Editor:

Relapsing polychondritis (RP) is a chronic, progressive, and episodic systemic inflammatory disease that primarily affects the cartilaginous structures of the ears and nose. Involvement of other proteoglycan-rich structures such as the joints, eyes, inner ears, blood vessels, heart, and kidneys also may be seen. Dermatologic manifestations occur in 35% to 50% of patients and may be the presenting sign in up to 12% of cases.¹ The most commonly reported dermatologic findings include oral aphthosis, erythema nodosum, and purpura with vasculitic changes. Less commonly reported associations include Sweet syndrome, pyoderma gangrenosum, panniculitis, erythema elevatum diutinum, erythema annulare centrifugum, and erythema multiforme.¹

A 43-year-old woman who was otherwise healthy developed new-onset tenderness and swelling of the left pinna while on vacation. She was treated with trimethoprim-sulfamethoxazole, clindamycin, and levofloxacin for presumed auricular cellulitis. The patient developed a fever; sore throat; and a progressive, pruritic, blistering rash on the face, torso, bilateral extremities, palms, and soles 1 day after completing the antibiotic course. After 5 days of unremitting symptoms despite oral, intramuscular, and topical steroids, the patient presented to the emergency department. Physical examination revealed diffuse, tender, erythematous to violaceous macules with varying degrees of coalescence on the chest, back, and extremities. Scattered flaccid bullae and erosions of the oral and genital mucosa also were seen. Laboratory analysis was notable only for a urinary tract infection with Klebsiella pneumoniae. A punch biopsy demonstrated full-thickness necrosis of the epidermis with subepidermal bullae and a mild to moderate lymphocytic infiltrate with rare eosinophils, consistent with a diagnosis of Stevens-Johnson syndrome (SJS). Because of the body surface area involved (20%) and the recent history of trimethoprim-sulfamethoxazole use, a diagnosis of SJS/toxic epidermal necrolysis (TEN) overlap syndrome was made. The patient was successfully treated with subcutaneous etanercept (50 mg), supportive care, and cephalexin for the urinary tract infection.

Approximately 5 weeks after discharge from the hospital, the patient was evaluated for new-onset pain and swelling of the right ear (Figure) in conjunction with recent tenderness and depression of the superior septal structure of the nose. A punch biopsy of the ear revealed mild perichondral inflammation without vasculitic changes and a superficial, deep perivascular, and periadnexal lymphoplasmacytic inflammatory infiltrate with scattered eosinophils. A diagnosis of RP was made, as the patient met Damiani and Levine’s² criteria with bilateral auricular inflammation, ocular inflammation, and nasal chondritis.

We report a unique case of SJS/TEN overlap syndrome occurring in a patient with RP.¹ Although the association may be coincidental, it is well known that patients with lupus erythematosus are predisposed to the development of SJS and TEN. Therefore, a shared underlying genetic predisposition or immune system hyperactivity secondary to active RP is a possible explanation for our patient’s unique presentation.

To the Editor:

Relapsing polychondritis (RP) is a chronic, progressive, and episodic systemic inflammatory disease that primarily affects the cartilaginous structures of the ears and nose. Involvement of other proteoglycan-rich structures such as the joints, eyes, inner ears, blood vessels, heart, and kidneys also may be seen. Dermatologic manifestations occur in 35% to 50% of patients and may be the presenting sign in up to 12% of cases.¹ The most commonly reported dermatologic findings include oral aphthosis, erythema nodosum, and purpura with vasculitic changes. Less commonly reported associations include Sweet syndrome, pyoderma gangrenosum, panniculitis, erythema elevatum diutinum, erythema annulare centrifugum, and erythema multiforme.¹

A 43-year-old woman who was otherwise healthy developed new-onset tenderness and swelling of the left pinna while on vacation. She was treated with trimethoprim-sulfamethoxazole, clindamycin, and levofloxacin for presumed auricular cellulitis. The patient developed a fever; sore throat; and a progressive, pruritic, blistering rash on the face, torso, bilateral extremities, palms, and soles 1 day after completing the antibiotic course. After 5 days of unremitting symptoms despite oral, intramuscular, and topical steroids, the patient presented to the emergency department. Physical examination revealed diffuse, tender, erythematous to violaceous macules with varying degrees of coalescence on the chest, back, and extremities. Scattered flaccid bullae and erosions of the oral and genital mucosa also were seen. Laboratory analysis was notable only for a urinary tract infection with Klebsiella pneumoniae. A punch biopsy demonstrated full-thickness necrosis of the epidermis with subepidermal bullae and a mild to moderate lymphocytic infiltrate with rare eosinophils, consistent with a diagnosis of Stevens-Johnson syndrome (SJS). Because of the body surface area involved (20%) and the recent history of trimethoprim-sulfamethoxazole use, a diagnosis of SJS/toxic epidermal necrolysis (TEN) overlap syndrome was made. The patient was successfully treated with subcutaneous etanercept (50 mg), supportive care, and cephalexin for the urinary tract infection.

Approximately 5 weeks after discharge from the hospital, the patient was evaluated for new-onset pain and swelling of the right ear (Figure) in conjunction with recent tenderness and depression of the superior septal structure of the nose. A punch biopsy of the ear revealed mild perichondral inflammation without vasculitic changes and a superficial, deep perivascular, and periadnexal lymphoplasmacytic inflammatory infiltrate with scattered eosinophils. A diagnosis of RP was made, as the patient met Damiani and Levine’s² criteria with bilateral auricular inflammation, ocular inflammation, and nasal chondritis.

We report a unique case of SJS/TEN overlap syndrome occurring in a patient with RP.¹ Although the association may be coincidental, it is well known that patients with lupus erythematosus are predisposed to the development of SJS and TEN. Therefore, a shared underlying genetic predisposition or immune system hyperactivity secondary to active RP is a possible explanation for our patient’s unique presentation.

The #MeToo movement that took hold in the wake of the Harvey Weinstein allegations in 2017 likely will be considered one of the major cultural touchpoints of the 2010s. Although activism within the entertainment industry initially drew attention to this movement, it is understood that virtually no workplace is immune to sexual misconduct. Many medical professionals acknowledge #MeToo as a catchy hashtag summarizing a problem that has long been recognized in the field of medicine but often has been inadequately addressed.¹ As dermatology residency program directors (PDs) at the University of Southern California (USC) Keck School of Medicine (Los Angeles, California), we have seen the considerable impact that recent high-profile allegations of sexual assault have had at our institution, leading us to take part in institutional and departmental initiatives and reflections that we believe have strengthened the culture within our residency program and positioned us to be proactive in addressing this critical issue.

Before we discuss the efforts to combat sexual misconduct and gender inequality at USC and within our dermatology department, it is worth reflecting on where we stand as a specialty with regard to gender representation. A recent JAMA Dermatology article reported that in 1970 only 10.8% of dermatology academic faculty were women but by 2018 that number had skyrocketed to 51.2%; however, in contrast to this overall increase, only 19.4% of dermatology department chairs in 2018 were women.² Although we have made large strides as a field, this discrepancy indicates that we still have a long way to go to achieve gender equality.

Although dermatology as a specialty is working toward gender equality, we believe it is crucial to consider this issue in the context of the entire field of medicine, particularly because academic physicians and trainees often interface with a myriad of specialties. It is well known that women in medicine are more likely to be victims of sexual harassment or assault in the workplace and that subsequent issues with imposter syndrome and/or depression are more prevalent in female physicians.^3,4 Gender inequality and sexism, among other factors, can make it difficult for women to obtain and maintain leadership positions and can negatively impact the culture of an academic institution in numerous downstream ways.

We also know that academic environments in medicine have a higher prevalence of gender equality issues than in private practice or in settings where medicine is practiced without trainees due to the hierarchical nature of training and the necessary differences in experience between trainees and faculty.³ Furthermore, because trainees form and solidify their professional identities during graduate medical education (GME) training, it is a prime time to emphasize the importance of gender equality and establish zero tolerance policies for workplace abuse and transgressions.⁵

The data and our personal experiences delineate a clear need for continued vigilance regarding gender equality issues both in dermatology as a specialty and in medicine in general. As PDs, we feel fortunate to have worked in conjunction with our GME committee and our dermatology department to solidify and create policies that work to promote a culture of gender equality. Herein, we will outline some of these efforts with the hope that other academic institutions may consider implementing these programs to protect members of their community from harassment, sexual violence, and gender discrimination.

Create a SAFE Committee

At the institutional level, our GME committee has created the SAFE (Safety, Fairness & Equity) committee under the leadership of Lawrence Opas, MD. The SAFE committee is headed by a female faculty physician and includes members of the medical community who have the influence to affect change and a commitment to protect vulnerable populations. Members include the Chief Medical Officer, the Designated Institutional Officer, the Director of Resident Wellness, and the Dean of the Keck School of Medicine at USC. The SAFE committee serves as a 24/7 reporting resource whereby trainees can report any issues relating to harassment in the workplace via a telephone hotline or online platform. Issues brought to this committee are immediately dealt with and reviewed at monthly GME meetings to keep institutional PDs up-to-date on issues pertaining to sexual harassment and assault within our workplace. The SAFE committee also has departmental resident liaisons who bring information to residents and help guide them to appropriate resources.

Emphasize Resident Wellness

Along with the development of robust reporting resources, our institution has continued to build upon a culture that places a strong emphasis on resident wellness. One of the most meaningful efforts over the last 5 years has included recruitment of a clinical psychologist, Tobi Fishel, PhD, to serve as our institution’s Director of Wellness. She is available to meet confidentially with our residents and helps to serve as a link between trainees and the GME committee.

Our dermatology department takes a tremendous amount of pride in its culture. We are fortunate to have David Peng, MD, MPH, Chair, and Stefani Takahashi, MD, Vice Chair of Education, working daily to create an environment that values teamwork, selflessness, and wellness. We have been continuously grateful for their leadership and guidance in addressing the allegations of sexual assault and harassment that arose at USC over the past several years. Our department has a zero tolerance policy for sexual harassment or harassment of any kind, and we have taken important steps to ensure and promote a safe environment for our trainees, many of which are focused on communication. We try to avoid assumptions and encourage both residents and faculty to explicitly state their experiences and opinions in general but also in relation to instances of potential misconduct.

Encourage Communication

When allegations of sexual misconduct in the workplace were made at our institution, we prioritized immediate in-person communication with our residents to reinforce our zero tolerance policy and to remind them that we are available should any similar issues arise in our department. It was of equal value to remind our trainees of potential resources, such as the SAFE committee, to whom they could bring their concerns if they were not comfortable communicating directly with us. Although we hoped that our trainees understood that we would not be tolerant of any form of harassment based on our past actions and communications, we felt that it was helpful to explicitly delineate this by laying out other avenues of support on a regular basis with them. By ensuring there is a space for a dialogue with others, if needed, our institution and department have provided an extra layer of security for our trainees. Multiple channels of support are crucial to ensure trainee safety.

Dr. Peng also created a workplace safety committee that includes several female faculty members. The committee regularly shares and highlights institutional and departmental resources as they pertain to gender equality and safety within the workplace and also has considerable faculty overlap with our departmental diversity committee. Together, these committees work toward the common goal of fostering an environment in which all members of our department feel comfortable voicing concerns, and we are best able to recruit and retain a diverse faculty.

As PDs, we work to reinforce departmental and institutional messages in our daily communication with residents. We have found that ensuring frequent and varied interactions—quarterly meetings, biannual evaluations, faculty-led didactics 2 half-days per week, and weekly clinical interactions—with our trainees can help to create a culture where they feel comfortable bringing up issues, be they routine clinical operations questions or issues relating to their professional identity. We hope it also has created the space for them to approach us with any issues pertaining to harassment should they ever arise, and we are grateful to know that even if this comfort does not exist, our institution and department have other resources for them.

Final Thoughts

Although some of the measures discussed here were reactionary, many predated the recent institutional concerns and allegations at USC. We hope and believe that the culture we foster within our department has helped our trainees feel safe and cared for during a time of institutional turbulence. We also believe that taking similar proactive measures may benefit the overall culture and foster the development of diverse physicians and leadership at other institutions. In conjunction with reworking legislation and implementing institutional safeguards, the long-term goals of taking these proactive measures are to promote gender equality and workplace safety and to cultivate and retain effective female leadership in medical institutions and training programs.

We feel incredibly fortunate to be part of a specialty in which gender equality has long been considered and sought after. We also are proud to be members of the Association of Professors of Dermatology, which has addressed issues such as diversity and gender equality in a transparent and head-on manner and continues to do so. As a specialty, we hope we can support our trainees in their professional growth and help to cultivate sensitive physicians who will care for an increasingly diverse population and better support each other in their own career development.

The #MeToo movement that took hold in the wake of the Harvey Weinstein allegations in 2017 likely will be considered one of the major cultural touchpoints of the 2010s. Although activism within the entertainment industry initially drew attention to this movement, it is understood that virtually no workplace is immune to sexual misconduct. Many medical professionals acknowledge #MeToo as a catchy hashtag summarizing a problem that has long been recognized in the field of medicine but often has been inadequately addressed.¹ As dermatology residency program directors (PDs) at the University of Southern California (USC) Keck School of Medicine (Los Angeles, California), we have seen the considerable impact that recent high-profile allegations of sexual assault have had at our institution, leading us to take part in institutional and departmental initiatives and reflections that we believe have strengthened the culture within our residency program and positioned us to be proactive in addressing this critical issue.

Before we discuss the efforts to combat sexual misconduct and gender inequality at USC and within our dermatology department, it is worth reflecting on where we stand as a specialty with regard to gender representation. A recent JAMA Dermatology article reported that in 1970 only 10.8% of dermatology academic faculty were women but by 2018 that number had skyrocketed to 51.2%; however, in contrast to this overall increase, only 19.4% of dermatology department chairs in 2018 were women.² Although we have made large strides as a field, this discrepancy indicates that we still have a long way to go to achieve gender equality.

Although dermatology as a specialty is working toward gender equality, we believe it is crucial to consider this issue in the context of the entire field of medicine, particularly because academic physicians and trainees often interface with a myriad of specialties. It is well known that women in medicine are more likely to be victims of sexual harassment or assault in the workplace and that subsequent issues with imposter syndrome and/or depression are more prevalent in female physicians.^3,4 Gender inequality and sexism, among other factors, can make it difficult for women to obtain and maintain leadership positions and can negatively impact the culture of an academic institution in numerous downstream ways.

We also know that academic environments in medicine have a higher prevalence of gender equality issues than in private practice or in settings where medicine is practiced without trainees due to the hierarchical nature of training and the necessary differences in experience between trainees and faculty.³ Furthermore, because trainees form and solidify their professional identities during graduate medical education (GME) training, it is a prime time to emphasize the importance of gender equality and establish zero tolerance policies for workplace abuse and transgressions.⁵

The data and our personal experiences delineate a clear need for continued vigilance regarding gender equality issues both in dermatology as a specialty and in medicine in general. As PDs, we feel fortunate to have worked in conjunction with our GME committee and our dermatology department to solidify and create policies that work to promote a culture of gender equality. Herein, we will outline some of these efforts with the hope that other academic institutions may consider implementing these programs to protect members of their community from harassment, sexual violence, and gender discrimination.

Create a SAFE Committee

At the institutional level, our GME committee has created the SAFE (Safety, Fairness & Equity) committee under the leadership of Lawrence Opas, MD. The SAFE committee is headed by a female faculty physician and includes members of the medical community who have the influence to affect change and a commitment to protect vulnerable populations. Members include the Chief Medical Officer, the Designated Institutional Officer, the Director of Resident Wellness, and the Dean of the Keck School of Medicine at USC. The SAFE committee serves as a 24/7 reporting resource whereby trainees can report any issues relating to harassment in the workplace via a telephone hotline or online platform. Issues brought to this committee are immediately dealt with and reviewed at monthly GME meetings to keep institutional PDs up-to-date on issues pertaining to sexual harassment and assault within our workplace. The SAFE committee also has departmental resident liaisons who bring information to residents and help guide them to appropriate resources.

Emphasize Resident Wellness

Along with the development of robust reporting resources, our institution has continued to build upon a culture that places a strong emphasis on resident wellness. One of the most meaningful efforts over the last 5 years has included recruitment of a clinical psychologist, Tobi Fishel, PhD, to serve as our institution’s Director of Wellness. She is available to meet confidentially with our residents and helps to serve as a link between trainees and the GME committee.

Our dermatology department takes a tremendous amount of pride in its culture. We are fortunate to have David Peng, MD, MPH, Chair, and Stefani Takahashi, MD, Vice Chair of Education, working daily to create an environment that values teamwork, selflessness, and wellness. We have been continuously grateful for their leadership and guidance in addressing the allegations of sexual assault and harassment that arose at USC over the past several years. Our department has a zero tolerance policy for sexual harassment or harassment of any kind, and we have taken important steps to ensure and promote a safe environment for our trainees, many of which are focused on communication. We try to avoid assumptions and encourage both residents and faculty to explicitly state their experiences and opinions in general but also in relation to instances of potential misconduct.

Encourage Communication

When allegations of sexual misconduct in the workplace were made at our institution, we prioritized immediate in-person communication with our residents to reinforce our zero tolerance policy and to remind them that we are available should any similar issues arise in our department. It was of equal value to remind our trainees of potential resources, such as the SAFE committee, to whom they could bring their concerns if they were not comfortable communicating directly with us. Although we hoped that our trainees understood that we would not be tolerant of any form of harassment based on our past actions and communications, we felt that it was helpful to explicitly delineate this by laying out other avenues of support on a regular basis with them. By ensuring there is a space for a dialogue with others, if needed, our institution and department have provided an extra layer of security for our trainees. Multiple channels of support are crucial to ensure trainee safety.

Dr. Peng also created a workplace safety committee that includes several female faculty members. The committee regularly shares and highlights institutional and departmental resources as they pertain to gender equality and safety within the workplace and also has considerable faculty overlap with our departmental diversity committee. Together, these committees work toward the common goal of fostering an environment in which all members of our department feel comfortable voicing concerns, and we are best able to recruit and retain a diverse faculty.

As PDs, we work to reinforce departmental and institutional messages in our daily communication with residents. We have found that ensuring frequent and varied interactions—quarterly meetings, biannual evaluations, faculty-led didactics 2 half-days per week, and weekly clinical interactions—with our trainees can help to create a culture where they feel comfortable bringing up issues, be they routine clinical operations questions or issues relating to their professional identity. We hope it also has created the space for them to approach us with any issues pertaining to harassment should they ever arise, and we are grateful to know that even if this comfort does not exist, our institution and department have other resources for them.

Final Thoughts

Although some of the measures discussed here were reactionary, many predated the recent institutional concerns and allegations at USC. We hope and believe that the culture we foster within our department has helped our trainees feel safe and cared for during a time of institutional turbulence. We also believe that taking similar proactive measures may benefit the overall culture and foster the development of diverse physicians and leadership at other institutions. In conjunction with reworking legislation and implementing institutional safeguards, the long-term goals of taking these proactive measures are to promote gender equality and workplace safety and to cultivate and retain effective female leadership in medical institutions and training programs.

We feel incredibly fortunate to be part of a specialty in which gender equality has long been considered and sought after. We also are proud to be members of the Association of Professors of Dermatology, which has addressed issues such as diversity and gender equality in a transparent and head-on manner and continues to do so. As a specialty, we hope we can support our trainees in their professional growth and help to cultivate sensitive physicians who will care for an increasingly diverse population and better support each other in their own career development.

The #MeToo movement that took hold in the wake of the Harvey Weinstein allegations in 2017 likely will be considered one of the major cultural touchpoints of the 2010s. Although activism within the entertainment industry initially drew attention to this movement, it is understood that virtually no workplace is immune to sexual misconduct. Many medical professionals acknowledge #MeToo as a catchy hashtag summarizing a problem that has long been recognized in the field of medicine but often has been inadequately addressed.¹ As dermatology residency program directors (PDs) at the University of Southern California (USC) Keck School of Medicine (Los Angeles, California), we have seen the considerable impact that recent high-profile allegations of sexual assault have had at our institution, leading us to take part in institutional and departmental initiatives and reflections that we believe have strengthened the culture within our residency program and positioned us to be proactive in addressing this critical issue.

Before we discuss the efforts to combat sexual misconduct and gender inequality at USC and within our dermatology department, it is worth reflecting on where we stand as a specialty with regard to gender representation. A recent JAMA Dermatology article reported that in 1970 only 10.8% of dermatology academic faculty were women but by 2018 that number had skyrocketed to 51.2%; however, in contrast to this overall increase, only 19.4% of dermatology department chairs in 2018 were women.² Although we have made large strides as a field, this discrepancy indicates that we still have a long way to go to achieve gender equality.

Although dermatology as a specialty is working toward gender equality, we believe it is crucial to consider this issue in the context of the entire field of medicine, particularly because academic physicians and trainees often interface with a myriad of specialties. It is well known that women in medicine are more likely to be victims of sexual harassment or assault in the workplace and that subsequent issues with imposter syndrome and/or depression are more prevalent in female physicians.^3,4 Gender inequality and sexism, among other factors, can make it difficult for women to obtain and maintain leadership positions and can negatively impact the culture of an academic institution in numerous downstream ways.

We also know that academic environments in medicine have a higher prevalence of gender equality issues than in private practice or in settings where medicine is practiced without trainees due to the hierarchical nature of training and the necessary differences in experience between trainees and faculty.³ Furthermore, because trainees form and solidify their professional identities during graduate medical education (GME) training, it is a prime time to emphasize the importance of gender equality and establish zero tolerance policies for workplace abuse and transgressions.⁵

The data and our personal experiences delineate a clear need for continued vigilance regarding gender equality issues both in dermatology as a specialty and in medicine in general. As PDs, we feel fortunate to have worked in conjunction with our GME committee and our dermatology department to solidify and create policies that work to promote a culture of gender equality. Herein, we will outline some of these efforts with the hope that other academic institutions may consider implementing these programs to protect members of their community from harassment, sexual violence, and gender discrimination.

Create a SAFE Committee

At the institutional level, our GME committee has created the SAFE (Safety, Fairness & Equity) committee under the leadership of Lawrence Opas, MD. The SAFE committee is headed by a female faculty physician and includes members of the medical community who have the influence to affect change and a commitment to protect vulnerable populations. Members include the Chief Medical Officer, the Designated Institutional Officer, the Director of Resident Wellness, and the Dean of the Keck School of Medicine at USC. The SAFE committee serves as a 24/7 reporting resource whereby trainees can report any issues relating to harassment in the workplace via a telephone hotline or online platform. Issues brought to this committee are immediately dealt with and reviewed at monthly GME meetings to keep institutional PDs up-to-date on issues pertaining to sexual harassment and assault within our workplace. The SAFE committee also has departmental resident liaisons who bring information to residents and help guide them to appropriate resources.

Emphasize Resident Wellness

Along with the development of robust reporting resources, our institution has continued to build upon a culture that places a strong emphasis on resident wellness. One of the most meaningful efforts over the last 5 years has included recruitment of a clinical psychologist, Tobi Fishel, PhD, to serve as our institution’s Director of Wellness. She is available to meet confidentially with our residents and helps to serve as a link between trainees and the GME committee.

Our dermatology department takes a tremendous amount of pride in its culture. We are fortunate to have David Peng, MD, MPH, Chair, and Stefani Takahashi, MD, Vice Chair of Education, working daily to create an environment that values teamwork, selflessness, and wellness. We have been continuously grateful for their leadership and guidance in addressing the allegations of sexual assault and harassment that arose at USC over the past several years. Our department has a zero tolerance policy for sexual harassment or harassment of any kind, and we have taken important steps to ensure and promote a safe environment for our trainees, many of which are focused on communication. We try to avoid assumptions and encourage both residents and faculty to explicitly state their experiences and opinions in general but also in relation to instances of potential misconduct.

Encourage Communication

When allegations of sexual misconduct in the workplace were made at our institution, we prioritized immediate in-person communication with our residents to reinforce our zero tolerance policy and to remind them that we are available should any similar issues arise in our department. It was of equal value to remind our trainees of potential resources, such as the SAFE committee, to whom they could bring their concerns if they were not comfortable communicating directly with us. Although we hoped that our trainees understood that we would not be tolerant of any form of harassment based on our past actions and communications, we felt that it was helpful to explicitly delineate this by laying out other avenues of support on a regular basis with them. By ensuring there is a space for a dialogue with others, if needed, our institution and department have provided an extra layer of security for our trainees. Multiple channels of support are crucial to ensure trainee safety.

Dr. Peng also created a workplace safety committee that includes several female faculty members. The committee regularly shares and highlights institutional and departmental resources as they pertain to gender equality and safety within the workplace and also has considerable faculty overlap with our departmental diversity committee. Together, these committees work toward the common goal of fostering an environment in which all members of our department feel comfortable voicing concerns, and we are best able to recruit and retain a diverse faculty.

As PDs, we work to reinforce departmental and institutional messages in our daily communication with residents. We have found that ensuring frequent and varied interactions—quarterly meetings, biannual evaluations, faculty-led didactics 2 half-days per week, and weekly clinical interactions—with our trainees can help to create a culture where they feel comfortable bringing up issues, be they routine clinical operations questions or issues relating to their professional identity. We hope it also has created the space for them to approach us with any issues pertaining to harassment should they ever arise, and we are grateful to know that even if this comfort does not exist, our institution and department have other resources for them.

Final Thoughts

Although some of the measures discussed here were reactionary, many predated the recent institutional concerns and allegations at USC. We hope and believe that the culture we foster within our department has helped our trainees feel safe and cared for during a time of institutional turbulence. We also believe that taking similar proactive measures may benefit the overall culture and foster the development of diverse physicians and leadership at other institutions. In conjunction with reworking legislation and implementing institutional safeguards, the long-term goals of taking these proactive measures are to promote gender equality and workplace safety and to cultivate and retain effective female leadership in medical institutions and training programs.

We feel incredibly fortunate to be part of a specialty in which gender equality has long been considered and sought after. We also are proud to be members of the Association of Professors of Dermatology, which has addressed issues such as diversity and gender equality in a transparent and head-on manner and continues to do so. As a specialty, we hope we can support our trainees in their professional growth and help to cultivate sensitive physicians who will care for an increasingly diverse population and better support each other in their own career development.

To the Editor:

We report an interesting clinical case of dermatomyositis (DM) that presented with an associated malignancy (small cell lung cancer). This patient also had an unusual clinical finding of predominantly unilateral, confluent, erythematous papules on the knee, a cutaneous sign that is seldom described in the DM literature. This case serves to reinforce the classic findings and associations of DM, in addition to the uncommon manifestation of predominantly unilateral papules on the knee.

A 68-year-old woman presented with several cutaneous manifestations including the classic findings of photo distributed erythema on the arms and face, a heliotrope rash, Gottron papules, and confluent pink papules on the left knee (Figure 1). The patient also had one of the more rare manifestations of DM, flagellate erythema on the back (Figure 2). She had a history of breast cancer and was found to have metastatic small cell lung cancer at the time of the DM diagnosis.

To the Editor:

We report an interesting clinical case of dermatomyositis (DM) that presented with an associated malignancy (small cell lung cancer). This patient also had an unusual clinical finding of predominantly unilateral, confluent, erythematous papules on the knee, a cutaneous sign that is seldom described in the DM literature. This case serves to reinforce the classic findings and associations of DM, in addition to the uncommon manifestation of predominantly unilateral papules on the knee.

A 68-year-old woman presented with several cutaneous manifestations including the classic findings of photo distributed erythema on the arms and face, a heliotrope rash, Gottron papules, and confluent pink papules on the left knee (Figure 1). The patient also had one of the more rare manifestations of DM, flagellate erythema on the back (Figure 2). She had a history of breast cancer and was found to have metastatic small cell lung cancer at the time of the DM diagnosis.

To the Editor:

We report an interesting clinical case of dermatomyositis (DM) that presented with an associated malignancy (small cell lung cancer). This patient also had an unusual clinical finding of predominantly unilateral, confluent, erythematous papules on the knee, a cutaneous sign that is seldom described in the DM literature. This case serves to reinforce the classic findings and associations of DM, in addition to the uncommon manifestation of predominantly unilateral papules on the knee.

A 68-year-old woman presented with several cutaneous manifestations including the classic findings of photo distributed erythema on the arms and face, a heliotrope rash, Gottron papules, and confluent pink papules on the left knee (Figure 1). The patient also had one of the more rare manifestations of DM, flagellate erythema on the back (Figure 2). She had a history of breast cancer and was found to have metastatic small cell lung cancer at the time of the DM diagnosis.

To the Editor:

Acrodermatitis enteropathica (AE) is an inherited defect in zinc absorption that leads to hypozincemia. Its clinical presentation can vary based on serum zinc level and ranges from periorificial erosive dermatitis to psoriasiform dermatitis.¹ Recognition of the cutaneous manifestations of zinc deficiency can lead to early intervention with zinc supplementation and prevention of long-term morbidity and even mortality. In our case, the coexistence of a bullous acral dermatosis with the additional feature of extensor digital dermatitis with fissuring suggests a diagnosis of AE and can alert the astute clinician to the need for testing of serum zinc levels and/or treatment with zinc supplementation. Causes of acquired zinc deficiency that have been reported in the literature include eating disorders such as anorexia nervosa and bulimia nervosa, Crohn disease, food allergy, intestinal parasitic infestations, and an inborn error of metabolism known as nonketotic hyperglycemia (Table).^2-4

RELATED ARTICLE: Acquired Acrodermatitis Enteropathica Secondary to Alcoholism

A 42-year-old woman with a medical history of rheumatoid arthritis and short bowel syndrome due to multiple small bowel obstructions with subsequent bowel resections who was on chronic total parenteral nutrition (TPN) presented with bullae on the hands, shins, and feet. The patient initially noticed small erythematous macules on the hands and feet months prior to presentation. Three weeks prior to presentation, bullae started to form on the hands, mostly between the web spaces; dorsal aspects of the feet; and anterior aspects of the shins. The patient denied any oral ulcers. One day prior to presentation the patient was seen at an outside hospital and was started on prednisone 5 mg daily, oral clindamycin, mupirocin ointment, and nystatin-triamcinolone cream. These medications failed to improve her condition. On review of systems, the patient denied any fever, chills, eye pain, or dysuria.

Upon initial presentation the patient appeared weak and fatigued, though vital signs were normal. Physical examination revealed multiple flaccid bullae in the web spaces of the hands and shallow erosions with hemorrhagic crusts on the bilateral wrists. She also had violaceous patches in the extensor creases of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, which were strikingly symmetric (Figure 1). Prominent flaccid bullae and shallow erosions with hemorrhagic crusts also were present on the bilateral shins and dorsal aspects of the feet (Figure 2). No oral ulcers were present. A punch biopsy from the dorsal aspect of the left foot revealed psoriasiform hyperplasia of the epidermis with prominent ballooning degeneration and hyperkeratosis/parakeratosis (Figure 3); a periodic acid–Schiff stain was negative for fungal organisms.

Given the biopsy results and clinical presentation, a nutritional deficiency was suspected and serum levels of zinc, vitamin B₁, vitamin B₂, and vitamin B₃ were assessed. Vitamins B₁, B₂, and B₃ all were within reference range, but the patient’s serum zinc level was found to be low at 11 μg/mL (reference range, 55–150 μg/mL). The alkaline phosphatase level also was measured to be low at 22 U/L (reference range, 31–103 U/L). Additionally, a hepatitis panel was drawn and glucagon levels were checked, which were found to be within reference range. These findings were consistent with a diagnosis of acquired AE. Prednisone and clindamycin were stopped and the patient was started on zinc supplementation in her TPN therapy. Mupirocin ointment was continued on the existing bullae. Upon discharge 10 days later, there were no new bullae and the existing bullae had sloughed off, revealing healthy skin underneath.

Zinc is an essential trace element and can be found in high concentration in foods such as shellfish, green vegetables, legumes, nuts, and whole grains.⁶ The majority of zinc is absorbed in the jejunum; as such, many cases of acquired zinc deficiency leading to AE are dueto disorders that affect the small intestine.² Conditions that may lead to poor gastrointestinal zinc absorption include alcoholism, eating disorders, TPN, burns, surgery, and malignancies.^2,7

Diagnosis typically is made based on characteristic clinical features, biopsy results, and a measurement of the serum zinc concentration. Although a low serum zinc level supports the diagnosis, serum zinc concentration is not a reliable indicator of body zinc stores and a normal serum zinc concentration does not rule out AE. The gold standard for diagnosis is the resolution of lesions after zinc supplementation.¹ Notably, because the production of alkaline phosphatase is dependent on zinc, levels of this enzyme also may be low in cases of AE,⁶ as in our patient.

The clinical manifestations of AE can vary greatly; patients may initially present with eczematous pink scaly plaques, which may subsequently become vesicular, bullous, pustular, or desquamative. The lesions may develop over the arms and legs as well as the anogenital and periorificial areas.⁵ Other notable manifestations that may present early in the course of AE include angular cheilitis followed by paronychia. In patients who are not promptly treated, long-term zinc deficiency may lead to growth delay, mental slowing, poor wound healing, anemia, and anorexia.⁵ Of note, deficiencies of branched-chain amino acids and essential fatty acids may appear clinically similar to AE.²

Zinc replacement is the treatment of choice for patients with AE due to dietary deficiency, and replacement therapy should begin with 0.5 to 1 mg/kg daily of elemental zinc.⁵ Response to acquired AE with zinc supplementation often is rapid. Lesions tend to resolve within days to weeks depending on the degree of deficiency.²

Although AE is an uncommon dermatosis in the United States, it is an important diagnosis to make because its clinical features are fairly specific and early zinc supplementation allows for full resolution of the disease without permanent sequelae. The diagnosis of AE should be strongly considered when features of an acral bullous dermatosis are combined with a fissured dermatitis of extensor joints of the hands or elbows. It is particularly important to recognize that alcoholics, burn victims, postsurgical patients, and those with malignancies and eating disorders are at an increased risk for developing this nutritional deficiency.

To the Editor:

Acrodermatitis enteropathica (AE) is an inherited defect in zinc absorption that leads to hypozincemia. Its clinical presentation can vary based on serum zinc level and ranges from periorificial erosive dermatitis to psoriasiform dermatitis.¹ Recognition of the cutaneous manifestations of zinc deficiency can lead to early intervention with zinc supplementation and prevention of long-term morbidity and even mortality. In our case, the coexistence of a bullous acral dermatosis with the additional feature of extensor digital dermatitis with fissuring suggests a diagnosis of AE and can alert the astute clinician to the need for testing of serum zinc levels and/or treatment with zinc supplementation. Causes of acquired zinc deficiency that have been reported in the literature include eating disorders such as anorexia nervosa and bulimia nervosa, Crohn disease, food allergy, intestinal parasitic infestations, and an inborn error of metabolism known as nonketotic hyperglycemia (Table).^2-4

RELATED ARTICLE: Acquired Acrodermatitis Enteropathica Secondary to Alcoholism

A 42-year-old woman with a medical history of rheumatoid arthritis and short bowel syndrome due to multiple small bowel obstructions with subsequent bowel resections who was on chronic total parenteral nutrition (TPN) presented with bullae on the hands, shins, and feet. The patient initially noticed small erythematous macules on the hands and feet months prior to presentation. Three weeks prior to presentation, bullae started to form on the hands, mostly between the web spaces; dorsal aspects of the feet; and anterior aspects of the shins. The patient denied any oral ulcers. One day prior to presentation the patient was seen at an outside hospital and was started on prednisone 5 mg daily, oral clindamycin, mupirocin ointment, and nystatin-triamcinolone cream. These medications failed to improve her condition. On review of systems, the patient denied any fever, chills, eye pain, or dysuria.

Upon initial presentation the patient appeared weak and fatigued, though vital signs were normal. Physical examination revealed multiple flaccid bullae in the web spaces of the hands and shallow erosions with hemorrhagic crusts on the bilateral wrists. She also had violaceous patches in the extensor creases of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, which were strikingly symmetric (Figure 1). Prominent flaccid bullae and shallow erosions with hemorrhagic crusts also were present on the bilateral shins and dorsal aspects of the feet (Figure 2). No oral ulcers were present. A punch biopsy from the dorsal aspect of the left foot revealed psoriasiform hyperplasia of the epidermis with prominent ballooning degeneration and hyperkeratosis/parakeratosis (Figure 3); a periodic acid–Schiff stain was negative for fungal organisms.

Given the biopsy results and clinical presentation, a nutritional deficiency was suspected and serum levels of zinc, vitamin B₁, vitamin B₂, and vitamin B₃ were assessed. Vitamins B₁, B₂, and B₃ all were within reference range, but the patient’s serum zinc level was found to be low at 11 μg/mL (reference range, 55–150 μg/mL). The alkaline phosphatase level also was measured to be low at 22 U/L (reference range, 31–103 U/L). Additionally, a hepatitis panel was drawn and glucagon levels were checked, which were found to be within reference range. These findings were consistent with a diagnosis of acquired AE. Prednisone and clindamycin were stopped and the patient was started on zinc supplementation in her TPN therapy. Mupirocin ointment was continued on the existing bullae. Upon discharge 10 days later, there were no new bullae and the existing bullae had sloughed off, revealing healthy skin underneath.

Zinc is an essential trace element and can be found in high concentration in foods such as shellfish, green vegetables, legumes, nuts, and whole grains.⁶ The majority of zinc is absorbed in the jejunum; as such, many cases of acquired zinc deficiency leading to AE are dueto disorders that affect the small intestine.² Conditions that may lead to poor gastrointestinal zinc absorption include alcoholism, eating disorders, TPN, burns, surgery, and malignancies.^2,7

Diagnosis typically is made based on characteristic clinical features, biopsy results, and a measurement of the serum zinc concentration. Although a low serum zinc level supports the diagnosis, serum zinc concentration is not a reliable indicator of body zinc stores and a normal serum zinc concentration does not rule out AE. The gold standard for diagnosis is the resolution of lesions after zinc supplementation.¹ Notably, because the production of alkaline phosphatase is dependent on zinc, levels of this enzyme also may be low in cases of AE,⁶ as in our patient.

The clinical manifestations of AE can vary greatly; patients may initially present with eczematous pink scaly plaques, which may subsequently become vesicular, bullous, pustular, or desquamative. The lesions may develop over the arms and legs as well as the anogenital and periorificial areas.⁵ Other notable manifestations that may present early in the course of AE include angular cheilitis followed by paronychia. In patients who are not promptly treated, long-term zinc deficiency may lead to growth delay, mental slowing, poor wound healing, anemia, and anorexia.⁵ Of note, deficiencies of branched-chain amino acids and essential fatty acids may appear clinically similar to AE.²

Zinc replacement is the treatment of choice for patients with AE due to dietary deficiency, and replacement therapy should begin with 0.5 to 1 mg/kg daily of elemental zinc.⁵ Response to acquired AE with zinc supplementation often is rapid. Lesions tend to resolve within days to weeks depending on the degree of deficiency.²

Although AE is an uncommon dermatosis in the United States, it is an important diagnosis to make because its clinical features are fairly specific and early zinc supplementation allows for full resolution of the disease without permanent sequelae. The diagnosis of AE should be strongly considered when features of an acral bullous dermatosis are combined with a fissured dermatitis of extensor joints of the hands or elbows. It is particularly important to recognize that alcoholics, burn victims, postsurgical patients, and those with malignancies and eating disorders are at an increased risk for developing this nutritional deficiency.

To the Editor:

Acrodermatitis enteropathica (AE) is an inherited defect in zinc absorption that leads to hypozincemia. Its clinical presentation can vary based on serum zinc level and ranges from periorificial erosive dermatitis to psoriasiform dermatitis.¹ Recognition of the cutaneous manifestations of zinc deficiency can lead to early intervention with zinc supplementation and prevention of long-term morbidity and even mortality. In our case, the coexistence of a bullous acral dermatosis with the additional feature of extensor digital dermatitis with fissuring suggests a diagnosis of AE and can alert the astute clinician to the need for testing of serum zinc levels and/or treatment with zinc supplementation. Causes of acquired zinc deficiency that have been reported in the literature include eating disorders such as anorexia nervosa and bulimia nervosa, Crohn disease, food allergy, intestinal parasitic infestations, and an inborn error of metabolism known as nonketotic hyperglycemia (Table).^2-4

RELATED ARTICLE: Acquired Acrodermatitis Enteropathica Secondary to Alcoholism

A 42-year-old woman with a medical history of rheumatoid arthritis and short bowel syndrome due to multiple small bowel obstructions with subsequent bowel resections who was on chronic total parenteral nutrition (TPN) presented with bullae on the hands, shins, and feet. The patient initially noticed small erythematous macules on the hands and feet months prior to presentation. Three weeks prior to presentation, bullae started to form on the hands, mostly between the web spaces; dorsal aspects of the feet; and anterior aspects of the shins. The patient denied any oral ulcers. One day prior to presentation the patient was seen at an outside hospital and was started on prednisone 5 mg daily, oral clindamycin, mupirocin ointment, and nystatin-triamcinolone cream. These medications failed to improve her condition. On review of systems, the patient denied any fever, chills, eye pain, or dysuria.

Upon initial presentation the patient appeared weak and fatigued, though vital signs were normal. Physical examination revealed multiple flaccid bullae in the web spaces of the hands and shallow erosions with hemorrhagic crusts on the bilateral wrists. She also had violaceous patches in the extensor creases of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, which were strikingly symmetric (Figure 1). Prominent flaccid bullae and shallow erosions with hemorrhagic crusts also were present on the bilateral shins and dorsal aspects of the feet (Figure 2). No oral ulcers were present. A punch biopsy from the dorsal aspect of the left foot revealed psoriasiform hyperplasia of the epidermis with prominent ballooning degeneration and hyperkeratosis/parakeratosis (Figure 3); a periodic acid–Schiff stain was negative for fungal organisms.

Given the biopsy results and clinical presentation, a nutritional deficiency was suspected and serum levels of zinc, vitamin B₁, vitamin B₂, and vitamin B₃ were assessed. Vitamins B₁, B₂, and B₃ all were within reference range, but the patient’s serum zinc level was found to be low at 11 μg/mL (reference range, 55–150 μg/mL). The alkaline phosphatase level also was measured to be low at 22 U/L (reference range, 31–103 U/L). Additionally, a hepatitis panel was drawn and glucagon levels were checked, which were found to be within reference range. These findings were consistent with a diagnosis of acquired AE. Prednisone and clindamycin were stopped and the patient was started on zinc supplementation in her TPN therapy. Mupirocin ointment was continued on the existing bullae. Upon discharge 10 days later, there were no new bullae and the existing bullae had sloughed off, revealing healthy skin underneath.

Zinc is an essential trace element and can be found in high concentration in foods such as shellfish, green vegetables, legumes, nuts, and whole grains.⁶ The majority of zinc is absorbed in the jejunum; as such, many cases of acquired zinc deficiency leading to AE are dueto disorders that affect the small intestine.² Conditions that may lead to poor gastrointestinal zinc absorption include alcoholism, eating disorders, TPN, burns, surgery, and malignancies.^2,7

Diagnosis typically is made based on characteristic clinical features, biopsy results, and a measurement of the serum zinc concentration. Although a low serum zinc level supports the diagnosis, serum zinc concentration is not a reliable indicator of body zinc stores and a normal serum zinc concentration does not rule out AE. The gold standard for diagnosis is the resolution of lesions after zinc supplementation.¹ Notably, because the production of alkaline phosphatase is dependent on zinc, levels of this enzyme also may be low in cases of AE,⁶ as in our patient.

The clinical manifestations of AE can vary greatly; patients may initially present with eczematous pink scaly plaques, which may subsequently become vesicular, bullous, pustular, or desquamative. The lesions may develop over the arms and legs as well as the anogenital and periorificial areas.⁵ Other notable manifestations that may present early in the course of AE include angular cheilitis followed by paronychia. In patients who are not promptly treated, long-term zinc deficiency may lead to growth delay, mental slowing, poor wound healing, anemia, and anorexia.⁵ Of note, deficiencies of branched-chain amino acids and essential fatty acids may appear clinically similar to AE.²

Zinc replacement is the treatment of choice for patients with AE due to dietary deficiency, and replacement therapy should begin with 0.5 to 1 mg/kg daily of elemental zinc.⁵ Response to acquired AE with zinc supplementation often is rapid. Lesions tend to resolve within days to weeks depending on the degree of deficiency.²

Although AE is an uncommon dermatosis in the United States, it is an important diagnosis to make because its clinical features are fairly specific and early zinc supplementation allows for full resolution of the disease without permanent sequelae. The diagnosis of AE should be strongly considered when features of an acral bullous dermatosis are combined with a fissured dermatitis of extensor joints of the hands or elbows. It is particularly important to recognize that alcoholics, burn victims, postsurgical patients, and those with malignancies and eating disorders are at an increased risk for developing this nutritional deficiency.