MDedge Dermatology

Opzelura FDA Approved for Atopic Dermatitis Incyte

Corporation announces US Food and Drug Administration (FDA) approval of Opzelura (ruxolitinib) cream 1.5% for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis (AD) in nonimmunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Opzelura is formulated with ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, to target key cytokine signals believed to contribute to itch and inflammation. For more information, visit www.opzelurahcp.com/.

Twyneo FDA Approved for Acne Vulgaris

Sol-Gel Technologies, Ltd, announces US Food and Drug Administration (FDA) approval of Twyneo (tretinoin 0.1% /benzoyl peroxide 3%) cream for the treatment of acne vulgaris in adult and pediatric patients 9 years and older. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. The formulation of Twyneo uses silica (silicon dioxide) core shell structures to separately microencapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the 2 active ingredients in the cream. For more information, visit www.sol-gel.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Opzelura FDA Approved for Atopic Dermatitis Incyte

Corporation announces US Food and Drug Administration (FDA) approval of Opzelura (ruxolitinib) cream 1.5% for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis (AD) in nonimmunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Opzelura is formulated with ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, to target key cytokine signals believed to contribute to itch and inflammation. For more information, visit www.opzelurahcp.com/.

Twyneo FDA Approved for Acne Vulgaris

Sol-Gel Technologies, Ltd, announces US Food and Drug Administration (FDA) approval of Twyneo (tretinoin 0.1% /benzoyl peroxide 3%) cream for the treatment of acne vulgaris in adult and pediatric patients 9 years and older. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. The formulation of Twyneo uses silica (silicon dioxide) core shell structures to separately microencapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the 2 active ingredients in the cream. For more information, visit www.sol-gel.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Opzelura FDA Approved for Atopic Dermatitis Incyte

Corporation announces US Food and Drug Administration (FDA) approval of Opzelura (ruxolitinib) cream 1.5% for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis (AD) in nonimmunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Opzelura is formulated with ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, to target key cytokine signals believed to contribute to itch and inflammation. For more information, visit www.opzelurahcp.com/.

Twyneo FDA Approved for Acne Vulgaris

Sol-Gel Technologies, Ltd, announces US Food and Drug Administration (FDA) approval of Twyneo (tretinoin 0.1% /benzoyl peroxide 3%) cream for the treatment of acne vulgaris in adult and pediatric patients 9 years and older. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. The formulation of Twyneo uses silica (silicon dioxide) core shell structures to separately microencapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the 2 active ingredients in the cream. For more information, visit www.sol-gel.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

The COVID-19 pandemic has markedly changed the dermatology residency application process. As medical students head into this application cycle, the impacts of systemic racism and deeply rooted structural barriers continue to be exacerbated for students who identify as an underrepresented minority (URM) in medicine—historically defined as those who self-identify as Hispanic or Latinx; Black or African American; American Indian or Alaska Native; or Native Hawaiian or Pacific Islander. The Association of American Medical Colleges (AAMC) defines URMs as racial and ethnic populations that are underrepresented in medicine relative to their numbers in the general population.¹ Although these groups account for approximately 34% of the population of the United States, they constitute only 11% of the country’s physician workforce.^2,3

Of the total physician workforce in the United States, Black and African American physicians account for 5% of practicing physicians; Hispanic physicians, 5.8%; American Indian and Alaska Native physicians, 0.3%; and Native Hawaiian and Pacific Islander physicians, 0.1%.² In competitive medical specialties, the disproportionality of these numbers compared to our current demographics in the United States as shown above is even more staggering. In 2018, for example, 10% of practicing dermatologists identified as female URM physicians; 6%, as male URM physicians.² In this article, we discuss some of the challenges and considerations for URM students applying to dermatology residency in the era of the COVID-19 pandemic.

Barriers for URM Students in Dermatology

Multiple studies have attempted to identify some of the barriers faced by URM students in medicine that might explain the lack of diversity in competitive specialties. Vasquez and colleagues⁴ identified 4 major factors that play a role in dermatology: lack of equitable resources, lack of support, financial limitations, and the lack of group identity. More than half of URM students surveyed (1) identified lack of support as a barrier and (2) reported having been encouraged to seek a specialty more reflective of their community.⁴

Soliman et al⁵ reported that URM barriers in dermatology extend to include lack of diversity in the field, socioeconomic factors, lack of mentorship, and a negative perception of minority students by residency programs. Dermatology is the second least diverse specialty in medicine after orthopedic surgery, which, in and of itself, might further discourage URM students from applying to dermatology.⁵

With the minimal exposure that URM students have to the field of dermatology, the lack of pipeline programs, and reports that URMs often are encouraged to pursue primary care, the current diversity deficiency in dermatology comes as no surprise. In addition, the substantial disadvantage for URM students is perpetuated by the traditional highly selective process that favors grades, board scores, and honor society status over holistic assessment of the individual student and their unique experiences and potential for contribution.

Looking Beyond Test Scores

The US Medical Licensing Examination (USMLE) traditionally has been used to select dermatology residency applicants, with high cutoff scores often excluding outstanding URM students. Research has suggested that the use of USMLE examination test scores for residency recruitment lacks validity because it has poor predictability of residency performance.⁶ Although the USMLE Step 1 examination is transitioning to pass/fail scoring, applicants for the next cycle will still have a 3-digit numerical score.

We strongly recommend that dermatology programs transition from emphasizing scores of residency candidates to reviewing each candidate holistically. The AAMC defines “holistic review” as a “flexible, individualized way of assessing an applicant’s capabilities, by which balanced consideration is given to experiences, attributes, competencies, and academic or scholarly metrics and, when considered in combination, how the individual might contribute value to the institution’s mission.”⁷ Furthermore, we recommend that dermatology residency programs have multiple faculty members review each application, including a representative of the diversity, inclusion, and equity committee.

In the COVID-19 era, dermatology externship opportunities that would have allowed URM students to work directly with potential residency programs, showcase their abilities, and network have been limited. Virtual residency interviews could make it more challenging to evaluate candidates, especially URM students from less prestigious programs or unusual socioeconomic backgrounds, or with lower board scores. In addition, virtual interviews can more easily become one-dimensional, depriving URM students of the opportunity to gauge their personal fit in a specific dermatology residency program and its community. Questions and concerns of URM students might include: Will I be appropriately supported and mentored? Will my cultural preferences, religion, sexual preference, hairstyle, and beliefs be accepted? Can I advocate for minorities and support antiracism and diversity and inclusion initiatives? To that end, we recommend that dermatology programs continue to host virtual meet-and-greet events for potential students to meet faculty and learn more about the program. In addition, programs should consider having current residents interact virtually with candidates to allow students to better understand the culture of the department and residents’ experiences as trainees in such an environment. For URM students, this is highly important because diversity, inclusion, and antiracism policies and initiatives might not be explicitly available on the institution’s website or residency information page.

Organizations Championing Diversity

Recently, multiple dermatology societies and organizations have been emphasizing the need for diversity and inclusion as well as promoting holistic application review. The American Academy of Dermatology pioneered the Diversity Champion Workshop in 2019 and continues to offer the Diversity Mentorship program, connecting URM students to mentors nationally. The Skin of Color Society offers yearly grants and awards to medical students to develop mentorship and research, and recently hosted webinars to guide medical students and residency programs on diversity and inclusion, residency application and review, and COVID-19 virtual interviews. Other national societies, such as the Student National Medical Association and Latino Medical Student Association, have been promoting workshops and interview mentoring for URM students, including dermatology-specific events. Although it is estimated that more than 90% of medical schools in the United States already perform holistic application review and that such review has been adopted by many dermatology programs nationwide, data regarding dermatology residency programs’ implementation of holistic application review are lacking.⁸

In addition, we encourage continuation of the proposed coordinated interview invite release from the Association of Professors of Dermatology, which was implemented in the 2020-2021 cycle. In light of the recent AAMC letter⁹ on the maldistribution of interview invitations to highest-tier applicants, coordination of interview release dates and other similar initiatives to prevent programs from offering more invites than their available slots and improve transparency about interview days are needed. Furthermore, continuing to offer optional virtual interviews for applicants in future cycles could make the process less cost-prohibitive for many URM students.^4,5

Final Thoughts

Dermatology residency programs must intentionally guard against falling back to traditional standards of assessment as the only means of student evaluation, especially in this virtual era. It is our responsibility to remove artificial barriers that continue to stall progress in diversity, inclusion, equity, and belonging in dermatology.

The COVID-19 pandemic has markedly changed the dermatology residency application process. As medical students head into this application cycle, the impacts of systemic racism and deeply rooted structural barriers continue to be exacerbated for students who identify as an underrepresented minority (URM) in medicine—historically defined as those who self-identify as Hispanic or Latinx; Black or African American; American Indian or Alaska Native; or Native Hawaiian or Pacific Islander. The Association of American Medical Colleges (AAMC) defines URMs as racial and ethnic populations that are underrepresented in medicine relative to their numbers in the general population.¹ Although these groups account for approximately 34% of the population of the United States, they constitute only 11% of the country’s physician workforce.^2,3

Of the total physician workforce in the United States, Black and African American physicians account for 5% of practicing physicians; Hispanic physicians, 5.8%; American Indian and Alaska Native physicians, 0.3%; and Native Hawaiian and Pacific Islander physicians, 0.1%.² In competitive medical specialties, the disproportionality of these numbers compared to our current demographics in the United States as shown above is even more staggering. In 2018, for example, 10% of practicing dermatologists identified as female URM physicians; 6%, as male URM physicians.² In this article, we discuss some of the challenges and considerations for URM students applying to dermatology residency in the era of the COVID-19 pandemic.

Barriers for URM Students in Dermatology

Multiple studies have attempted to identify some of the barriers faced by URM students in medicine that might explain the lack of diversity in competitive specialties. Vasquez and colleagues⁴ identified 4 major factors that play a role in dermatology: lack of equitable resources, lack of support, financial limitations, and the lack of group identity. More than half of URM students surveyed (1) identified lack of support as a barrier and (2) reported having been encouraged to seek a specialty more reflective of their community.⁴

Soliman et al⁵ reported that URM barriers in dermatology extend to include lack of diversity in the field, socioeconomic factors, lack of mentorship, and a negative perception of minority students by residency programs. Dermatology is the second least diverse specialty in medicine after orthopedic surgery, which, in and of itself, might further discourage URM students from applying to dermatology.⁵

With the minimal exposure that URM students have to the field of dermatology, the lack of pipeline programs, and reports that URMs often are encouraged to pursue primary care, the current diversity deficiency in dermatology comes as no surprise. In addition, the substantial disadvantage for URM students is perpetuated by the traditional highly selective process that favors grades, board scores, and honor society status over holistic assessment of the individual student and their unique experiences and potential for contribution.

Looking Beyond Test Scores

The US Medical Licensing Examination (USMLE) traditionally has been used to select dermatology residency applicants, with high cutoff scores often excluding outstanding URM students. Research has suggested that the use of USMLE examination test scores for residency recruitment lacks validity because it has poor predictability of residency performance.⁶ Although the USMLE Step 1 examination is transitioning to pass/fail scoring, applicants for the next cycle will still have a 3-digit numerical score.

We strongly recommend that dermatology programs transition from emphasizing scores of residency candidates to reviewing each candidate holistically. The AAMC defines “holistic review” as a “flexible, individualized way of assessing an applicant’s capabilities, by which balanced consideration is given to experiences, attributes, competencies, and academic or scholarly metrics and, when considered in combination, how the individual might contribute value to the institution’s mission.”⁷ Furthermore, we recommend that dermatology residency programs have multiple faculty members review each application, including a representative of the diversity, inclusion, and equity committee.

In the COVID-19 era, dermatology externship opportunities that would have allowed URM students to work directly with potential residency programs, showcase their abilities, and network have been limited. Virtual residency interviews could make it more challenging to evaluate candidates, especially URM students from less prestigious programs or unusual socioeconomic backgrounds, or with lower board scores. In addition, virtual interviews can more easily become one-dimensional, depriving URM students of the opportunity to gauge their personal fit in a specific dermatology residency program and its community. Questions and concerns of URM students might include: Will I be appropriately supported and mentored? Will my cultural preferences, religion, sexual preference, hairstyle, and beliefs be accepted? Can I advocate for minorities and support antiracism and diversity and inclusion initiatives? To that end, we recommend that dermatology programs continue to host virtual meet-and-greet events for potential students to meet faculty and learn more about the program. In addition, programs should consider having current residents interact virtually with candidates to allow students to better understand the culture of the department and residents’ experiences as trainees in such an environment. For URM students, this is highly important because diversity, inclusion, and antiracism policies and initiatives might not be explicitly available on the institution’s website or residency information page.

Organizations Championing Diversity

Recently, multiple dermatology societies and organizations have been emphasizing the need for diversity and inclusion as well as promoting holistic application review. The American Academy of Dermatology pioneered the Diversity Champion Workshop in 2019 and continues to offer the Diversity Mentorship program, connecting URM students to mentors nationally. The Skin of Color Society offers yearly grants and awards to medical students to develop mentorship and research, and recently hosted webinars to guide medical students and residency programs on diversity and inclusion, residency application and review, and COVID-19 virtual interviews. Other national societies, such as the Student National Medical Association and Latino Medical Student Association, have been promoting workshops and interview mentoring for URM students, including dermatology-specific events. Although it is estimated that more than 90% of medical schools in the United States already perform holistic application review and that such review has been adopted by many dermatology programs nationwide, data regarding dermatology residency programs’ implementation of holistic application review are lacking.⁸

In addition, we encourage continuation of the proposed coordinated interview invite release from the Association of Professors of Dermatology, which was implemented in the 2020-2021 cycle. In light of the recent AAMC letter⁹ on the maldistribution of interview invitations to highest-tier applicants, coordination of interview release dates and other similar initiatives to prevent programs from offering more invites than their available slots and improve transparency about interview days are needed. Furthermore, continuing to offer optional virtual interviews for applicants in future cycles could make the process less cost-prohibitive for many URM students.^4,5

Final Thoughts

Dermatology residency programs must intentionally guard against falling back to traditional standards of assessment as the only means of student evaluation, especially in this virtual era. It is our responsibility to remove artificial barriers that continue to stall progress in diversity, inclusion, equity, and belonging in dermatology.

The COVID-19 pandemic has markedly changed the dermatology residency application process. As medical students head into this application cycle, the impacts of systemic racism and deeply rooted structural barriers continue to be exacerbated for students who identify as an underrepresented minority (URM) in medicine—historically defined as those who self-identify as Hispanic or Latinx; Black or African American; American Indian or Alaska Native; or Native Hawaiian or Pacific Islander. The Association of American Medical Colleges (AAMC) defines URMs as racial and ethnic populations that are underrepresented in medicine relative to their numbers in the general population.¹ Although these groups account for approximately 34% of the population of the United States, they constitute only 11% of the country’s physician workforce.^2,3

Of the total physician workforce in the United States, Black and African American physicians account for 5% of practicing physicians; Hispanic physicians, 5.8%; American Indian and Alaska Native physicians, 0.3%; and Native Hawaiian and Pacific Islander physicians, 0.1%.² In competitive medical specialties, the disproportionality of these numbers compared to our current demographics in the United States as shown above is even more staggering. In 2018, for example, 10% of practicing dermatologists identified as female URM physicians; 6%, as male URM physicians.² In this article, we discuss some of the challenges and considerations for URM students applying to dermatology residency in the era of the COVID-19 pandemic.

Barriers for URM Students in Dermatology

Multiple studies have attempted to identify some of the barriers faced by URM students in medicine that might explain the lack of diversity in competitive specialties. Vasquez and colleagues⁴ identified 4 major factors that play a role in dermatology: lack of equitable resources, lack of support, financial limitations, and the lack of group identity. More than half of URM students surveyed (1) identified lack of support as a barrier and (2) reported having been encouraged to seek a specialty more reflective of their community.⁴

Soliman et al⁵ reported that URM barriers in dermatology extend to include lack of diversity in the field, socioeconomic factors, lack of mentorship, and a negative perception of minority students by residency programs. Dermatology is the second least diverse specialty in medicine after orthopedic surgery, which, in and of itself, might further discourage URM students from applying to dermatology.⁵

With the minimal exposure that URM students have to the field of dermatology, the lack of pipeline programs, and reports that URMs often are encouraged to pursue primary care, the current diversity deficiency in dermatology comes as no surprise. In addition, the substantial disadvantage for URM students is perpetuated by the traditional highly selective process that favors grades, board scores, and honor society status over holistic assessment of the individual student and their unique experiences and potential for contribution.

Looking Beyond Test Scores

The US Medical Licensing Examination (USMLE) traditionally has been used to select dermatology residency applicants, with high cutoff scores often excluding outstanding URM students. Research has suggested that the use of USMLE examination test scores for residency recruitment lacks validity because it has poor predictability of residency performance.⁶ Although the USMLE Step 1 examination is transitioning to pass/fail scoring, applicants for the next cycle will still have a 3-digit numerical score.

We strongly recommend that dermatology programs transition from emphasizing scores of residency candidates to reviewing each candidate holistically. The AAMC defines “holistic review” as a “flexible, individualized way of assessing an applicant’s capabilities, by which balanced consideration is given to experiences, attributes, competencies, and academic or scholarly metrics and, when considered in combination, how the individual might contribute value to the institution’s mission.”⁷ Furthermore, we recommend that dermatology residency programs have multiple faculty members review each application, including a representative of the diversity, inclusion, and equity committee.

In the COVID-19 era, dermatology externship opportunities that would have allowed URM students to work directly with potential residency programs, showcase their abilities, and network have been limited. Virtual residency interviews could make it more challenging to evaluate candidates, especially URM students from less prestigious programs or unusual socioeconomic backgrounds, or with lower board scores. In addition, virtual interviews can more easily become one-dimensional, depriving URM students of the opportunity to gauge their personal fit in a specific dermatology residency program and its community. Questions and concerns of URM students might include: Will I be appropriately supported and mentored? Will my cultural preferences, religion, sexual preference, hairstyle, and beliefs be accepted? Can I advocate for minorities and support antiracism and diversity and inclusion initiatives? To that end, we recommend that dermatology programs continue to host virtual meet-and-greet events for potential students to meet faculty and learn more about the program. In addition, programs should consider having current residents interact virtually with candidates to allow students to better understand the culture of the department and residents’ experiences as trainees in such an environment. For URM students, this is highly important because diversity, inclusion, and antiracism policies and initiatives might not be explicitly available on the institution’s website or residency information page.

Organizations Championing Diversity

Recently, multiple dermatology societies and organizations have been emphasizing the need for diversity and inclusion as well as promoting holistic application review. The American Academy of Dermatology pioneered the Diversity Champion Workshop in 2019 and continues to offer the Diversity Mentorship program, connecting URM students to mentors nationally. The Skin of Color Society offers yearly grants and awards to medical students to develop mentorship and research, and recently hosted webinars to guide medical students and residency programs on diversity and inclusion, residency application and review, and COVID-19 virtual interviews. Other national societies, such as the Student National Medical Association and Latino Medical Student Association, have been promoting workshops and interview mentoring for URM students, including dermatology-specific events. Although it is estimated that more than 90% of medical schools in the United States already perform holistic application review and that such review has been adopted by many dermatology programs nationwide, data regarding dermatology residency programs’ implementation of holistic application review are lacking.⁸

In addition, we encourage continuation of the proposed coordinated interview invite release from the Association of Professors of Dermatology, which was implemented in the 2020-2021 cycle. In light of the recent AAMC letter⁹ on the maldistribution of interview invitations to highest-tier applicants, coordination of interview release dates and other similar initiatives to prevent programs from offering more invites than their available slots and improve transparency about interview days are needed. Furthermore, continuing to offer optional virtual interviews for applicants in future cycles could make the process less cost-prohibitive for many URM students.^4,5

Final Thoughts

Dermatology residency programs must intentionally guard against falling back to traditional standards of assessment as the only means of student evaluation, especially in this virtual era. It is our responsibility to remove artificial barriers that continue to stall progress in diversity, inclusion, equity, and belonging in dermatology.

To the Editor:

The tumor necrosis factor α inhibitor adalimumab is the only US Food and Drug Administration–approved treatment of hidradenitis suppurativa (HS). Although 50.6% of patients fulfilled Hidradenitis Suppurativa Clinical Response criteria with adalimumab at 12 weeks, many responders were not satisfied with their disease control, and secondary loss of Hidradenitis Suppurativa Clinical Response fulfillment occurred in 15.9% of patients within approximately 3 years.¹ Without other US Food and Drug Administration–approved HS treatments, some dermatologists have combined adalimumab with methotrexate (MTX) and/or mycophenolate mofetil (MMF) to attempt to increase the duration of satisfactory disease control while on adalimumab. Combining tumor necrosis factor α inhibitors with oral immunosuppressants is a well-established approach in psoriasis, psoriatic arthritis, and inflammatory bowel disease; however, to the best of our knowledge, this approach has not been studied for HS.^2,3

To assess whether there is a role for combining adalimumab with MTX and/or MMF in the treatment of HS, we performed a single-institution retrospective chart review at the University of Connecticut Department of Dermatology to determine whether patients receiving combination therapy stayed on adalimumab longer than those who received adalimumab monotherapy. All patients receiving adalimumab for the treatment of HS with at least 1 follow-up visit 3 or more months after treatment initiation were included. Duration of treatment with adalimumab was defined as the length of time between initiation and termination of adalimumab, regardless of flares, adverse events, or addition of adjuvant therapy that occurred during this time span. Because standardized rating scales measuring the severity of HS at this time are not recorded routinely at our institution, treatment duration with adalimumab was used as a surrogate for measuring therapeutic success. Additionally, treatment duration is a meaningful end point, as patients with HS may require indefinite treatment. Patients were eligible for inclusion if they were receiving adalimumab for the treatment of HS. Patients were excluded if they were lost to follow-up or had received adalimumab for less than 6 months, as data suggest that biologics do not reach peak effect for up to 6 months in HS.⁴

We identified 116 eligible patients with HS, 32 of whom received combination therapy. Five patients received 40 mg of adalimumab every other week, and 111 patients received 40 mg of adalimumab each week. Patients receiving oral immunosuppressants were more likely to be male and as likely to be biologic naïve compared to patients on monotherapy (Table). The average weekly dose of MTX was 14.63 mg, and the average daily dose of MMF was 1000 mg. The average number of days between starting adalimumab and starting an oral immunosuppressant was 114.5 (SD, 217; median, 0) days. Reasons for discontinuation of adalimumab included insufficient response, noncompliance, dislike of injections, adverse events, fear of adverse events, other medical issues unrelated to HS, and insurance coverage issues. Patients who ended treatment with adalimumab owing to insurance coverage issues were still included in our study because insurance coverage remains a major determinant of treatment choice in HS and is relevant to the dynamics of medical decision-making.

Statistical analysis was conducted on all patients inclusive of any reason for discontinuation to avoid bias in the calculation of treatment duration. Cox regression analysis was conducted for all independent variables and was noncontributory. Kaplan-Meier methodology was used to assess the duration of treatment of adalimumab with and without concomitant oral immunosuppressants, and quartile survival times were calculated. Quartile survival time is the time point after adalimumab initiation at which 25% of patients have discontinued adalimumab. We chose quartile survival time instead of average treatment duration to adequately power this study, given our small patient pool.

Although patients receiving adalimumab with oral immunosuppressants had a longer quartile treatment duration (450 days; 95% CI, 185-1800) than the group without oral immunosuppressants (360 days; 95% CI, 200-700), neither MTX nor MMF was shown to significantly prolong duration of therapy with adalimumab (log-rank test: P=.12). Additionally, patients receiving combination therapy were just as likely to discontinue adalimumab as those on monotherapy (χ² test: P=.93). Patients who took both MTX and MMF at different times did show a statistically significant increase in adalimumab quartile treatment duration (1710 days; 95% CI, 1620 [upper limit not calculable]), but this is likely because these patients were kept on adalimumab while trialing adjunctive medications.

The results of our study indicate that MTX and MMF do not prolong duration of adalimumab therapy, which suggests that adalimumab combination therapy with MTX and MMF may not improve HS more than adalimumab alone, and/or partial responders to adalimumab monotherapy are unlikely to be converted to satisfactory responders with the addition of oral immunosuppressants. Limitations of our study include that it was retrospective, used treatment duration as a surrogate for objective efficacy measures, and relied on a single-institution data source. Additionally, owing to our small sample size, we were unable to account for certain potential confounders, including patient weight and insurance status. Future controlled prospective studies using objective end points are needed to further elucidate whether oral immunosuppressants have a role as an adjunct in the treatment of HS.

To the Editor:

The tumor necrosis factor α inhibitor adalimumab is the only US Food and Drug Administration–approved treatment of hidradenitis suppurativa (HS). Although 50.6% of patients fulfilled Hidradenitis Suppurativa Clinical Response criteria with adalimumab at 12 weeks, many responders were not satisfied with their disease control, and secondary loss of Hidradenitis Suppurativa Clinical Response fulfillment occurred in 15.9% of patients within approximately 3 years.¹ Without other US Food and Drug Administration–approved HS treatments, some dermatologists have combined adalimumab with methotrexate (MTX) and/or mycophenolate mofetil (MMF) to attempt to increase the duration of satisfactory disease control while on adalimumab. Combining tumor necrosis factor α inhibitors with oral immunosuppressants is a well-established approach in psoriasis, psoriatic arthritis, and inflammatory bowel disease; however, to the best of our knowledge, this approach has not been studied for HS.^2,3

To assess whether there is a role for combining adalimumab with MTX and/or MMF in the treatment of HS, we performed a single-institution retrospective chart review at the University of Connecticut Department of Dermatology to determine whether patients receiving combination therapy stayed on adalimumab longer than those who received adalimumab monotherapy. All patients receiving adalimumab for the treatment of HS with at least 1 follow-up visit 3 or more months after treatment initiation were included. Duration of treatment with adalimumab was defined as the length of time between initiation and termination of adalimumab, regardless of flares, adverse events, or addition of adjuvant therapy that occurred during this time span. Because standardized rating scales measuring the severity of HS at this time are not recorded routinely at our institution, treatment duration with adalimumab was used as a surrogate for measuring therapeutic success. Additionally, treatment duration is a meaningful end point, as patients with HS may require indefinite treatment. Patients were eligible for inclusion if they were receiving adalimumab for the treatment of HS. Patients were excluded if they were lost to follow-up or had received adalimumab for less than 6 months, as data suggest that biologics do not reach peak effect for up to 6 months in HS.⁴

We identified 116 eligible patients with HS, 32 of whom received combination therapy. Five patients received 40 mg of adalimumab every other week, and 111 patients received 40 mg of adalimumab each week. Patients receiving oral immunosuppressants were more likely to be male and as likely to be biologic naïve compared to patients on monotherapy (Table). The average weekly dose of MTX was 14.63 mg, and the average daily dose of MMF was 1000 mg. The average number of days between starting adalimumab and starting an oral immunosuppressant was 114.5 (SD, 217; median, 0) days. Reasons for discontinuation of adalimumab included insufficient response, noncompliance, dislike of injections, adverse events, fear of adverse events, other medical issues unrelated to HS, and insurance coverage issues. Patients who ended treatment with adalimumab owing to insurance coverage issues were still included in our study because insurance coverage remains a major determinant of treatment choice in HS and is relevant to the dynamics of medical decision-making.

Statistical analysis was conducted on all patients inclusive of any reason for discontinuation to avoid bias in the calculation of treatment duration. Cox regression analysis was conducted for all independent variables and was noncontributory. Kaplan-Meier methodology was used to assess the duration of treatment of adalimumab with and without concomitant oral immunosuppressants, and quartile survival times were calculated. Quartile survival time is the time point after adalimumab initiation at which 25% of patients have discontinued adalimumab. We chose quartile survival time instead of average treatment duration to adequately power this study, given our small patient pool.

Although patients receiving adalimumab with oral immunosuppressants had a longer quartile treatment duration (450 days; 95% CI, 185-1800) than the group without oral immunosuppressants (360 days; 95% CI, 200-700), neither MTX nor MMF was shown to significantly prolong duration of therapy with adalimumab (log-rank test: P=.12). Additionally, patients receiving combination therapy were just as likely to discontinue adalimumab as those on monotherapy (χ² test: P=.93). Patients who took both MTX and MMF at different times did show a statistically significant increase in adalimumab quartile treatment duration (1710 days; 95% CI, 1620 [upper limit not calculable]), but this is likely because these patients were kept on adalimumab while trialing adjunctive medications.

The results of our study indicate that MTX and MMF do not prolong duration of adalimumab therapy, which suggests that adalimumab combination therapy with MTX and MMF may not improve HS more than adalimumab alone, and/or partial responders to adalimumab monotherapy are unlikely to be converted to satisfactory responders with the addition of oral immunosuppressants. Limitations of our study include that it was retrospective, used treatment duration as a surrogate for objective efficacy measures, and relied on a single-institution data source. Additionally, owing to our small sample size, we were unable to account for certain potential confounders, including patient weight and insurance status. Future controlled prospective studies using objective end points are needed to further elucidate whether oral immunosuppressants have a role as an adjunct in the treatment of HS.

To the Editor:

The tumor necrosis factor α inhibitor adalimumab is the only US Food and Drug Administration–approved treatment of hidradenitis suppurativa (HS). Although 50.6% of patients fulfilled Hidradenitis Suppurativa Clinical Response criteria with adalimumab at 12 weeks, many responders were not satisfied with their disease control, and secondary loss of Hidradenitis Suppurativa Clinical Response fulfillment occurred in 15.9% of patients within approximately 3 years.¹ Without other US Food and Drug Administration–approved HS treatments, some dermatologists have combined adalimumab with methotrexate (MTX) and/or mycophenolate mofetil (MMF) to attempt to increase the duration of satisfactory disease control while on adalimumab. Combining tumor necrosis factor α inhibitors with oral immunosuppressants is a well-established approach in psoriasis, psoriatic arthritis, and inflammatory bowel disease; however, to the best of our knowledge, this approach has not been studied for HS.^2,3

To assess whether there is a role for combining adalimumab with MTX and/or MMF in the treatment of HS, we performed a single-institution retrospective chart review at the University of Connecticut Department of Dermatology to determine whether patients receiving combination therapy stayed on adalimumab longer than those who received adalimumab monotherapy. All patients receiving adalimumab for the treatment of HS with at least 1 follow-up visit 3 or more months after treatment initiation were included. Duration of treatment with adalimumab was defined as the length of time between initiation and termination of adalimumab, regardless of flares, adverse events, or addition of adjuvant therapy that occurred during this time span. Because standardized rating scales measuring the severity of HS at this time are not recorded routinely at our institution, treatment duration with adalimumab was used as a surrogate for measuring therapeutic success. Additionally, treatment duration is a meaningful end point, as patients with HS may require indefinite treatment. Patients were eligible for inclusion if they were receiving adalimumab for the treatment of HS. Patients were excluded if they were lost to follow-up or had received adalimumab for less than 6 months, as data suggest that biologics do not reach peak effect for up to 6 months in HS.⁴

We identified 116 eligible patients with HS, 32 of whom received combination therapy. Five patients received 40 mg of adalimumab every other week, and 111 patients received 40 mg of adalimumab each week. Patients receiving oral immunosuppressants were more likely to be male and as likely to be biologic naïve compared to patients on monotherapy (Table). The average weekly dose of MTX was 14.63 mg, and the average daily dose of MMF was 1000 mg. The average number of days between starting adalimumab and starting an oral immunosuppressant was 114.5 (SD, 217; median, 0) days. Reasons for discontinuation of adalimumab included insufficient response, noncompliance, dislike of injections, adverse events, fear of adverse events, other medical issues unrelated to HS, and insurance coverage issues. Patients who ended treatment with adalimumab owing to insurance coverage issues were still included in our study because insurance coverage remains a major determinant of treatment choice in HS and is relevant to the dynamics of medical decision-making.

Statistical analysis was conducted on all patients inclusive of any reason for discontinuation to avoid bias in the calculation of treatment duration. Cox regression analysis was conducted for all independent variables and was noncontributory. Kaplan-Meier methodology was used to assess the duration of treatment of adalimumab with and without concomitant oral immunosuppressants, and quartile survival times were calculated. Quartile survival time is the time point after adalimumab initiation at which 25% of patients have discontinued adalimumab. We chose quartile survival time instead of average treatment duration to adequately power this study, given our small patient pool.

Although patients receiving adalimumab with oral immunosuppressants had a longer quartile treatment duration (450 days; 95% CI, 185-1800) than the group without oral immunosuppressants (360 days; 95% CI, 200-700), neither MTX nor MMF was shown to significantly prolong duration of therapy with adalimumab (log-rank test: P=.12). Additionally, patients receiving combination therapy were just as likely to discontinue adalimumab as those on monotherapy (χ² test: P=.93). Patients who took both MTX and MMF at different times did show a statistically significant increase in adalimumab quartile treatment duration (1710 days; 95% CI, 1620 [upper limit not calculable]), but this is likely because these patients were kept on adalimumab while trialing adjunctive medications.

The results of our study indicate that MTX and MMF do not prolong duration of adalimumab therapy, which suggests that adalimumab combination therapy with MTX and MMF may not improve HS more than adalimumab alone, and/or partial responders to adalimumab monotherapy are unlikely to be converted to satisfactory responders with the addition of oral immunosuppressants. Limitations of our study include that it was retrospective, used treatment duration as a surrogate for objective efficacy measures, and relied on a single-institution data source. Additionally, owing to our small sample size, we were unable to account for certain potential confounders, including patient weight and insurance status. Future controlled prospective studies using objective end points are needed to further elucidate whether oral immunosuppressants have a role as an adjunct in the treatment of HS.

Practice Gap

The Sarcoptes scabiei mite is a microscopic organism that causes scabies in the human host. The scabies mite is highly transmissible, making scabies a common disease in heavily populated areas. The mite survives by burrowing into the epidermis, where it feeds, lays eggs, and defecates.¹

The rash in the host represents an allergic reaction to the body of the scabies mite, producing symptoms such as intense itching, rash, and erosions of the skin. The scabies rash tends to occur in warm and occluded areas of the body such as the hands, axillae, groin, buttocks, and feet.^1,2

Delaying treatment of scabies can be hazardous because of the risk of rapid spread from one person to another. This rapid spread can be debilitating in specific populations, such as the immunocompromised, elderly, and disabled.

Mineral oil preparation is the classic method used to identify scabies (Figure 1). This method relies on obtaining mites by applying mineral oil to the skin and using a 15-mm blade to scrape off layers of the affected skin. The scraped material is spread onto a microscope slide with mineral oil, a coverslip is applied, and the specimen is analyzed by direct microscopy. This method proves only as effective as knowing where the few mites are located.

At any time, only 10 to 12 mites live on a human host.³ Therefore, it can be challenging to obtain a mite for diagnosis because the location of the skin mites may be unknown. Dermoscopy can be used to locate burrows and other signs of S scabiei. With a dermatoscope, the scabies mite can be identified by the so-called delta-wing jet sign.⁴

However, dermoscopy is not always successful because extensive hemorrhagic crusting and erosions of the skin secondary to constant scratching can obscure the appearance of burrows and mites. Because patients are constantly scratching areas of irritation, it is possible that S scabiei can be located under the fingernail of the dominant hand.

The Technique

To address this practice gap, a mineral oil scabies preparation can be performed by scraping under the fingernail plate at the level of the hyponychium. Mites might accumulate underneath the fingernails of the dominant hand when patients scratch the area of the skin where S scabiei mites are burrowing and reproducing.

A convenient and painless way to obtain a mineral oil scabies preparation from under the fingernail is to use the tip of a disposable hyfrecator, readily available in most dermatology practices for use in electrosurgery (Figure 2). Using the blunt end of the hyfrecator tip for the mineral oil preparation would be done without attachment to the full apparatus.

The hyponychium of the fingernail is prepared with mineral oil, which aids in collecting and suspending the material obtained from under the nail plate. Using the blunt end of the hyfrecator tip, material from underneath the fingernail is removed using a gentle sweeping motion (Figure 3). The specimen is then analyzed under the microscope similar to a routine mineral oil scabies preparation. This method can be utilized by health care providers for easy and painless diagnosis of scabies.

Practice Implications

Use of a blunt hyfrecator tip to extract S scabiei from underneath the fingernail plate can be used for efficient diagnosis of scabies. This technique can be implemented in any clinic where blunt-tip hyfrecator electrodes are available. Using a gentle sweeping motion, the blunt-tip hyfrecator allows the provider to extract material from under the fingernail for diagnosis. The material obtained is used to prepare a mineral oil scabies preparation for direct microscopic analysis.

This technique can diagnose scabies efficiently, and treatment can be initiated promptly. Use of a disposable blunt-tip hyfrecator for scabies extraction is a novel technique that can be added to the armamentarium of tools to diagnose scabies, which includes traditional mineral oil preparation and dermoscopy.

Practice Gap

The Sarcoptes scabiei mite is a microscopic organism that causes scabies in the human host. The scabies mite is highly transmissible, making scabies a common disease in heavily populated areas. The mite survives by burrowing into the epidermis, where it feeds, lays eggs, and defecates.¹

The rash in the host represents an allergic reaction to the body of the scabies mite, producing symptoms such as intense itching, rash, and erosions of the skin. The scabies rash tends to occur in warm and occluded areas of the body such as the hands, axillae, groin, buttocks, and feet.^1,2

Delaying treatment of scabies can be hazardous because of the risk of rapid spread from one person to another. This rapid spread can be debilitating in specific populations, such as the immunocompromised, elderly, and disabled.

Mineral oil preparation is the classic method used to identify scabies (Figure 1). This method relies on obtaining mites by applying mineral oil to the skin and using a 15-mm blade to scrape off layers of the affected skin. The scraped material is spread onto a microscope slide with mineral oil, a coverslip is applied, and the specimen is analyzed by direct microscopy. This method proves only as effective as knowing where the few mites are located.

At any time, only 10 to 12 mites live on a human host.³ Therefore, it can be challenging to obtain a mite for diagnosis because the location of the skin mites may be unknown. Dermoscopy can be used to locate burrows and other signs of S scabiei. With a dermatoscope, the scabies mite can be identified by the so-called delta-wing jet sign.⁴

However, dermoscopy is not always successful because extensive hemorrhagic crusting and erosions of the skin secondary to constant scratching can obscure the appearance of burrows and mites. Because patients are constantly scratching areas of irritation, it is possible that S scabiei can be located under the fingernail of the dominant hand.

The Technique

To address this practice gap, a mineral oil scabies preparation can be performed by scraping under the fingernail plate at the level of the hyponychium. Mites might accumulate underneath the fingernails of the dominant hand when patients scratch the area of the skin where S scabiei mites are burrowing and reproducing.

A convenient and painless way to obtain a mineral oil scabies preparation from under the fingernail is to use the tip of a disposable hyfrecator, readily available in most dermatology practices for use in electrosurgery (Figure 2). Using the blunt end of the hyfrecator tip for the mineral oil preparation would be done without attachment to the full apparatus.

The hyponychium of the fingernail is prepared with mineral oil, which aids in collecting and suspending the material obtained from under the nail plate. Using the blunt end of the hyfrecator tip, material from underneath the fingernail is removed using a gentle sweeping motion (Figure 3). The specimen is then analyzed under the microscope similar to a routine mineral oil scabies preparation. This method can be utilized by health care providers for easy and painless diagnosis of scabies.

Practice Implications

Use of a blunt hyfrecator tip to extract S scabiei from underneath the fingernail plate can be used for efficient diagnosis of scabies. This technique can be implemented in any clinic where blunt-tip hyfrecator electrodes are available. Using a gentle sweeping motion, the blunt-tip hyfrecator allows the provider to extract material from under the fingernail for diagnosis. The material obtained is used to prepare a mineral oil scabies preparation for direct microscopic analysis.

This technique can diagnose scabies efficiently, and treatment can be initiated promptly. Use of a disposable blunt-tip hyfrecator for scabies extraction is a novel technique that can be added to the armamentarium of tools to diagnose scabies, which includes traditional mineral oil preparation and dermoscopy.

Practice Gap

The Sarcoptes scabiei mite is a microscopic organism that causes scabies in the human host. The scabies mite is highly transmissible, making scabies a common disease in heavily populated areas. The mite survives by burrowing into the epidermis, where it feeds, lays eggs, and defecates.¹

The rash in the host represents an allergic reaction to the body of the scabies mite, producing symptoms such as intense itching, rash, and erosions of the skin. The scabies rash tends to occur in warm and occluded areas of the body such as the hands, axillae, groin, buttocks, and feet.^1,2

Delaying treatment of scabies can be hazardous because of the risk of rapid spread from one person to another. This rapid spread can be debilitating in specific populations, such as the immunocompromised, elderly, and disabled.

Mineral oil preparation is the classic method used to identify scabies (Figure 1). This method relies on obtaining mites by applying mineral oil to the skin and using a 15-mm blade to scrape off layers of the affected skin. The scraped material is spread onto a microscope slide with mineral oil, a coverslip is applied, and the specimen is analyzed by direct microscopy. This method proves only as effective as knowing where the few mites are located.

At any time, only 10 to 12 mites live on a human host.³ Therefore, it can be challenging to obtain a mite for diagnosis because the location of the skin mites may be unknown. Dermoscopy can be used to locate burrows and other signs of S scabiei. With a dermatoscope, the scabies mite can be identified by the so-called delta-wing jet sign.⁴

However, dermoscopy is not always successful because extensive hemorrhagic crusting and erosions of the skin secondary to constant scratching can obscure the appearance of burrows and mites. Because patients are constantly scratching areas of irritation, it is possible that S scabiei can be located under the fingernail of the dominant hand.

The Technique

To address this practice gap, a mineral oil scabies preparation can be performed by scraping under the fingernail plate at the level of the hyponychium. Mites might accumulate underneath the fingernails of the dominant hand when patients scratch the area of the skin where S scabiei mites are burrowing and reproducing.

A convenient and painless way to obtain a mineral oil scabies preparation from under the fingernail is to use the tip of a disposable hyfrecator, readily available in most dermatology practices for use in electrosurgery (Figure 2). Using the blunt end of the hyfrecator tip for the mineral oil preparation would be done without attachment to the full apparatus.

The hyponychium of the fingernail is prepared with mineral oil, which aids in collecting and suspending the material obtained from under the nail plate. Using the blunt end of the hyfrecator tip, material from underneath the fingernail is removed using a gentle sweeping motion (Figure 3). The specimen is then analyzed under the microscope similar to a routine mineral oil scabies preparation. This method can be utilized by health care providers for easy and painless diagnosis of scabies.

Practice Implications

Use of a blunt hyfrecator tip to extract S scabiei from underneath the fingernail plate can be used for efficient diagnosis of scabies. This technique can be implemented in any clinic where blunt-tip hyfrecator electrodes are available. Using a gentle sweeping motion, the blunt-tip hyfrecator allows the provider to extract material from under the fingernail for diagnosis. The material obtained is used to prepare a mineral oil scabies preparation for direct microscopic analysis.

This technique can diagnose scabies efficiently, and treatment can be initiated promptly. Use of a disposable blunt-tip hyfrecator for scabies extraction is a novel technique that can be added to the armamentarium of tools to diagnose scabies, which includes traditional mineral oil preparation and dermoscopy.

More than half a million individuals are without housing (NWH) on any given night in the United States, as estimated by the US Department of Housing and Urban Development. ¹ Lack of hygiene, increased risk of infection and infestation due to living conditions, and barriers to health care put these individuals at increased risk for disease. ² Skin disease, including fungal infection and acne, are within the top 10 most prevalent diseases worldwide and can cause major psychologic impairment, yet dermatologic concerns and clinical outcomes in NWH patients have not been well characterized. ^2-5 Further, because this vulnerable demographic tends to be underinsured, they frequently present to the emergency department (ED) for management of disease. ^1,6 Survey of common concerns in NWH patients is of utility to consulting dermatologists and nondermatologist providers in the ED, who can familiarize themselves with management of diseases they are more likely to encounter. Few studies examine dermatologic conditions in the ED, and a thorough literature review indicates none have included homelessness as a variable. ^6,7 Additionally, comparison with a matched control group of patients with housing (WH) is limited. ^5,8 We present one of the largest comparisons of cutaneous disease in NWH vs WH patients in a single hospital system to elucidate the types of cutaneous disease that motivate patients to seek care, the location of skin disease, and differences in clinical care.

Methods

A retrospective medical record review of patients seen for an inclusive list of dermatologic diagnoses in the ED or while admitted at University Medical Center New Orleans, Louisiana (UMC), between January 1, 2018, and April 21, 2020, was conducted. This study was qualified as exempt from the institutional review board by Louisiana State University because it proposed zero risk to the patients and remained completely anonymous. Eight hundred forty-two total medical records were reviewed (NWH, 421; WH, 421)(Table 1). Patients with housing were matched based on self-identified race and ethnicity, sex, and age. Disease categories were constructed based on fundamental pathophysiology adapted from Dermatology⁹: infectious, noninfectious inflammatory, neoplasm, trauma and wounds, drug-related eruptions, vascular, pruritic, pigmented, bullous, neuropsychiatric, and other. Other included unspecified eruptions as well as miscellaneous lesions such as calluses. The current chief concern, anatomic location, and configuration were recorded, as well as biopsied lesions and outpatient referrals or inpatient consultations to dermatology or other specialties, including wound care, infectious disease, podiatry, and surgery. χ² analysis was used to analyze significance of cutaneous categories, body location, and referrals. Groups smaller than 5 defaulted to the Fisher exact test.

Results

The total diagnoses (including both chief concerns and secondary diagnoses) are shown in Table 2. Chief concerns were more frequently cutaneous or dermatologic for WH (NWH, 209; WH, 307; P<.001). In both groups, cutaneous infectious etiologies were more likely to be a patient’s presenting chief concern (58% NWH, P=.002; 42% WH, P<.001). Noninfectious inflammatory etiologies and pigmented lesions were more likely to be secondary diagnoses with an unrelated noncutaneous concern; noninfectious inflammatory etiologies were only 16% of the total cutaneous chief concerns (11% NWH, P=.04; 20% WH, P=.03), and no pigmented lesions were chief concerns.

Infection was the most common chief concern, though NWH patients presented with significantly more infectious concerns (NWH, 212; WH, 150; P<.001), particularly infestations (NWH, 33; WH, 8; P<.001) and bacterial etiologies (NWH, 127; WH, 100; P=.04). The majority of bacterial etiologies were either an abscess or cellulitis (NWH, 106; WH, 83), though infected chronic wounds were categorized as bacterial infection when treated definitively as such (eg, in the case of sacral ulcers causing osteomyelitis)(NWH, 21; WH, 17). Of note, infectious etiology was associated with intravenous drug use (IVDU) in both NWH and WH patients. Of 184 NWH who reported IVDU, 127 had an infectious diagnosis (P<.001). Similarly, 43 of 56 total WH patients who reported IVDU had an infectious diagnosis (P<.001). Infestation (within the infectious category) included scabies (NWH, 20; WH, 3) and insect or arthropod bites (NWH, 12; WH, 5). Two NWH patients also presented with swelling of the lower extremities and were subsequently diagnosed with maggot infestations. Fungal and viral etiologies were not significantly increased in either group; however, NWH did have a higher incidence of tinea pedis (NWH, 14; WH, 4; P=.03).

More neoplasms (NWH, 6; WH, 16; P=.03), noninfectious inflammatory eruptions (NWH, 48; WH, 85; P<.001), and cutaneous drug eruptions (NWH, 5; WH, 27; P<.001) were reported in WH patients. There was no significant difference in benign vs malignant neoplastic processes between groups. More noninfectious inflammatory eruptions in WH were specifically driven by a markedly increased incidence of follicular (NWH, 9; WH, 29; P<.001) and urticarial/erythematous (NWH, 3; WH, 13; P=.02) lesions. Follicular etiologies included acne (NWH, 1; WH, 6; P=.12), folliculitis (NWH, 5; WH, 2; P=.45), hidradenitis suppurativa (NWH, 2; WH, 11; P=.02), and pilonidal and sebaceous cysts (NWH, 1; WH, 10; P=.01). Allergic urticaria dominated the urticarial/erythematous category (NWH, 3; WH, 11; P=.06), though there were 2 WH presentations of diffuse erythema and skin peeling.

Another substantial proportion of cutaneous etiologies were due to trauma or chronic wounds. Significantly more traumatic injuries presented in NWH patients vs WH patients (36 vs 31; P=.04). Trauma included human or dog bites (NWH, 5; WH, 4), sunburns (NWH, 3; WH, 0), other burns (NWH, 11; WH, 13), abrasions and lacerations (NWH, 16; WH, 3; P=.004), and foreign bodies (NWH, 1; WH, 1). Wounds consisted of chronic wounds such as those due to diabetes mellitus (foot ulcers) or immobility (sacral ulcers); numbers were similar between groups.

Looking at location, NWH patients had more pathology on the feet (NWH, 62; WH, 39; P=.02), whereas WH patients had more disseminated multiregional concerns (NWH, 55; WH, 75; P=.05). No one body location was notably more likely to warrant a chief concern.

For clinical outcomes, more WH patients received a consultation of any kind (NWH, 171; WH, 217; P<.001), consultation to dermatology (NWH, 49; WH, 87; P<.001), and consultation to surgery (NWH, 64; WH, 110; P<.001)(Table 3 and Figure). More outpatient referrals to dermatology were made for WH patients (NWH, 61; WH, 82; P=.05). Notably, NWH patients presented for 80% fewer hospital follow-up appointments (NWH, 11; WH, 55; P<.001). It is essential to note that these findings were not affected by self-reported race or ethnicity. Results remained significant when broken into cohorts consisting of patients with and without skin of color.

Comment

Cutaneous Concerns in NWH Patients—Although cutaneous disease has been reported to disproportionately affect NWH patients,¹⁰ in our cohort, NWH patients had fewer cutaneous chief concerns than WH patients. However, without comparing with all patients entering the ED at UMC, we cannot make a statement on this claim. We do present a few reasons why NWH patients do not have more cutaneous concerns. First, they may wait to present with cutaneous disease until it becomes more severe (eg, until chronic wounds have progressed to infections). Second, as discussed in depth by Hollestein and Nijsten,³ dermatologic disease may be a major contributor to the overall count of disability-adjusted life years but may play a minor role in individual disability. Therefore, skin disease often is considered less important on an individual basis, despite substantial psychosocial burden, leading to further stigmatization of this vulnerable population and discouraged care-seeking behavior, particularly for noninfectious inflammatory eruptions, which were notably more present in WH individuals. Third, fewer dermatologic lesions were reported on NWH patients, which may explain why all 3 WH pigmented lesions were diagnosed after presentation with a noncutaneous concern (eg, headache, anemia, nausea).

Infectious Cutaneous Diagnoses—The increased presentation of infectious etiologies, especially bacterial, is linked to the increased numbers of IVDUs reported in NWH individuals as well as increased exposure and decreased access to basic hygienic supplies. Intravenous drug use acted as an effect modifier of infectious etiology diagnoses, playing a major role in both NWH and WH cohorts. Although Black and Hispanic individuals as well as individuals with low socioeconomic status have increased proportions of skin cancer, there are inadequate data on the prevalence in NWH individuals.⁴ We found no increase in malignant dermatologic processes in NWH individuals; however, this may be secondary to inadequate screening with a total body skin examination.

Clinical Workup of NWH Patients—Because most NWH individuals present to the ED to receive care, their care compared with WH patients should be considered. In this cohort, WH patients received a less extensive clinical workup. They received almost half as many dermatologic consultations and fewer outpatient referrals to dermatology. Major communication barriers may affect NWH presentation to follow-up, which was drastically lower than WH individuals, as scheduling typically occurs well after discharge from the ED or inpatient unit. We suggest a few alterations to improve dermatologic care for NWH individuals:

• Consider inpatient consultation for serious dermatologic conditions—even if chronic—to improve disease control, considering that many barriers inhibit follow-up in clinic.

• Involve outreach teams, such as the Assertive Community Treatment teams, that assist individuals by delivering medicine for psychiatric disorders, conducting total-body skin examinations, assisting with wound care, providing basic skin barrier creams or medicaments, and carrying information regarding outpatient follow-up.

• Educate ED providers on the most common skin concerns, especially those that fall within the noninfectious inflammatory category, such as hidradenitis suppurativa, which could easily be misdiagnosed as an abscess.

Future Directions—Owing to limitations of a retrospective cohort study, we present several opportunities for further research on this vulnerable population. The severity of disease, especially infectious etiologies, should be graded to determine if NWH patients truly present later in the disease course. The duration and quality of housing for NWH patients could be categorized based on living conditions (eg, on the street vs in a shelter). Although the findings of our NWH cohort presenting to the ED at UMC provide helpful insight into dermatologic disease, these findings may be disparate from those conducted at other locations in the United States. University Medical Center provides care to mostly subsidized insurance plans in a racially diverse community. Improved outcomes for the NWH individuals living in New Orleans start with obtaining a greater understanding of their diseases and where disparities exist that can be bridged with better care.

Acknowledgment—The dataset generated during this study and used for analysis is not publicly available to protect public health information but is available from the corresponding author on reasonable request.

More than half a million individuals are without housing (NWH) on any given night in the United States, as estimated by the US Department of Housing and Urban Development. ¹ Lack of hygiene, increased risk of infection and infestation due to living conditions, and barriers to health care put these individuals at increased risk for disease. ² Skin disease, including fungal infection and acne, are within the top 10 most prevalent diseases worldwide and can cause major psychologic impairment, yet dermatologic concerns and clinical outcomes in NWH patients have not been well characterized. ^2-5 Further, because this vulnerable demographic tends to be underinsured, they frequently present to the emergency department (ED) for management of disease. ^1,6 Survey of common concerns in NWH patients is of utility to consulting dermatologists and nondermatologist providers in the ED, who can familiarize themselves with management of diseases they are more likely to encounter. Few studies examine dermatologic conditions in the ED, and a thorough literature review indicates none have included homelessness as a variable. ^6,7 Additionally, comparison with a matched control group of patients with housing (WH) is limited. ^5,8 We present one of the largest comparisons of cutaneous disease in NWH vs WH patients in a single hospital system to elucidate the types of cutaneous disease that motivate patients to seek care, the location of skin disease, and differences in clinical care.

Methods

A retrospective medical record review of patients seen for an inclusive list of dermatologic diagnoses in the ED or while admitted at University Medical Center New Orleans, Louisiana (UMC), between January 1, 2018, and April 21, 2020, was conducted. This study was qualified as exempt from the institutional review board by Louisiana State University because it proposed zero risk to the patients and remained completely anonymous. Eight hundred forty-two total medical records were reviewed (NWH, 421; WH, 421)(Table 1). Patients with housing were matched based on self-identified race and ethnicity, sex, and age. Disease categories were constructed based on fundamental pathophysiology adapted from Dermatology⁹: infectious, noninfectious inflammatory, neoplasm, trauma and wounds, drug-related eruptions, vascular, pruritic, pigmented, bullous, neuropsychiatric, and other. Other included unspecified eruptions as well as miscellaneous lesions such as calluses. The current chief concern, anatomic location, and configuration were recorded, as well as biopsied lesions and outpatient referrals or inpatient consultations to dermatology or other specialties, including wound care, infectious disease, podiatry, and surgery. χ² analysis was used to analyze significance of cutaneous categories, body location, and referrals. Groups smaller than 5 defaulted to the Fisher exact test.

Results

The total diagnoses (including both chief concerns and secondary diagnoses) are shown in Table 2. Chief concerns were more frequently cutaneous or dermatologic for WH (NWH, 209; WH, 307; P<.001). In both groups, cutaneous infectious etiologies were more likely to be a patient’s presenting chief concern (58% NWH, P=.002; 42% WH, P<.001). Noninfectious inflammatory etiologies and pigmented lesions were more likely to be secondary diagnoses with an unrelated noncutaneous concern; noninfectious inflammatory etiologies were only 16% of the total cutaneous chief concerns (11% NWH, P=.04; 20% WH, P=.03), and no pigmented lesions were chief concerns.

Infection was the most common chief concern, though NWH patients presented with significantly more infectious concerns (NWH, 212; WH, 150; P<.001), particularly infestations (NWH, 33; WH, 8; P<.001) and bacterial etiologies (NWH, 127; WH, 100; P=.04). The majority of bacterial etiologies were either an abscess or cellulitis (NWH, 106; WH, 83), though infected chronic wounds were categorized as bacterial infection when treated definitively as such (eg, in the case of sacral ulcers causing osteomyelitis)(NWH, 21; WH, 17). Of note, infectious etiology was associated with intravenous drug use (IVDU) in both NWH and WH patients. Of 184 NWH who reported IVDU, 127 had an infectious diagnosis (P<.001). Similarly, 43 of 56 total WH patients who reported IVDU had an infectious diagnosis (P<.001). Infestation (within the infectious category) included scabies (NWH, 20; WH, 3) and insect or arthropod bites (NWH, 12; WH, 5). Two NWH patients also presented with swelling of the lower extremities and were subsequently diagnosed with maggot infestations. Fungal and viral etiologies were not significantly increased in either group; however, NWH did have a higher incidence of tinea pedis (NWH, 14; WH, 4; P=.03).

More neoplasms (NWH, 6; WH, 16; P=.03), noninfectious inflammatory eruptions (NWH, 48; WH, 85; P<.001), and cutaneous drug eruptions (NWH, 5; WH, 27; P<.001) were reported in WH patients. There was no significant difference in benign vs malignant neoplastic processes between groups. More noninfectious inflammatory eruptions in WH were specifically driven by a markedly increased incidence of follicular (NWH, 9; WH, 29; P<.001) and urticarial/erythematous (NWH, 3; WH, 13; P=.02) lesions. Follicular etiologies included acne (NWH, 1; WH, 6; P=.12), folliculitis (NWH, 5; WH, 2; P=.45), hidradenitis suppurativa (NWH, 2; WH, 11; P=.02), and pilonidal and sebaceous cysts (NWH, 1; WH, 10; P=.01). Allergic urticaria dominated the urticarial/erythematous category (NWH, 3; WH, 11; P=.06), though there were 2 WH presentations of diffuse erythema and skin peeling.

Another substantial proportion of cutaneous etiologies were due to trauma or chronic wounds. Significantly more traumatic injuries presented in NWH patients vs WH patients (36 vs 31; P=.04). Trauma included human or dog bites (NWH, 5; WH, 4), sunburns (NWH, 3; WH, 0), other burns (NWH, 11; WH, 13), abrasions and lacerations (NWH, 16; WH, 3; P=.004), and foreign bodies (NWH, 1; WH, 1). Wounds consisted of chronic wounds such as those due to diabetes mellitus (foot ulcers) or immobility (sacral ulcers); numbers were similar between groups.

Looking at location, NWH patients had more pathology on the feet (NWH, 62; WH, 39; P=.02), whereas WH patients had more disseminated multiregional concerns (NWH, 55; WH, 75; P=.05). No one body location was notably more likely to warrant a chief concern.

For clinical outcomes, more WH patients received a consultation of any kind (NWH, 171; WH, 217; P<.001), consultation to dermatology (NWH, 49; WH, 87; P<.001), and consultation to surgery (NWH, 64; WH, 110; P<.001)(Table 3 and Figure). More outpatient referrals to dermatology were made for WH patients (NWH, 61; WH, 82; P=.05). Notably, NWH patients presented for 80% fewer hospital follow-up appointments (NWH, 11; WH, 55; P<.001). It is essential to note that these findings were not affected by self-reported race or ethnicity. Results remained significant when broken into cohorts consisting of patients with and without skin of color.

Comment

Cutaneous Concerns in NWH Patients—Although cutaneous disease has been reported to disproportionately affect NWH patients,¹⁰ in our cohort, NWH patients had fewer cutaneous chief concerns than WH patients. However, without comparing with all patients entering the ED at UMC, we cannot make a statement on this claim. We do present a few reasons why NWH patients do not have more cutaneous concerns. First, they may wait to present with cutaneous disease until it becomes more severe (eg, until chronic wounds have progressed to infections). Second, as discussed in depth by Hollestein and Nijsten,³ dermatologic disease may be a major contributor to the overall count of disability-adjusted life years but may play a minor role in individual disability. Therefore, skin disease often is considered less important on an individual basis, despite substantial psychosocial burden, leading to further stigmatization of this vulnerable population and discouraged care-seeking behavior, particularly for noninfectious inflammatory eruptions, which were notably more present in WH individuals. Third, fewer dermatologic lesions were reported on NWH patients, which may explain why all 3 WH pigmented lesions were diagnosed after presentation with a noncutaneous concern (eg, headache, anemia, nausea).

Infectious Cutaneous Diagnoses—The increased presentation of infectious etiologies, especially bacterial, is linked to the increased numbers of IVDUs reported in NWH individuals as well as increased exposure and decreased access to basic hygienic supplies. Intravenous drug use acted as an effect modifier of infectious etiology diagnoses, playing a major role in both NWH and WH cohorts. Although Black and Hispanic individuals as well as individuals with low socioeconomic status have increased proportions of skin cancer, there are inadequate data on the prevalence in NWH individuals.⁴ We found no increase in malignant dermatologic processes in NWH individuals; however, this may be secondary to inadequate screening with a total body skin examination.

Clinical Workup of NWH Patients—Because most NWH individuals present to the ED to receive care, their care compared with WH patients should be considered. In this cohort, WH patients received a less extensive clinical workup. They received almost half as many dermatologic consultations and fewer outpatient referrals to dermatology. Major communication barriers may affect NWH presentation to follow-up, which was drastically lower than WH individuals, as scheduling typically occurs well after discharge from the ED or inpatient unit. We suggest a few alterations to improve dermatologic care for NWH individuals:

• Consider inpatient consultation for serious dermatologic conditions—even if chronic—to improve disease control, considering that many barriers inhibit follow-up in clinic.

• Involve outreach teams, such as the Assertive Community Treatment teams, that assist individuals by delivering medicine for psychiatric disorders, conducting total-body skin examinations, assisting with wound care, providing basic skin barrier creams or medicaments, and carrying information regarding outpatient follow-up.

• Educate ED providers on the most common skin concerns, especially those that fall within the noninfectious inflammatory category, such as hidradenitis suppurativa, which could easily be misdiagnosed as an abscess.

Future Directions—Owing to limitations of a retrospective cohort study, we present several opportunities for further research on this vulnerable population. The severity of disease, especially infectious etiologies, should be graded to determine if NWH patients truly present later in the disease course. The duration and quality of housing for NWH patients could be categorized based on living conditions (eg, on the street vs in a shelter). Although the findings of our NWH cohort presenting to the ED at UMC provide helpful insight into dermatologic disease, these findings may be disparate from those conducted at other locations in the United States. University Medical Center provides care to mostly subsidized insurance plans in a racially diverse community. Improved outcomes for the NWH individuals living in New Orleans start with obtaining a greater understanding of their diseases and where disparities exist that can be bridged with better care.

Acknowledgment—The dataset generated during this study and used for analysis is not publicly available to protect public health information but is available from the corresponding author on reasonable request.

More than half a million individuals are without housing (NWH) on any given night in the United States, as estimated by the US Department of Housing and Urban Development. ¹ Lack of hygiene, increased risk of infection and infestation due to living conditions, and barriers to health care put these individuals at increased risk for disease. ² Skin disease, including fungal infection and acne, are within the top 10 most prevalent diseases worldwide and can cause major psychologic impairment, yet dermatologic concerns and clinical outcomes in NWH patients have not been well characterized. ^2-5 Further, because this vulnerable demographic tends to be underinsured, they frequently present to the emergency department (ED) for management of disease. ^1,6 Survey of common concerns in NWH patients is of utility to consulting dermatologists and nondermatologist providers in the ED, who can familiarize themselves with management of diseases they are more likely to encounter. Few studies examine dermatologic conditions in the ED, and a thorough literature review indicates none have included homelessness as a variable. ^6,7 Additionally, comparison with a matched control group of patients with housing (WH) is limited. ^5,8 We present one of the largest comparisons of cutaneous disease in NWH vs WH patients in a single hospital system to elucidate the types of cutaneous disease that motivate patients to seek care, the location of skin disease, and differences in clinical care.

Methods

A retrospective medical record review of patients seen for an inclusive list of dermatologic diagnoses in the ED or while admitted at University Medical Center New Orleans, Louisiana (UMC), between January 1, 2018, and April 21, 2020, was conducted. This study was qualified as exempt from the institutional review board by Louisiana State University because it proposed zero risk to the patients and remained completely anonymous. Eight hundred forty-two total medical records were reviewed (NWH, 421; WH, 421)(Table 1). Patients with housing were matched based on self-identified race and ethnicity, sex, and age. Disease categories were constructed based on fundamental pathophysiology adapted from Dermatology⁹: infectious, noninfectious inflammatory, neoplasm, trauma and wounds, drug-related eruptions, vascular, pruritic, pigmented, bullous, neuropsychiatric, and other. Other included unspecified eruptions as well as miscellaneous lesions such as calluses. The current chief concern, anatomic location, and configuration were recorded, as well as biopsied lesions and outpatient referrals or inpatient consultations to dermatology or other specialties, including wound care, infectious disease, podiatry, and surgery. χ² analysis was used to analyze significance of cutaneous categories, body location, and referrals. Groups smaller than 5 defaulted to the Fisher exact test.

Results

The total diagnoses (including both chief concerns and secondary diagnoses) are shown in Table 2. Chief concerns were more frequently cutaneous or dermatologic for WH (NWH, 209; WH, 307; P<.001). In both groups, cutaneous infectious etiologies were more likely to be a patient’s presenting chief concern (58% NWH, P=.002; 42% WH, P<.001). Noninfectious inflammatory etiologies and pigmented lesions were more likely to be secondary diagnoses with an unrelated noncutaneous concern; noninfectious inflammatory etiologies were only 16% of the total cutaneous chief concerns (11% NWH, P=.04; 20% WH, P=.03), and no pigmented lesions were chief concerns.

Infection was the most common chief concern, though NWH patients presented with significantly more infectious concerns (NWH, 212; WH, 150; P<.001), particularly infestations (NWH, 33; WH, 8; P<.001) and bacterial etiologies (NWH, 127; WH, 100; P=.04). The majority of bacterial etiologies were either an abscess or cellulitis (NWH, 106; WH, 83), though infected chronic wounds were categorized as bacterial infection when treated definitively as such (eg, in the case of sacral ulcers causing osteomyelitis)(NWH, 21; WH, 17). Of note, infectious etiology was associated with intravenous drug use (IVDU) in both NWH and WH patients. Of 184 NWH who reported IVDU, 127 had an infectious diagnosis (P<.001). Similarly, 43 of 56 total WH patients who reported IVDU had an infectious diagnosis (P<.001). Infestation (within the infectious category) included scabies (NWH, 20; WH, 3) and insect or arthropod bites (NWH, 12; WH, 5). Two NWH patients also presented with swelling of the lower extremities and were subsequently diagnosed with maggot infestations. Fungal and viral etiologies were not significantly increased in either group; however, NWH did have a higher incidence of tinea pedis (NWH, 14; WH, 4; P=.03).

More neoplasms (NWH, 6; WH, 16; P=.03), noninfectious inflammatory eruptions (NWH, 48; WH, 85; P<.001), and cutaneous drug eruptions (NWH, 5; WH, 27; P<.001) were reported in WH patients. There was no significant difference in benign vs malignant neoplastic processes between groups. More noninfectious inflammatory eruptions in WH were specifically driven by a markedly increased incidence of follicular (NWH, 9; WH, 29; P<.001) and urticarial/erythematous (NWH, 3; WH, 13; P=.02) lesions. Follicular etiologies included acne (NWH, 1; WH, 6; P=.12), folliculitis (NWH, 5; WH, 2; P=.45), hidradenitis suppurativa (NWH, 2; WH, 11; P=.02), and pilonidal and sebaceous cysts (NWH, 1; WH, 10; P=.01). Allergic urticaria dominated the urticarial/erythematous category (NWH, 3; WH, 11; P=.06), though there were 2 WH presentations of diffuse erythema and skin peeling.

Another substantial proportion of cutaneous etiologies were due to trauma or chronic wounds. Significantly more traumatic injuries presented in NWH patients vs WH patients (36 vs 31; P=.04). Trauma included human or dog bites (NWH, 5; WH, 4), sunburns (NWH, 3; WH, 0), other burns (NWH, 11; WH, 13), abrasions and lacerations (NWH, 16; WH, 3; P=.004), and foreign bodies (NWH, 1; WH, 1). Wounds consisted of chronic wounds such as those due to diabetes mellitus (foot ulcers) or immobility (sacral ulcers); numbers were similar between groups.

Looking at location, NWH patients had more pathology on the feet (NWH, 62; WH, 39; P=.02), whereas WH patients had more disseminated multiregional concerns (NWH, 55; WH, 75; P=.05). No one body location was notably more likely to warrant a chief concern.

For clinical outcomes, more WH patients received a consultation of any kind (NWH, 171; WH, 217; P<.001), consultation to dermatology (NWH, 49; WH, 87; P<.001), and consultation to surgery (NWH, 64; WH, 110; P<.001)(Table 3 and Figure). More outpatient referrals to dermatology were made for WH patients (NWH, 61; WH, 82; P=.05). Notably, NWH patients presented for 80% fewer hospital follow-up appointments (NWH, 11; WH, 55; P<.001). It is essential to note that these findings were not affected by self-reported race or ethnicity. Results remained significant when broken into cohorts consisting of patients with and without skin of color.

Comment

Cutaneous Concerns in NWH Patients—Although cutaneous disease has been reported to disproportionately affect NWH patients,¹⁰ in our cohort, NWH patients had fewer cutaneous chief concerns than WH patients. However, without comparing with all patients entering the ED at UMC, we cannot make a statement on this claim. We do present a few reasons why NWH patients do not have more cutaneous concerns. First, they may wait to present with cutaneous disease until it becomes more severe (eg, until chronic wounds have progressed to infections). Second, as discussed in depth by Hollestein and Nijsten,³ dermatologic disease may be a major contributor to the overall count of disability-adjusted life years but may play a minor role in individual disability. Therefore, skin disease often is considered less important on an individual basis, despite substantial psychosocial burden, leading to further stigmatization of this vulnerable population and discouraged care-seeking behavior, particularly for noninfectious inflammatory eruptions, which were notably more present in WH individuals. Third, fewer dermatologic lesions were reported on NWH patients, which may explain why all 3 WH pigmented lesions were diagnosed after presentation with a noncutaneous concern (eg, headache, anemia, nausea).

Infectious Cutaneous Diagnoses—The increased presentation of infectious etiologies, especially bacterial, is linked to the increased numbers of IVDUs reported in NWH individuals as well as increased exposure and decreased access to basic hygienic supplies. Intravenous drug use acted as an effect modifier of infectious etiology diagnoses, playing a major role in both NWH and WH cohorts. Although Black and Hispanic individuals as well as individuals with low socioeconomic status have increased proportions of skin cancer, there are inadequate data on the prevalence in NWH individuals.⁴ We found no increase in malignant dermatologic processes in NWH individuals; however, this may be secondary to inadequate screening with a total body skin examination.

Clinical Workup of NWH Patients—Because most NWH individuals present to the ED to receive care, their care compared with WH patients should be considered. In this cohort, WH patients received a less extensive clinical workup. They received almost half as many dermatologic consultations and fewer outpatient referrals to dermatology. Major communication barriers may affect NWH presentation to follow-up, which was drastically lower than WH individuals, as scheduling typically occurs well after discharge from the ED or inpatient unit. We suggest a few alterations to improve dermatologic care for NWH individuals:

• Consider inpatient consultation for serious dermatologic conditions—even if chronic—to improve disease control, considering that many barriers inhibit follow-up in clinic.

• Involve outreach teams, such as the Assertive Community Treatment teams, that assist individuals by delivering medicine for psychiatric disorders, conducting total-body skin examinations, assisting with wound care, providing basic skin barrier creams or medicaments, and carrying information regarding outpatient follow-up.

• Educate ED providers on the most common skin concerns, especially those that fall within the noninfectious inflammatory category, such as hidradenitis suppurativa, which could easily be misdiagnosed as an abscess.

Future Directions—Owing to limitations of a retrospective cohort study, we present several opportunities for further research on this vulnerable population. The severity of disease, especially infectious etiologies, should be graded to determine if NWH patients truly present later in the disease course. The duration and quality of housing for NWH patients could be categorized based on living conditions (eg, on the street vs in a shelter). Although the findings of our NWH cohort presenting to the ED at UMC provide helpful insight into dermatologic disease, these findings may be disparate from those conducted at other locations in the United States. University Medical Center provides care to mostly subsidized insurance plans in a racially diverse community. Improved outcomes for the NWH individuals living in New Orleans start with obtaining a greater understanding of their diseases and where disparities exist that can be bridged with better care.

Acknowledgment—The dataset generated during this study and used for analysis is not publicly available to protect public health information but is available from the corresponding author on reasonable request.

Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. ¹ Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). ¹ In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. ² Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. ¹ Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV. 

Case Report

A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.

During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.

After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion.  The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.

Comment

Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.³ Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.⁴ 

Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.⁵ Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.⁶ However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.

Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.⁶ Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.^1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.

Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.⁶ For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.

Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.⁶ Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.¹² Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).⁷ There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.^7-9

The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.

Conclusion

DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.

Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. ¹ Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). ¹ In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. ² Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. ¹ Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV. 

Case Report

A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.

During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.

After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion.  The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.

Comment

Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.³ Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.⁴ 

Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.⁵ Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.⁶ However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.

Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.⁶ Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.^1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.

Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.⁶ For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.

Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.⁶ Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.¹² Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).⁷ There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.^7-9

The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.

Conclusion

DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.

Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. ¹ Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). ¹ In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. ² Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. ¹ Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV. 

Case Report

A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.

During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.

After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion.  The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.

Comment

Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.³ Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.⁴ 

Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.⁵ Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.⁶ However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.

Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.⁶ Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.^1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.

Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.⁶ For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.

Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.⁶ Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.¹² Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).⁷ There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.^7-9

The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.

Conclusion

DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


A version of this article firsts appeared on WebMD.com.

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


A version of this article firsts appeared on WebMD.com.

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


A version of this article firsts appeared on WebMD.com.

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

A version of this article first appeared on Medscape.com.

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

A version of this article first appeared on Medscape.com.

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

A version of this article first appeared on Medscape.com.

U.S. regulators approved avacopan (Tavneos) for a rare immune disorder after receiving additional information to address concerns raised about the drug that were previously discussed at a public meeting in May.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

ChemoCentryx, the drug’s manufacturer, today announced that the U.S. Food and Drug Administration approved the drug as an adjunctive treatment for severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis).

This systemic disease results from overactivation of the complement system, leading to inflammation and eventual destruction of small blood vessels. This can lead to organ damage and failure, with the kidney as the major target, said the company in a statement.

The avacopan approval was based in large part on the results of the ADVOCATE trial, which were highlighted in a February 2021 editorial in the New England Journal of Medicine , titled “Avacopan – Time to replace glucocorticoids?” But the FDA-approved indication for avacopan is as an adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. “Tavneos does not eliminate glucocorticoid use,” the label states.

The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis conducted in 20 countries, ChemoCentryx said. Participants were randomly assigned to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone.

Subjects in both treatment groups could also receive nonprotocol glucocorticoids as needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS), ChemoCentryx said. Common adverse reactions among study participants included nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.

In the ChemoCentryx statement, Peter A. Merkel, MD, MPH, a consultant to the company and the chief of rheumatology at the University of Pennsylvania, Philadelphia, called the avacopan clearance a “first-in-a-decade approval of a medicine for ANCA-associated vasculitis.”

“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” Dr. Merkel said.

In reviewing the avacopan application, the FDA noted that the medicine is intended to treat “a rare and serious disease associated with high morbidity and increased mortality.”

“It is also a disease with high unmet need for new therapies,” the FDA staff said in a review of the ChemoCentryx application for approval of avacopan, which was posted online ahead of a meeting this past May.

Previous FDA concerns

In that review, FDA staff made public various concerns about the evidence used in seeking approval of the medicine. The FDA staff said there were “substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.”

Members of the FDA’s Arthritis Advisory Committee voted 10-8 on May 6 on a question of whether the risk-benefit profile of avacopan is adequate to support approval. The panel also voted 9-9 on whether the efficacy data support approval of avacopan, and 10-8 that the safety profile of avacopan is adequate to support approval.

ChemoCentryx in July said it filed an amendment to its new drug application (NDA) for avacopan. This appears to have answered regulators’ questions about the drug.

On a call with analysts Friday, ChemoCentryx officials outlined a marketing strategy for avacopan, with efforts focused on reaching influential rheumatologists and nephrologists. The company will set a U.S. wholesale acquisition cost for the drug of about $150,000-$200,000 a patient, in keeping with the range of prices often seen for orphan drugs. ChemoCentryx said it intends to offer financial support programs for the medicine.

ChemoCentryx said avacopan is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe is expected by the end of this year.

A version of this article first appeared on Medscape.com.

U.S. regulators approved avacopan (Tavneos) for a rare immune disorder after receiving additional information to address concerns raised about the drug that were previously discussed at a public meeting in May.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

ChemoCentryx, the drug’s manufacturer, today announced that the U.S. Food and Drug Administration approved the drug as an adjunctive treatment for severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis).

This systemic disease results from overactivation of the complement system, leading to inflammation and eventual destruction of small blood vessels. This can lead to organ damage and failure, with the kidney as the major target, said the company in a statement.

The avacopan approval was based in large part on the results of the ADVOCATE trial, which were highlighted in a February 2021 editorial in the New England Journal of Medicine , titled “Avacopan – Time to replace glucocorticoids?” But the FDA-approved indication for avacopan is as an adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. “Tavneos does not eliminate glucocorticoid use,” the label states.

The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis conducted in 20 countries, ChemoCentryx said. Participants were randomly assigned to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone.

Subjects in both treatment groups could also receive nonprotocol glucocorticoids as needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS), ChemoCentryx said. Common adverse reactions among study participants included nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.

In the ChemoCentryx statement, Peter A. Merkel, MD, MPH, a consultant to the company and the chief of rheumatology at the University of Pennsylvania, Philadelphia, called the avacopan clearance a “first-in-a-decade approval of a medicine for ANCA-associated vasculitis.”

“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” Dr. Merkel said.

In reviewing the avacopan application, the FDA noted that the medicine is intended to treat “a rare and serious disease associated with high morbidity and increased mortality.”

“It is also a disease with high unmet need for new therapies,” the FDA staff said in a review of the ChemoCentryx application for approval of avacopan, which was posted online ahead of a meeting this past May.

Previous FDA concerns

In that review, FDA staff made public various concerns about the evidence used in seeking approval of the medicine. The FDA staff said there were “substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.”

Members of the FDA’s Arthritis Advisory Committee voted 10-8 on May 6 on a question of whether the risk-benefit profile of avacopan is adequate to support approval. The panel also voted 9-9 on whether the efficacy data support approval of avacopan, and 10-8 that the safety profile of avacopan is adequate to support approval.

ChemoCentryx in July said it filed an amendment to its new drug application (NDA) for avacopan. This appears to have answered regulators’ questions about the drug.

On a call with analysts Friday, ChemoCentryx officials outlined a marketing strategy for avacopan, with efforts focused on reaching influential rheumatologists and nephrologists. The company will set a U.S. wholesale acquisition cost for the drug of about $150,000-$200,000 a patient, in keeping with the range of prices often seen for orphan drugs. ChemoCentryx said it intends to offer financial support programs for the medicine.

ChemoCentryx said avacopan is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe is expected by the end of this year.

A version of this article first appeared on Medscape.com.

U.S. regulators approved avacopan (Tavneos) for a rare immune disorder after receiving additional information to address concerns raised about the drug that were previously discussed at a public meeting in May.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

ChemoCentryx, the drug’s manufacturer, today announced that the U.S. Food and Drug Administration approved the drug as an adjunctive treatment for severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis).

This systemic disease results from overactivation of the complement system, leading to inflammation and eventual destruction of small blood vessels. This can lead to organ damage and failure, with the kidney as the major target, said the company in a statement.

The avacopan approval was based in large part on the results of the ADVOCATE trial, which were highlighted in a February 2021 editorial in the New England Journal of Medicine , titled “Avacopan – Time to replace glucocorticoids?” But the FDA-approved indication for avacopan is as an adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. “Tavneos does not eliminate glucocorticoid use,” the label states.

The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis conducted in 20 countries, ChemoCentryx said. Participants were randomly assigned to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone.

Subjects in both treatment groups could also receive nonprotocol glucocorticoids as needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS), ChemoCentryx said. Common adverse reactions among study participants included nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.

In the ChemoCentryx statement, Peter A. Merkel, MD, MPH, a consultant to the company and the chief of rheumatology at the University of Pennsylvania, Philadelphia, called the avacopan clearance a “first-in-a-decade approval of a medicine for ANCA-associated vasculitis.”

“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” Dr. Merkel said.

In reviewing the avacopan application, the FDA noted that the medicine is intended to treat “a rare and serious disease associated with high morbidity and increased mortality.”

“It is also a disease with high unmet need for new therapies,” the FDA staff said in a review of the ChemoCentryx application for approval of avacopan, which was posted online ahead of a meeting this past May.

Previous FDA concerns

In that review, FDA staff made public various concerns about the evidence used in seeking approval of the medicine. The FDA staff said there were “substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.”

Members of the FDA’s Arthritis Advisory Committee voted 10-8 on May 6 on a question of whether the risk-benefit profile of avacopan is adequate to support approval. The panel also voted 9-9 on whether the efficacy data support approval of avacopan, and 10-8 that the safety profile of avacopan is adequate to support approval.

ChemoCentryx in July said it filed an amendment to its new drug application (NDA) for avacopan. This appears to have answered regulators’ questions about the drug.

On a call with analysts Friday, ChemoCentryx officials outlined a marketing strategy for avacopan, with efforts focused on reaching influential rheumatologists and nephrologists. The company will set a U.S. wholesale acquisition cost for the drug of about $150,000-$200,000 a patient, in keeping with the range of prices often seen for orphan drugs. ChemoCentryx said it intends to offer financial support programs for the medicine.

ChemoCentryx said avacopan is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe is expected by the end of this year.

A version of this article first appeared on Medscape.com.