Cutis

To the Editor:

Alopecia areata (AA), an autoimmune disease characterized by inflammatory and nonscarring hair loss, can have a considerable impact on quality of life.¹ Baricitinib is a Janus kinase inhibitor that recently was approved by the US Food and Drug Administration for treatment of severe AA in adult patients, becoming the only on-label treatment available.² So far, the most common adverse effects reported in phase 3 trials have been acne, upper respiratory tract infections, headaches, urinary tract infections, and elevated creatine kinase levels.³

At our trichology unit in the dermatology department of a Spanish tertiary-care hospital in Seville, we have successfully used baricitinib to treat 18 patients with severe, therapy-resistant AA. Herein, we present a case of trichilemmal cyst reactivation in one of our patients following successful treatment with baricitinib.

A 53-year-old woman with a history of trichilemmal cysts presented to the dermatology department with total body hair loss of 5 years' duration that was diagnosed as AA universalis (Figure, A). The patient reported that the trichilemmal cysts had shrunk drastically 1 month after complete loss of body hair (Severity of Alopecia Tool [SALT] score, 100)(Figure, B). The largest cyst was surgically removed, and the diagnosis was histologically confirmed by a pathologist. Her mother and sister also had a history of multiple trichilemmal cysts.

The patient previously had failed treatment with oral prednisone 50 mg/d, oral cyclosporine 4 mg/kg/d, oral dexamethasone 4 mg twice weekly, and oral azathioprine 300 mg/wk. Due to the new indication of baricitinib for AA, we opted to start the patient on oral baricitinib 4 mg/d. By week 8 of treatment, she had achieved total hair regrowth (SALT score, 0). This rapid response might indicate a quick-responder phenotype, referring to a subset of patients who exhibit a fast and robust response to treatment (SALT90), generally before week 16, although more evidence is needed.

Notably, we observed the reactivation of 4 trichilemmal cysts on the scalp 6 weeks after starting baricitinib. To our knowledge, this side effect has not previously been reported. We hypothesize that reactivation of the cysts may have been due to the inhibition of the Janus kinase/signal transducer and activator of transcription pathway, which reduces the effects of cytokines and leads to reactivation of hair follicles that were inactive because of inflammation.⁴ As a result, the outer root sheath of the hair follicle can once again be filled with keratin, thereby reactivating the trichilemmal cysts. Based on our experience with this case, it may be relevant to consider personal and family history of trichilemmal cysts before starting treatment with baricitinib for AA and advise the patient about the possibility of this adverse effect.

To the Editor:

Alopecia areata (AA), an autoimmune disease characterized by inflammatory and nonscarring hair loss, can have a considerable impact on quality of life.¹ Baricitinib is a Janus kinase inhibitor that recently was approved by the US Food and Drug Administration for treatment of severe AA in adult patients, becoming the only on-label treatment available.² So far, the most common adverse effects reported in phase 3 trials have been acne, upper respiratory tract infections, headaches, urinary tract infections, and elevated creatine kinase levels.³

At our trichology unit in the dermatology department of a Spanish tertiary-care hospital in Seville, we have successfully used baricitinib to treat 18 patients with severe, therapy-resistant AA. Herein, we present a case of trichilemmal cyst reactivation in one of our patients following successful treatment with baricitinib.

A 53-year-old woman with a history of trichilemmal cysts presented to the dermatology department with total body hair loss of 5 years' duration that was diagnosed as AA universalis (Figure, A). The patient reported that the trichilemmal cysts had shrunk drastically 1 month after complete loss of body hair (Severity of Alopecia Tool [SALT] score, 100)(Figure, B). The largest cyst was surgically removed, and the diagnosis was histologically confirmed by a pathologist. Her mother and sister also had a history of multiple trichilemmal cysts.

The patient previously had failed treatment with oral prednisone 50 mg/d, oral cyclosporine 4 mg/kg/d, oral dexamethasone 4 mg twice weekly, and oral azathioprine 300 mg/wk. Due to the new indication of baricitinib for AA, we opted to start the patient on oral baricitinib 4 mg/d. By week 8 of treatment, she had achieved total hair regrowth (SALT score, 0). This rapid response might indicate a quick-responder phenotype, referring to a subset of patients who exhibit a fast and robust response to treatment (SALT90), generally before week 16, although more evidence is needed.

Notably, we observed the reactivation of 4 trichilemmal cysts on the scalp 6 weeks after starting baricitinib. To our knowledge, this side effect has not previously been reported. We hypothesize that reactivation of the cysts may have been due to the inhibition of the Janus kinase/signal transducer and activator of transcription pathway, which reduces the effects of cytokines and leads to reactivation of hair follicles that were inactive because of inflammation.⁴ As a result, the outer root sheath of the hair follicle can once again be filled with keratin, thereby reactivating the trichilemmal cysts. Based on our experience with this case, it may be relevant to consider personal and family history of trichilemmal cysts before starting treatment with baricitinib for AA and advise the patient about the possibility of this adverse effect.

To the Editor:

Alopecia areata (AA), an autoimmune disease characterized by inflammatory and nonscarring hair loss, can have a considerable impact on quality of life.¹ Baricitinib is a Janus kinase inhibitor that recently was approved by the US Food and Drug Administration for treatment of severe AA in adult patients, becoming the only on-label treatment available.² So far, the most common adverse effects reported in phase 3 trials have been acne, upper respiratory tract infections, headaches, urinary tract infections, and elevated creatine kinase levels.³

At our trichology unit in the dermatology department of a Spanish tertiary-care hospital in Seville, we have successfully used baricitinib to treat 18 patients with severe, therapy-resistant AA. Herein, we present a case of trichilemmal cyst reactivation in one of our patients following successful treatment with baricitinib.

A 53-year-old woman with a history of trichilemmal cysts presented to the dermatology department with total body hair loss of 5 years' duration that was diagnosed as AA universalis (Figure, A). The patient reported that the trichilemmal cysts had shrunk drastically 1 month after complete loss of body hair (Severity of Alopecia Tool [SALT] score, 100)(Figure, B). The largest cyst was surgically removed, and the diagnosis was histologically confirmed by a pathologist. Her mother and sister also had a history of multiple trichilemmal cysts.

The patient previously had failed treatment with oral prednisone 50 mg/d, oral cyclosporine 4 mg/kg/d, oral dexamethasone 4 mg twice weekly, and oral azathioprine 300 mg/wk. Due to the new indication of baricitinib for AA, we opted to start the patient on oral baricitinib 4 mg/d. By week 8 of treatment, she had achieved total hair regrowth (SALT score, 0). This rapid response might indicate a quick-responder phenotype, referring to a subset of patients who exhibit a fast and robust response to treatment (SALT90), generally before week 16, although more evidence is needed.

Notably, we observed the reactivation of 4 trichilemmal cysts on the scalp 6 weeks after starting baricitinib. To our knowledge, this side effect has not previously been reported. We hypothesize that reactivation of the cysts may have been due to the inhibition of the Janus kinase/signal transducer and activator of transcription pathway, which reduces the effects of cytokines and leads to reactivation of hair follicles that were inactive because of inflammation.⁴ As a result, the outer root sheath of the hair follicle can once again be filled with keratin, thereby reactivating the trichilemmal cysts. Based on our experience with this case, it may be relevant to consider personal and family history of trichilemmal cysts before starting treatment with baricitinib for AA and advise the patient about the possibility of this adverse effect.

Most medical students applying to dermatology residency programs in the United States will participate in an away rotation at an outside institution. Prior to COVID-19–related restrictions, 86.7% of dermatology applicants from the class of 2020 reported completing one or more away rotations for their application cycle.^1,2 This requirement can be considerably costly, especially since most programs do not offer financial support for travel, living expenses, or housing during these visiting experiences.³ Underrepresented in medicine (URiM) students may be particularly disadvantaged with regard to the financial obligations that come with away rotations.^4,5 Visiting scholarships for URiM students can mitigate these challenges, creating opportunities for increasing diversity in dermatology. When medical students begin the residency application process, the Visiting Student Learning Opportunities (VSLO) program of the Association of American Medical Colleges (AAMC) is the most widely used third-party service for submitting applications. For many URiM students, an unforeseen challenge when applying to dermatology residency programs is the lack of an easily accessible and up-to-date search tool to find programs that offer funding, resulting in more time spent searching and thereby complicating the application process. The VSLO released the Visiting Scholars Resources Database, a search tool that aims to compile opportunities for additional support—academic professional, and/or financial—to address this issue. Additionally, the Funded Away Rotations for Minority Medical Students (FARMS) database is an independent directory of programs that offer stipends to URiM students. In this study, we evaluated the efficacy of the VLSO’s Visiting Scholars Resources Database search tool and the FARMS database in identifying funded dermatology rotations for URiM students.

Overview of Online Search Tools

We used the AAMC’s Electronic Residency Application Service Directory to identify 141 programs offering dermatology residency positions. We then conducted a Google search using each program name with the phrase underrepresented in medicine dermatology away rotation to identify any opportunities noted in the Google results offering scholarship funding for URiM students. If there were no Google results for a webpage discussing URiM away rotation opportunities for a certain program, the individual program’s website search box was queried using the terms URiM, scholarship, and funding. If there were no relevant results, the webpages associated with the dermatology department, away rotations, and diversity and inclusion on the respective institution’s website were reviewed to confirm no indication of funded URiM opportunities. Of the 141 dermatology programs we evaluated, we identified 56 (39.7%) that offered funded away rotations for URiM students.

For comparison, we conducted a search of the VSLO’s Visiting Scholars Resources Database to identify programs that listed dermatology, all (specialties), or any (specialties) under the Specialty column that also had a financial resource for URiM students. Our search of the VSLO database yielded only 12 (21.4%) of the 56 funded away rotations we identified via our initial Google and program website search. Program listings tagged for dermatology also were retrieved from the FARMS database, of which only 17 (30.4%) of the 56 funded away rotations we previously identified were included. All queries were performed from October 24 to October 26, 2024 (Figure).

Comment

The 2023-2024 AAMC Report on Residents indicated that 54.9% (800/1455) of active US dermatology medical residents identified as White, 27.5% (400/1455) identified as Asian, 8.9% (129/1455) identified as Hispanic, and 8.7% (126/1455) identified as Black or African American.⁶ By comparison, 19.5% of the general US population identifies as Hispanic and 13.7% identifies as Black.⁷ Within the field of dermatology, the proportion of Black dermatology academic faculty in the US is estimated to comprise only 18.7% of all active Black dermatologists.^8,9 With a growing population of minority US citizens, the dermatology workforce is lagging in representation across all minority populations, especially when it comes to Hispanic and Black individuals. To increase the diversity of the US dermatology workforce, residency programs must prioritize recruitment of URiM students and support their retention as future faculty.

Reports in the literature suggest that clinical grades, US Medical Licensing Examination scores, letters of recommendation/ networking, and the risk of not matching are among the primary concerns that URiM students face as potential barriers to applying for dermatology residency.⁴ Meanwhile, dermatology program directors ranked diversity characteristics, perceived interest in the program, personal prior knowledge of an applicant, and audition rotation in their department as important considerations for interviewing applicants.¹⁰ As a result, URiM students may have the diverse characteristics that program directors are looking for, but obtaining away rotations and establishing mentors at other institutions may be challenging due to the burden of accruing additional costs for visiting rotations.^2,10,11 Other reports have indicated that expanding funded dermatology visiting rotations and promoting national programs such as the American Academy of Dermatology Diversity Mentorship Program (https://www.aad.org/member/career/awards/diversity) or the Skin of Color Society Observership Grant (https://skinofcolorsociety.org/what-we-do/mentorship/observership-grant) can be alternative routes for mentorship and networking.³

Our review demonstrated that, of the 141 dermatology residency programs we identified, only around 40% offer funded rotations for URiM students; however, the current databases that applicants use to find these opportunities do not adequately present the number of available options. A search of the VSLO database—the most widely used third-party database for applying to dermatology away rotations—yielded only 12 (21.4%) of the rotations that we identified in our initial Google search. Similarly, a search of the FARMS database yielded only 17 (30.4%) of the dermatology rotations we previously identified. Aside from missing more than half of the available funded dermatology away rotations, the search process was further complicated by the reliance of the 2 databases on user input rather than presenting all programs offering funded opportunities for dermatology applicants without the need to enter additional information. As of October 26, 2024, there were only 22 inputs for Visiting Scholars Resources across all specialties and programs in the VLSO system.

Our findings indicate a clear need for a reliable and accurate database that captures all funded dermatology rotations for prospective URiM applicants because of the strong emphasis on visiting rotations for application success. Our team created a Google spreadsheet compiling dermatology visiting student health equity and inclusion scholarships from inputs we found in our search. We shared this resource via the Association of Professors of Dermatology listserve so program members could verify the opportunities we compiled to create an accurate and updated resource for finding funded dermatology rotations. The program verification process was conducted by having residency program directors or their respective program coordinators mark “yes” on the spreadsheet to confirm the funded rotation is being offered by their program. Our spreadsheet will continue to be updated yearly through cooperation with participating programs to verify their funded electives and through partnership with the AAMC to include our database in their Visiting Students Resources Database that will be released each year within VLSO as applications open for the following season.

The main limitation of our review is that we presume the information provided in the VSLO and FARMS databases has not changed or been updated to include more programs since our initial search period. Additionally, the information available on dermatology residency program websites limits the data on the total programs obtained, as some website links may not be updated or may be invalid for online web user access. The benefit to creating and continually updating our Dermatology Visiting Student Health Equity and Inclusion Scholarship Database spreadsheet will be to ensure that programs regularly verify their offered funded electives and capture the true total of funded rotations offered for URiM students across the country. We also acknowledge that we did not investigate how URiM student attendance at funded rotations affected their outcomes in matching dermatology programs for residency; however, given the importance of away rotations, which positively influence the ability of URiM students to receive interviews, it is understood that these opportunities are viewed as widely beneficial.

Final Thoughts

The current online search tools that URiM students can use to find funded away rotations in dermatology exclude many of the available opportunities. We aimed to provide an updated and centralized resource for students via the shared spreadsheet we created for residency program directors, but further measures to centralize the most up-to-date information on visiting programs offering scholarships to URiM students would be beneficial.

Most medical students applying to dermatology residency programs in the United States will participate in an away rotation at an outside institution. Prior to COVID-19–related restrictions, 86.7% of dermatology applicants from the class of 2020 reported completing one or more away rotations for their application cycle.^1,2 This requirement can be considerably costly, especially since most programs do not offer financial support for travel, living expenses, or housing during these visiting experiences.³ Underrepresented in medicine (URiM) students may be particularly disadvantaged with regard to the financial obligations that come with away rotations.^4,5 Visiting scholarships for URiM students can mitigate these challenges, creating opportunities for increasing diversity in dermatology. When medical students begin the residency application process, the Visiting Student Learning Opportunities (VSLO) program of the Association of American Medical Colleges (AAMC) is the most widely used third-party service for submitting applications. For many URiM students, an unforeseen challenge when applying to dermatology residency programs is the lack of an easily accessible and up-to-date search tool to find programs that offer funding, resulting in more time spent searching and thereby complicating the application process. The VSLO released the Visiting Scholars Resources Database, a search tool that aims to compile opportunities for additional support—academic professional, and/or financial—to address this issue. Additionally, the Funded Away Rotations for Minority Medical Students (FARMS) database is an independent directory of programs that offer stipends to URiM students. In this study, we evaluated the efficacy of the VLSO’s Visiting Scholars Resources Database search tool and the FARMS database in identifying funded dermatology rotations for URiM students.

Overview of Online Search Tools

We used the AAMC’s Electronic Residency Application Service Directory to identify 141 programs offering dermatology residency positions. We then conducted a Google search using each program name with the phrase underrepresented in medicine dermatology away rotation to identify any opportunities noted in the Google results offering scholarship funding for URiM students. If there were no Google results for a webpage discussing URiM away rotation opportunities for a certain program, the individual program’s website search box was queried using the terms URiM, scholarship, and funding. If there were no relevant results, the webpages associated with the dermatology department, away rotations, and diversity and inclusion on the respective institution’s website were reviewed to confirm no indication of funded URiM opportunities. Of the 141 dermatology programs we evaluated, we identified 56 (39.7%) that offered funded away rotations for URiM students.

For comparison, we conducted a search of the VSLO’s Visiting Scholars Resources Database to identify programs that listed dermatology, all (specialties), or any (specialties) under the Specialty column that also had a financial resource for URiM students. Our search of the VSLO database yielded only 12 (21.4%) of the 56 funded away rotations we identified via our initial Google and program website search. Program listings tagged for dermatology also were retrieved from the FARMS database, of which only 17 (30.4%) of the 56 funded away rotations we previously identified were included. All queries were performed from October 24 to October 26, 2024 (Figure).

Comment

The 2023-2024 AAMC Report on Residents indicated that 54.9% (800/1455) of active US dermatology medical residents identified as White, 27.5% (400/1455) identified as Asian, 8.9% (129/1455) identified as Hispanic, and 8.7% (126/1455) identified as Black or African American.⁶ By comparison, 19.5% of the general US population identifies as Hispanic and 13.7% identifies as Black.⁷ Within the field of dermatology, the proportion of Black dermatology academic faculty in the US is estimated to comprise only 18.7% of all active Black dermatologists.^8,9 With a growing population of minority US citizens, the dermatology workforce is lagging in representation across all minority populations, especially when it comes to Hispanic and Black individuals. To increase the diversity of the US dermatology workforce, residency programs must prioritize recruitment of URiM students and support their retention as future faculty.

Reports in the literature suggest that clinical grades, US Medical Licensing Examination scores, letters of recommendation/ networking, and the risk of not matching are among the primary concerns that URiM students face as potential barriers to applying for dermatology residency.⁴ Meanwhile, dermatology program directors ranked diversity characteristics, perceived interest in the program, personal prior knowledge of an applicant, and audition rotation in their department as important considerations for interviewing applicants.¹⁰ As a result, URiM students may have the diverse characteristics that program directors are looking for, but obtaining away rotations and establishing mentors at other institutions may be challenging due to the burden of accruing additional costs for visiting rotations.^2,10,11 Other reports have indicated that expanding funded dermatology visiting rotations and promoting national programs such as the American Academy of Dermatology Diversity Mentorship Program (https://www.aad.org/member/career/awards/diversity) or the Skin of Color Society Observership Grant (https://skinofcolorsociety.org/what-we-do/mentorship/observership-grant) can be alternative routes for mentorship and networking.³

Our review demonstrated that, of the 141 dermatology residency programs we identified, only around 40% offer funded rotations for URiM students; however, the current databases that applicants use to find these opportunities do not adequately present the number of available options. A search of the VSLO database—the most widely used third-party database for applying to dermatology away rotations—yielded only 12 (21.4%) of the rotations that we identified in our initial Google search. Similarly, a search of the FARMS database yielded only 17 (30.4%) of the dermatology rotations we previously identified. Aside from missing more than half of the available funded dermatology away rotations, the search process was further complicated by the reliance of the 2 databases on user input rather than presenting all programs offering funded opportunities for dermatology applicants without the need to enter additional information. As of October 26, 2024, there were only 22 inputs for Visiting Scholars Resources across all specialties and programs in the VLSO system.

Our findings indicate a clear need for a reliable and accurate database that captures all funded dermatology rotations for prospective URiM applicants because of the strong emphasis on visiting rotations for application success. Our team created a Google spreadsheet compiling dermatology visiting student health equity and inclusion scholarships from inputs we found in our search. We shared this resource via the Association of Professors of Dermatology listserve so program members could verify the opportunities we compiled to create an accurate and updated resource for finding funded dermatology rotations. The program verification process was conducted by having residency program directors or their respective program coordinators mark “yes” on the spreadsheet to confirm the funded rotation is being offered by their program. Our spreadsheet will continue to be updated yearly through cooperation with participating programs to verify their funded electives and through partnership with the AAMC to include our database in their Visiting Students Resources Database that will be released each year within VLSO as applications open for the following season.

The main limitation of our review is that we presume the information provided in the VSLO and FARMS databases has not changed or been updated to include more programs since our initial search period. Additionally, the information available on dermatology residency program websites limits the data on the total programs obtained, as some website links may not be updated or may be invalid for online web user access. The benefit to creating and continually updating our Dermatology Visiting Student Health Equity and Inclusion Scholarship Database spreadsheet will be to ensure that programs regularly verify their offered funded electives and capture the true total of funded rotations offered for URiM students across the country. We also acknowledge that we did not investigate how URiM student attendance at funded rotations affected their outcomes in matching dermatology programs for residency; however, given the importance of away rotations, which positively influence the ability of URiM students to receive interviews, it is understood that these opportunities are viewed as widely beneficial.

Final Thoughts

The current online search tools that URiM students can use to find funded away rotations in dermatology exclude many of the available opportunities. We aimed to provide an updated and centralized resource for students via the shared spreadsheet we created for residency program directors, but further measures to centralize the most up-to-date information on visiting programs offering scholarships to URiM students would be beneficial.

Most medical students applying to dermatology residency programs in the United States will participate in an away rotation at an outside institution. Prior to COVID-19–related restrictions, 86.7% of dermatology applicants from the class of 2020 reported completing one or more away rotations for their application cycle.^1,2 This requirement can be considerably costly, especially since most programs do not offer financial support for travel, living expenses, or housing during these visiting experiences.³ Underrepresented in medicine (URiM) students may be particularly disadvantaged with regard to the financial obligations that come with away rotations.^4,5 Visiting scholarships for URiM students can mitigate these challenges, creating opportunities for increasing diversity in dermatology. When medical students begin the residency application process, the Visiting Student Learning Opportunities (VSLO) program of the Association of American Medical Colleges (AAMC) is the most widely used third-party service for submitting applications. For many URiM students, an unforeseen challenge when applying to dermatology residency programs is the lack of an easily accessible and up-to-date search tool to find programs that offer funding, resulting in more time spent searching and thereby complicating the application process. The VSLO released the Visiting Scholars Resources Database, a search tool that aims to compile opportunities for additional support—academic professional, and/or financial—to address this issue. Additionally, the Funded Away Rotations for Minority Medical Students (FARMS) database is an independent directory of programs that offer stipends to URiM students. In this study, we evaluated the efficacy of the VLSO’s Visiting Scholars Resources Database search tool and the FARMS database in identifying funded dermatology rotations for URiM students.

Overview of Online Search Tools

We used the AAMC’s Electronic Residency Application Service Directory to identify 141 programs offering dermatology residency positions. We then conducted a Google search using each program name with the phrase underrepresented in medicine dermatology away rotation to identify any opportunities noted in the Google results offering scholarship funding for URiM students. If there were no Google results for a webpage discussing URiM away rotation opportunities for a certain program, the individual program’s website search box was queried using the terms URiM, scholarship, and funding. If there were no relevant results, the webpages associated with the dermatology department, away rotations, and diversity and inclusion on the respective institution’s website were reviewed to confirm no indication of funded URiM opportunities. Of the 141 dermatology programs we evaluated, we identified 56 (39.7%) that offered funded away rotations for URiM students.

For comparison, we conducted a search of the VSLO’s Visiting Scholars Resources Database to identify programs that listed dermatology, all (specialties), or any (specialties) under the Specialty column that also had a financial resource for URiM students. Our search of the VSLO database yielded only 12 (21.4%) of the 56 funded away rotations we identified via our initial Google and program website search. Program listings tagged for dermatology also were retrieved from the FARMS database, of which only 17 (30.4%) of the 56 funded away rotations we previously identified were included. All queries were performed from October 24 to October 26, 2024 (Figure).

Comment

The 2023-2024 AAMC Report on Residents indicated that 54.9% (800/1455) of active US dermatology medical residents identified as White, 27.5% (400/1455) identified as Asian, 8.9% (129/1455) identified as Hispanic, and 8.7% (126/1455) identified as Black or African American.⁶ By comparison, 19.5% of the general US population identifies as Hispanic and 13.7% identifies as Black.⁷ Within the field of dermatology, the proportion of Black dermatology academic faculty in the US is estimated to comprise only 18.7% of all active Black dermatologists.^8,9 With a growing population of minority US citizens, the dermatology workforce is lagging in representation across all minority populations, especially when it comes to Hispanic and Black individuals. To increase the diversity of the US dermatology workforce, residency programs must prioritize recruitment of URiM students and support their retention as future faculty.

Reports in the literature suggest that clinical grades, US Medical Licensing Examination scores, letters of recommendation/ networking, and the risk of not matching are among the primary concerns that URiM students face as potential barriers to applying for dermatology residency.⁴ Meanwhile, dermatology program directors ranked diversity characteristics, perceived interest in the program, personal prior knowledge of an applicant, and audition rotation in their department as important considerations for interviewing applicants.¹⁰ As a result, URiM students may have the diverse characteristics that program directors are looking for, but obtaining away rotations and establishing mentors at other institutions may be challenging due to the burden of accruing additional costs for visiting rotations.^2,10,11 Other reports have indicated that expanding funded dermatology visiting rotations and promoting national programs such as the American Academy of Dermatology Diversity Mentorship Program (https://www.aad.org/member/career/awards/diversity) or the Skin of Color Society Observership Grant (https://skinofcolorsociety.org/what-we-do/mentorship/observership-grant) can be alternative routes for mentorship and networking.³

Our review demonstrated that, of the 141 dermatology residency programs we identified, only around 40% offer funded rotations for URiM students; however, the current databases that applicants use to find these opportunities do not adequately present the number of available options. A search of the VSLO database—the most widely used third-party database for applying to dermatology away rotations—yielded only 12 (21.4%) of the rotations that we identified in our initial Google search. Similarly, a search of the FARMS database yielded only 17 (30.4%) of the dermatology rotations we previously identified. Aside from missing more than half of the available funded dermatology away rotations, the search process was further complicated by the reliance of the 2 databases on user input rather than presenting all programs offering funded opportunities for dermatology applicants without the need to enter additional information. As of October 26, 2024, there were only 22 inputs for Visiting Scholars Resources across all specialties and programs in the VLSO system.

Our findings indicate a clear need for a reliable and accurate database that captures all funded dermatology rotations for prospective URiM applicants because of the strong emphasis on visiting rotations for application success. Our team created a Google spreadsheet compiling dermatology visiting student health equity and inclusion scholarships from inputs we found in our search. We shared this resource via the Association of Professors of Dermatology listserve so program members could verify the opportunities we compiled to create an accurate and updated resource for finding funded dermatology rotations. The program verification process was conducted by having residency program directors or their respective program coordinators mark “yes” on the spreadsheet to confirm the funded rotation is being offered by their program. Our spreadsheet will continue to be updated yearly through cooperation with participating programs to verify their funded electives and through partnership with the AAMC to include our database in their Visiting Students Resources Database that will be released each year within VLSO as applications open for the following season.

The main limitation of our review is that we presume the information provided in the VSLO and FARMS databases has not changed or been updated to include more programs since our initial search period. Additionally, the information available on dermatology residency program websites limits the data on the total programs obtained, as some website links may not be updated or may be invalid for online web user access. The benefit to creating and continually updating our Dermatology Visiting Student Health Equity and Inclusion Scholarship Database spreadsheet will be to ensure that programs regularly verify their offered funded electives and capture the true total of funded rotations offered for URiM students across the country. We also acknowledge that we did not investigate how URiM student attendance at funded rotations affected their outcomes in matching dermatology programs for residency; however, given the importance of away rotations, which positively influence the ability of URiM students to receive interviews, it is understood that these opportunities are viewed as widely beneficial.

Final Thoughts

The current online search tools that URiM students can use to find funded away rotations in dermatology exclude many of the available opportunities. We aimed to provide an updated and centralized resource for students via the shared spreadsheet we created for residency program directors, but further measures to centralize the most up-to-date information on visiting programs offering scholarships to URiM students would be beneficial.

THE DIAGNOSIS: Plaquelike Myofibroblastic Tumor

An incisional biopsy of the plaque demonstrated a hypercellular proliferation of bland spindle cells in the dermis that infiltrated the subcutis. The overlying epidermis was mildly acanthotic with both ulceration and follicular induction. There was trapping of individual adipocytes in a honeycomb pattern with foci of erythrocyte extravasation, microvesiculation, and widened fibrous septa (Figure 1). Immunohistochemistry was positive for vimentin, actin, and smooth muscle actin (SMA)(Figure 2A). Variable positivity for Factor XIIIa antibodies was noted. CD68 staining was focal positive, suggesting fibrohistiocytic lineage. Expression of CD31, CD34, S100, and anaplastic lymphoma kinase was negative, and Ki-67 was present in less than 10% of cells (Figure 2B).

We reviewed the case in conjunction with a soft-tissue pathologist (Y.L.), and based on the clinical and immunophenotypic features, a diagnosis of plaquelike myofibroblastic tumor (PLMT) was made. The patient’s parents refused further treatment, and there was no sign of disease progression at 6-month follow-up.

Plaquelike myofibroblastic tumor is an unusual pediatric dermal tumor that was first described by Clarke et al¹ in 2007. Clinical manifestation of PLMT on the right abdomen was unique in our patient, as the lesions typically present as indurated plaques on the lower back, but the central ulceration in our case resembled a report by Marqueling et al.² Ulceration and induration of PLMT developing at 8 months of age can suggest an aggressive disease course corresponding with deep infiltration and is seen mostly in children.

The histopathologic features of PLMT include an acanthotic epidermis and follicular induction, which also are characteristic of dermatofibroma (DF). The proliferation of spindle cells extended deep into the fat with foci of erythrocyte extravasation and microvesiculation of the stroma similar to nodular fasciitis and proliferative fasciitis. The presentation of infiltrating and expanding fibrous septae and trapping of individual adipocytes in a honeycomb pattern is similar to dermatofibrosarcoma protuberans (DFSP). Most cases of PLMT are positive for SMA. Factor XIIIa typically is variably positive, and in one report, 31% (4/13) of cases showed positive staining for calponin.³ Rapid growth, ulceration, and recurrence emphasize that PLMT can be locally aggressive, similar to DFSP.⁴

The main differential diagnoses include DF and its variants, dermatomyofibroma, DFSP, and proliferative fasciitis.^3,5 In the cases mentioned above, microscopic features were similar with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles through the entire reticular dermis, and the overlying epidermis was acanthotic.

Dermatofibroma commonly manifests in adults as a minor nodular lesion (commonly <1 cm), and usually is located on the legs. It has several clinical and histologic variants, including multiple clustered DF (MCDF)—a rare condition that has been reported in children and young adults and generally appears in the first and second decades of life. Of the reported cases of MCDF, immunohistochemical staining for SMA was performed in 8 cases. All these cases showed negative or minimal staining.^3-5 Smooth muscle actin staining in DFs is negative, or weak and patchy, unlike in PLMT where it is diffuse, uniform, and strong.

Dermatofibrosarcoma protuberans typically occurs in young adults and manifests as dermal and subcutaneous nodular/multinodular or plaquelike masses, with rare congenital cases. Immunohistochemical staining for CD34, which typically is firmly and diffusely positive, is the most reliable marker of DFSP.⁶ Factor XIIIA in DFSP typically is negative for focal staining, mainly at periphery or in scattered dendritic cells. The prognosis of DFSP generally is excellent, with local recurrences in up to 30% of cases and extremely low metastatic potential (essentially only in cases with fibrosarcomatous transformation).⁶ Dermatomyofibroma is another rare benign dermal myofibroblastic tumor that typically manifests with indurated hyperpigmented or erythematous plaques or nodules on the shoulders and torso.⁶ This condition occurs mainly in adolescents and young adults, unlike PLMT. The most striking features of dermatomyofibroma are the horizontal orientation of the spindle cell nuclei and the pattern of the proliferation concerning the adnexal structures, especially hair follicles. The hair follicles have a normal appearance, and the proliferation extends up to each follicle, then continues to the other side without any displacement of the follicle. Tumor cells are variably positive for SMA in dermatomyofibromas and are negative for muscle-specific actin, desmin, S100, CD34, and Factor XIIIA.⁶

Immunohistochemistry can be very useful in differentiating PLMT from other conditions. Neoplastic cells stain positively for CD34 but not for Factor XIIIa and SMA in cases of DFSP. Dermatofibroma and its variants always present with collagen trapping at the periphery of the lesions and may demonstrate foamy macrophages, hemosiderin, or plasma cells FXIIIA(+), CD34(-), and variable SMA reactivity. This positivity usually is less prominent in DF than in PLMT. Neoplastic cells in dermatomyofibroma often stain positive for calponin, but only focally for SMA. The clinical features of dermatomyofibroma include early onset, large size, multiple nodules, and plaquelike morphology. Moulonguet et al⁴ hypothesized that, although MCDF and PLMT appear to show some distinctive clinical and histologic features, they also show similarities that could suggest they form part of the myofibroblastic spectrum. Furthermore, Moradi et al⁷ also considered them as part of the same disease spectrum because of their overlapping clinical, histologic, and immunohistochemical features.

The microscopic features in our case are notable, as the lesion demonstrated overlying acanthosis and follicular induction, resembling DF. The stroma contained microvesicular changes and erythrocyte extravasation, characteristic of nodular or proliferative fasciitis. Additionally, densely packed spindle cells infiltrated deep into the subcutaneous adipose tissue, similar to DFSP.^2,3 Our findings expand on the reported histopathologic spectrum of this tumor to date.

THE DIAGNOSIS: Plaquelike Myofibroblastic Tumor

An incisional biopsy of the plaque demonstrated a hypercellular proliferation of bland spindle cells in the dermis that infiltrated the subcutis. The overlying epidermis was mildly acanthotic with both ulceration and follicular induction. There was trapping of individual adipocytes in a honeycomb pattern with foci of erythrocyte extravasation, microvesiculation, and widened fibrous septa (Figure 1). Immunohistochemistry was positive for vimentin, actin, and smooth muscle actin (SMA)(Figure 2A). Variable positivity for Factor XIIIa antibodies was noted. CD68 staining was focal positive, suggesting fibrohistiocytic lineage. Expression of CD31, CD34, S100, and anaplastic lymphoma kinase was negative, and Ki-67 was present in less than 10% of cells (Figure 2B).

We reviewed the case in conjunction with a soft-tissue pathologist (Y.L.), and based on the clinical and immunophenotypic features, a diagnosis of plaquelike myofibroblastic tumor (PLMT) was made. The patient’s parents refused further treatment, and there was no sign of disease progression at 6-month follow-up.

Plaquelike myofibroblastic tumor is an unusual pediatric dermal tumor that was first described by Clarke et al¹ in 2007. Clinical manifestation of PLMT on the right abdomen was unique in our patient, as the lesions typically present as indurated plaques on the lower back, but the central ulceration in our case resembled a report by Marqueling et al.² Ulceration and induration of PLMT developing at 8 months of age can suggest an aggressive disease course corresponding with deep infiltration and is seen mostly in children.

The histopathologic features of PLMT include an acanthotic epidermis and follicular induction, which also are characteristic of dermatofibroma (DF). The proliferation of spindle cells extended deep into the fat with foci of erythrocyte extravasation and microvesiculation of the stroma similar to nodular fasciitis and proliferative fasciitis. The presentation of infiltrating and expanding fibrous septae and trapping of individual adipocytes in a honeycomb pattern is similar to dermatofibrosarcoma protuberans (DFSP). Most cases of PLMT are positive for SMA. Factor XIIIa typically is variably positive, and in one report, 31% (4/13) of cases showed positive staining for calponin.³ Rapid growth, ulceration, and recurrence emphasize that PLMT can be locally aggressive, similar to DFSP.⁴

The main differential diagnoses include DF and its variants, dermatomyofibroma, DFSP, and proliferative fasciitis.^3,5 In the cases mentioned above, microscopic features were similar with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles through the entire reticular dermis, and the overlying epidermis was acanthotic.

Dermatofibroma commonly manifests in adults as a minor nodular lesion (commonly <1 cm), and usually is located on the legs. It has several clinical and histologic variants, including multiple clustered DF (MCDF)—a rare condition that has been reported in children and young adults and generally appears in the first and second decades of life. Of the reported cases of MCDF, immunohistochemical staining for SMA was performed in 8 cases. All these cases showed negative or minimal staining.^3-5 Smooth muscle actin staining in DFs is negative, or weak and patchy, unlike in PLMT where it is diffuse, uniform, and strong.

Dermatofibrosarcoma protuberans typically occurs in young adults and manifests as dermal and subcutaneous nodular/multinodular or plaquelike masses, with rare congenital cases. Immunohistochemical staining for CD34, which typically is firmly and diffusely positive, is the most reliable marker of DFSP.⁶ Factor XIIIA in DFSP typically is negative for focal staining, mainly at periphery or in scattered dendritic cells. The prognosis of DFSP generally is excellent, with local recurrences in up to 30% of cases and extremely low metastatic potential (essentially only in cases with fibrosarcomatous transformation).⁶ Dermatomyofibroma is another rare benign dermal myofibroblastic tumor that typically manifests with indurated hyperpigmented or erythematous plaques or nodules on the shoulders and torso.⁶ This condition occurs mainly in adolescents and young adults, unlike PLMT. The most striking features of dermatomyofibroma are the horizontal orientation of the spindle cell nuclei and the pattern of the proliferation concerning the adnexal structures, especially hair follicles. The hair follicles have a normal appearance, and the proliferation extends up to each follicle, then continues to the other side without any displacement of the follicle. Tumor cells are variably positive for SMA in dermatomyofibromas and are negative for muscle-specific actin, desmin, S100, CD34, and Factor XIIIA.⁶

Immunohistochemistry can be very useful in differentiating PLMT from other conditions. Neoplastic cells stain positively for CD34 but not for Factor XIIIa and SMA in cases of DFSP. Dermatofibroma and its variants always present with collagen trapping at the periphery of the lesions and may demonstrate foamy macrophages, hemosiderin, or plasma cells FXIIIA(+), CD34(-), and variable SMA reactivity. This positivity usually is less prominent in DF than in PLMT. Neoplastic cells in dermatomyofibroma often stain positive for calponin, but only focally for SMA. The clinical features of dermatomyofibroma include early onset, large size, multiple nodules, and plaquelike morphology. Moulonguet et al⁴ hypothesized that, although MCDF and PLMT appear to show some distinctive clinical and histologic features, they also show similarities that could suggest they form part of the myofibroblastic spectrum. Furthermore, Moradi et al⁷ also considered them as part of the same disease spectrum because of their overlapping clinical, histologic, and immunohistochemical features.

The microscopic features in our case are notable, as the lesion demonstrated overlying acanthosis and follicular induction, resembling DF. The stroma contained microvesicular changes and erythrocyte extravasation, characteristic of nodular or proliferative fasciitis. Additionally, densely packed spindle cells infiltrated deep into the subcutaneous adipose tissue, similar to DFSP.^2,3 Our findings expand on the reported histopathologic spectrum of this tumor to date.

THE DIAGNOSIS: Plaquelike Myofibroblastic Tumor

An incisional biopsy of the plaque demonstrated a hypercellular proliferation of bland spindle cells in the dermis that infiltrated the subcutis. The overlying epidermis was mildly acanthotic with both ulceration and follicular induction. There was trapping of individual adipocytes in a honeycomb pattern with foci of erythrocyte extravasation, microvesiculation, and widened fibrous septa (Figure 1). Immunohistochemistry was positive for vimentin, actin, and smooth muscle actin (SMA)(Figure 2A). Variable positivity for Factor XIIIa antibodies was noted. CD68 staining was focal positive, suggesting fibrohistiocytic lineage. Expression of CD31, CD34, S100, and anaplastic lymphoma kinase was negative, and Ki-67 was present in less than 10% of cells (Figure 2B).

We reviewed the case in conjunction with a soft-tissue pathologist (Y.L.), and based on the clinical and immunophenotypic features, a diagnosis of plaquelike myofibroblastic tumor (PLMT) was made. The patient’s parents refused further treatment, and there was no sign of disease progression at 6-month follow-up.

Plaquelike myofibroblastic tumor is an unusual pediatric dermal tumor that was first described by Clarke et al¹ in 2007. Clinical manifestation of PLMT on the right abdomen was unique in our patient, as the lesions typically present as indurated plaques on the lower back, but the central ulceration in our case resembled a report by Marqueling et al.² Ulceration and induration of PLMT developing at 8 months of age can suggest an aggressive disease course corresponding with deep infiltration and is seen mostly in children.

The histopathologic features of PLMT include an acanthotic epidermis and follicular induction, which also are characteristic of dermatofibroma (DF). The proliferation of spindle cells extended deep into the fat with foci of erythrocyte extravasation and microvesiculation of the stroma similar to nodular fasciitis and proliferative fasciitis. The presentation of infiltrating and expanding fibrous septae and trapping of individual adipocytes in a honeycomb pattern is similar to dermatofibrosarcoma protuberans (DFSP). Most cases of PLMT are positive for SMA. Factor XIIIa typically is variably positive, and in one report, 31% (4/13) of cases showed positive staining for calponin.³ Rapid growth, ulceration, and recurrence emphasize that PLMT can be locally aggressive, similar to DFSP.⁴

The main differential diagnoses include DF and its variants, dermatomyofibroma, DFSP, and proliferative fasciitis.^3,5 In the cases mentioned above, microscopic features were similar with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles through the entire reticular dermis, and the overlying epidermis was acanthotic.

Dermatofibroma commonly manifests in adults as a minor nodular lesion (commonly <1 cm), and usually is located on the legs. It has several clinical and histologic variants, including multiple clustered DF (MCDF)—a rare condition that has been reported in children and young adults and generally appears in the first and second decades of life. Of the reported cases of MCDF, immunohistochemical staining for SMA was performed in 8 cases. All these cases showed negative or minimal staining.^3-5 Smooth muscle actin staining in DFs is negative, or weak and patchy, unlike in PLMT where it is diffuse, uniform, and strong.

Dermatofibrosarcoma protuberans typically occurs in young adults and manifests as dermal and subcutaneous nodular/multinodular or plaquelike masses, with rare congenital cases. Immunohistochemical staining for CD34, which typically is firmly and diffusely positive, is the most reliable marker of DFSP.⁶ Factor XIIIA in DFSP typically is negative for focal staining, mainly at periphery or in scattered dendritic cells. The prognosis of DFSP generally is excellent, with local recurrences in up to 30% of cases and extremely low metastatic potential (essentially only in cases with fibrosarcomatous transformation).⁶ Dermatomyofibroma is another rare benign dermal myofibroblastic tumor that typically manifests with indurated hyperpigmented or erythematous plaques or nodules on the shoulders and torso.⁶ This condition occurs mainly in adolescents and young adults, unlike PLMT. The most striking features of dermatomyofibroma are the horizontal orientation of the spindle cell nuclei and the pattern of the proliferation concerning the adnexal structures, especially hair follicles. The hair follicles have a normal appearance, and the proliferation extends up to each follicle, then continues to the other side without any displacement of the follicle. Tumor cells are variably positive for SMA in dermatomyofibromas and are negative for muscle-specific actin, desmin, S100, CD34, and Factor XIIIA.⁶

Immunohistochemistry can be very useful in differentiating PLMT from other conditions. Neoplastic cells stain positively for CD34 but not for Factor XIIIa and SMA in cases of DFSP. Dermatofibroma and its variants always present with collagen trapping at the periphery of the lesions and may demonstrate foamy macrophages, hemosiderin, or plasma cells FXIIIA(+), CD34(-), and variable SMA reactivity. This positivity usually is less prominent in DF than in PLMT. Neoplastic cells in dermatomyofibroma often stain positive for calponin, but only focally for SMA. The clinical features of dermatomyofibroma include early onset, large size, multiple nodules, and plaquelike morphology. Moulonguet et al⁴ hypothesized that, although MCDF and PLMT appear to show some distinctive clinical and histologic features, they also show similarities that could suggest they form part of the myofibroblastic spectrum. Furthermore, Moradi et al⁷ also considered them as part of the same disease spectrum because of their overlapping clinical, histologic, and immunohistochemical features.

The microscopic features in our case are notable, as the lesion demonstrated overlying acanthosis and follicular induction, resembling DF. The stroma contained microvesicular changes and erythrocyte extravasation, characteristic of nodular or proliferative fasciitis. Additionally, densely packed spindle cells infiltrated deep into the subcutaneous adipose tissue, similar to DFSP.^2,3 Our findings expand on the reported histopathologic spectrum of this tumor to date.

The yellow fly (Diachlorus ferrugatus) is a flying biting insect belonging to the order Diptera, family Tabanidae, which also includes deer flies (genus Chrysops) and horse flies (genus Tabanus).¹ They are different from stinging insects of the order Hymenoptera (bees, wasps, yellow jackets, and hornets). As the name suggests, the yellow fly has a distinct yellow appearance, and adult yellow flies have a body length of approximately 1 cm.^1,2 Distinguishing features of the yellow fly include prominently dark forelegs (the remaining legs are yellow), dark purple to black eyes with 2 fluorescent green lines, and a yellow abdomen with black hairs along the lateral regions and a broad central yellow stripe.^1-3 Their wings have longitudinal black veins with clear spaces in between and a conspicuous brown patch at the apex (Figure 1A). In comparison, horse flies are darker and larger (Figure 1B), and deer flies are similar in shape but have stripes on the abdomen and thorax and mottled wings with dark patches near the apex (Figure 1C).¹

The Tabanidae family comprises 4455 species belonging to 137 genera and is notorious for bites that result in localized pain, swelling, itching, and discomfort.⁴ While some Tabanidae species are mechanical or biologic vectors of pathogens (eg, Loa loa, equine infectious anemia virus, Trypanosoma species, cattle and sheep anthrax and tularemia), yellow flies do not appear to play a considerable role in disease transmission.^4,5 Nonetheless, their bites can cause discomfort and create a nuisance for individuals residing within their distribution areas as well as for agricultural livestock, contributing to lower weight gain and milk production.¹

Yellow flies are a commonly occurring species in the southeastern United States; their distribution spans several states, including New Jersey, Florida, and Texas.^1,2 In Florida, specifically, yellow flies exhibit a seasonal pattern, with peak activity typically occurring from April through June.^6-9 Activity levels are heightened around sunset as well as sunrise.^1,9 Tabanids can be found in forests, parks, and gardens—particularly those that contain waterways such as freshwater lakes and streams—and typically stay near shaded woodlands that are prone to flooding.⁹

Tabanids go through the life cycle stages of egg, larva, pupa, and adult; the life cycle typically spans 1 year, with the adults living 30 to 60 days.¹ Mating occurs soon after adults emerge from the pupal case in the soil.^1,10 Females then are attracted to large dark moving objects and will feed on blood to develop eggs.^2,10 Only female members of the Tabanidae family have modifications of the mouth parts that allow wounding of the skin (Figure 2). Their bites introduce saliva to the skin containing anticoagulants and other likely allergens. The tongue is used to lap between 20 to 600 microliters of blood.¹¹ Males feed primarily on pollen and nectar.¹⁰ Most tabanid bites result in transient wheal-and-flare reactions, but some can result in more severe allergic reactions such as in our reported case.¹⁰ Rarely, anaphylactic reactions have been documented.^10,12

Case Report

A 48-year-old man presented with swelling of the left hand following a yellow fly bite to the wrist 30 minutes prior while he worked outside at a ranch in central Florida (Figure 3). The patient was afebrile and reported no respiratory or gastrointestinal symptoms. The left hand and forearm were warm to the touch and appeared red and edematous (Figure 4). He was not tachycardic and did not appear to be in any distress. The patient reported that he had worked on the ranch for several years, and during that time had noted he was developing worsening localized reactions to yellow fly bites. He had visually identified the offending insect prior to the current presentation and had trapped some flies in previous incidents. Recently he had experienced rapid swelling at the bite sites but had never experienced respiratory difficulties or signs of systemic allergic reactions. He previously had used topical steroids when bites resulted in mild wheal-and-flare reactions, but he reported that these were no longer effective.

Management of the current bite reaction included oral prednisone tapered over 1 week from 40 mg to 10 mg daily as well as oral cetirizine 10 mg daily. Although bacterial cellulitis was considered in the differential diagnosis, no oral antibiotics were prescribed given the patient’s history of similar clinical presentations following yellow fly bites. His symptoms resolved within a few hours of his dose of prednisone. Incidentally, our patient has been able to control the progression of subsequent hypersensitivity reactions to yellow fly bites with a single 20-mg dose of prednisone administered at the onset of the bite.

Comment

In general, blood-feeding (hematophagous) insects rarely cause anaphylaxis and are more likely to cause cutaneous hypersensitivity reactions, possibly due to the small amount of antigen injected from a bite.^13,14 The immediate wheal-and-flare reaction is an IgE-mediated type 1 immune reaction compared to a less common type 4 T-cell mediated delayed hypersensitivity reaction.^14,15 There are many protein allergens in the saliva of biting insects that are not well characterized. Relevant allergens include a 69 kDa salivary gland protein as well as a Tab y 1 (anticoagulant), Tab y 2 (hyaluronidase), and Tab y 5 (antigen 5–related venom protein).^11,15-17 Some of these proteins have structural homology between insects of different orders and can cause cross-reactivity in patients who also are allergic to Hymenoptera stings (wasp-horsefly syndrome).^12,16

Our patient’s cutaneous reaction was localized and clinically manifested with rapidly progressive erythema and edema at the bite location. He did not exhibit signs of a systemic reaction such as angioedema, respiratory or gastrointestinal symptoms, tachycardia, or hypotension. Management of affected patients depends on the extent of the reaction and may include oral or parenteral antihistamines as well as oral steroids for more severe edema.¹¹ Anaphylactic reactions generally respond to subcutaneous epinephrine.¹⁵ It would be prudent for patients with a relevant anaphylactic history to carry an autoinjectable epinephrine pen in case of difficulty breathing or general malaise following a bite. Besides avoidance of insect bites, personal protection methods include wearing long-sleeved shirts and pants and using insect repellents containing diethyl toluamide (DEET), citronella, or geraniol.¹

At present, diagnosis of cutaneous reactions to yellow fly bites is best made based on the patient’s personal history.¹⁴ If the offending fly is trapped, it can be identified. As most patients cannot differentiate between insects, it may be helpful for dermatologists to know that a small amount of blood at the bite site is suggestive of a fly bite rather than a sting from a member of the order Hymenoptera. Currently, there are no consistently useful extracts for intradermal skin testing.¹¹ Although there are several commercially available serum-specific IgE tests for suspected horse fly reactions, their usefulness is doubtful without further information on sensitivity and specificity as well as the allergen utilized.^11,18,19 The use of allergen immunotherapy to induce hyposensitization in patients who experience cutaneous reactions is not standardized and poses some risks including severe allergic reactions requiring facilities for resuscitation, variability of response patterns, and supporting evidence is weak.¹¹

Final Thoughts

Cutaneous reactions to yellow fly bites rarely are described in the dermatology literature. The salivary proteins implicated in inducing an allergic response and cross-reactivity of D ferrugatus with other biting and stinging insects as well as the natural course of immune reactions over time need to be further characterized.

The yellow fly (Diachlorus ferrugatus) is a flying biting insect belonging to the order Diptera, family Tabanidae, which also includes deer flies (genus Chrysops) and horse flies (genus Tabanus).¹ They are different from stinging insects of the order Hymenoptera (bees, wasps, yellow jackets, and hornets). As the name suggests, the yellow fly has a distinct yellow appearance, and adult yellow flies have a body length of approximately 1 cm.^1,2 Distinguishing features of the yellow fly include prominently dark forelegs (the remaining legs are yellow), dark purple to black eyes with 2 fluorescent green lines, and a yellow abdomen with black hairs along the lateral regions and a broad central yellow stripe.^1-3 Their wings have longitudinal black veins with clear spaces in between and a conspicuous brown patch at the apex (Figure 1A). In comparison, horse flies are darker and larger (Figure 1B), and deer flies are similar in shape but have stripes on the abdomen and thorax and mottled wings with dark patches near the apex (Figure 1C).¹

The Tabanidae family comprises 4455 species belonging to 137 genera and is notorious for bites that result in localized pain, swelling, itching, and discomfort.⁴ While some Tabanidae species are mechanical or biologic vectors of pathogens (eg, Loa loa, equine infectious anemia virus, Trypanosoma species, cattle and sheep anthrax and tularemia), yellow flies do not appear to play a considerable role in disease transmission.^4,5 Nonetheless, their bites can cause discomfort and create a nuisance for individuals residing within their distribution areas as well as for agricultural livestock, contributing to lower weight gain and milk production.¹

Yellow flies are a commonly occurring species in the southeastern United States; their distribution spans several states, including New Jersey, Florida, and Texas.^1,2 In Florida, specifically, yellow flies exhibit a seasonal pattern, with peak activity typically occurring from April through June.^6-9 Activity levels are heightened around sunset as well as sunrise.^1,9 Tabanids can be found in forests, parks, and gardens—particularly those that contain waterways such as freshwater lakes and streams—and typically stay near shaded woodlands that are prone to flooding.⁹

Tabanids go through the life cycle stages of egg, larva, pupa, and adult; the life cycle typically spans 1 year, with the adults living 30 to 60 days.¹ Mating occurs soon after adults emerge from the pupal case in the soil.^1,10 Females then are attracted to large dark moving objects and will feed on blood to develop eggs.^2,10 Only female members of the Tabanidae family have modifications of the mouth parts that allow wounding of the skin (Figure 2). Their bites introduce saliva to the skin containing anticoagulants and other likely allergens. The tongue is used to lap between 20 to 600 microliters of blood.¹¹ Males feed primarily on pollen and nectar.¹⁰ Most tabanid bites result in transient wheal-and-flare reactions, but some can result in more severe allergic reactions such as in our reported case.¹⁰ Rarely, anaphylactic reactions have been documented.^10,12

Case Report

A 48-year-old man presented with swelling of the left hand following a yellow fly bite to the wrist 30 minutes prior while he worked outside at a ranch in central Florida (Figure 3). The patient was afebrile and reported no respiratory or gastrointestinal symptoms. The left hand and forearm were warm to the touch and appeared red and edematous (Figure 4). He was not tachycardic and did not appear to be in any distress. The patient reported that he had worked on the ranch for several years, and during that time had noted he was developing worsening localized reactions to yellow fly bites. He had visually identified the offending insect prior to the current presentation and had trapped some flies in previous incidents. Recently he had experienced rapid swelling at the bite sites but had never experienced respiratory difficulties or signs of systemic allergic reactions. He previously had used topical steroids when bites resulted in mild wheal-and-flare reactions, but he reported that these were no longer effective.

Management of the current bite reaction included oral prednisone tapered over 1 week from 40 mg to 10 mg daily as well as oral cetirizine 10 mg daily. Although bacterial cellulitis was considered in the differential diagnosis, no oral antibiotics were prescribed given the patient’s history of similar clinical presentations following yellow fly bites. His symptoms resolved within a few hours of his dose of prednisone. Incidentally, our patient has been able to control the progression of subsequent hypersensitivity reactions to yellow fly bites with a single 20-mg dose of prednisone administered at the onset of the bite.

Comment

In general, blood-feeding (hematophagous) insects rarely cause anaphylaxis and are more likely to cause cutaneous hypersensitivity reactions, possibly due to the small amount of antigen injected from a bite.^13,14 The immediate wheal-and-flare reaction is an IgE-mediated type 1 immune reaction compared to a less common type 4 T-cell mediated delayed hypersensitivity reaction.^14,15 There are many protein allergens in the saliva of biting insects that are not well characterized. Relevant allergens include a 69 kDa salivary gland protein as well as a Tab y 1 (anticoagulant), Tab y 2 (hyaluronidase), and Tab y 5 (antigen 5–related venom protein).^11,15-17 Some of these proteins have structural homology between insects of different orders and can cause cross-reactivity in patients who also are allergic to Hymenoptera stings (wasp-horsefly syndrome).^12,16

Our patient’s cutaneous reaction was localized and clinically manifested with rapidly progressive erythema and edema at the bite location. He did not exhibit signs of a systemic reaction such as angioedema, respiratory or gastrointestinal symptoms, tachycardia, or hypotension. Management of affected patients depends on the extent of the reaction and may include oral or parenteral antihistamines as well as oral steroids for more severe edema.¹¹ Anaphylactic reactions generally respond to subcutaneous epinephrine.¹⁵ It would be prudent for patients with a relevant anaphylactic history to carry an autoinjectable epinephrine pen in case of difficulty breathing or general malaise following a bite. Besides avoidance of insect bites, personal protection methods include wearing long-sleeved shirts and pants and using insect repellents containing diethyl toluamide (DEET), citronella, or geraniol.¹

At present, diagnosis of cutaneous reactions to yellow fly bites is best made based on the patient’s personal history.¹⁴ If the offending fly is trapped, it can be identified. As most patients cannot differentiate between insects, it may be helpful for dermatologists to know that a small amount of blood at the bite site is suggestive of a fly bite rather than a sting from a member of the order Hymenoptera. Currently, there are no consistently useful extracts for intradermal skin testing.¹¹ Although there are several commercially available serum-specific IgE tests for suspected horse fly reactions, their usefulness is doubtful without further information on sensitivity and specificity as well as the allergen utilized.^11,18,19 The use of allergen immunotherapy to induce hyposensitization in patients who experience cutaneous reactions is not standardized and poses some risks including severe allergic reactions requiring facilities for resuscitation, variability of response patterns, and supporting evidence is weak.¹¹

Final Thoughts

Cutaneous reactions to yellow fly bites rarely are described in the dermatology literature. The salivary proteins implicated in inducing an allergic response and cross-reactivity of D ferrugatus with other biting and stinging insects as well as the natural course of immune reactions over time need to be further characterized.

The yellow fly (Diachlorus ferrugatus) is a flying biting insect belonging to the order Diptera, family Tabanidae, which also includes deer flies (genus Chrysops) and horse flies (genus Tabanus).¹ They are different from stinging insects of the order Hymenoptera (bees, wasps, yellow jackets, and hornets). As the name suggests, the yellow fly has a distinct yellow appearance, and adult yellow flies have a body length of approximately 1 cm.^1,2 Distinguishing features of the yellow fly include prominently dark forelegs (the remaining legs are yellow), dark purple to black eyes with 2 fluorescent green lines, and a yellow abdomen with black hairs along the lateral regions and a broad central yellow stripe.^1-3 Their wings have longitudinal black veins with clear spaces in between and a conspicuous brown patch at the apex (Figure 1A). In comparison, horse flies are darker and larger (Figure 1B), and deer flies are similar in shape but have stripes on the abdomen and thorax and mottled wings with dark patches near the apex (Figure 1C).¹

The Tabanidae family comprises 4455 species belonging to 137 genera and is notorious for bites that result in localized pain, swelling, itching, and discomfort.⁴ While some Tabanidae species are mechanical or biologic vectors of pathogens (eg, Loa loa, equine infectious anemia virus, Trypanosoma species, cattle and sheep anthrax and tularemia), yellow flies do not appear to play a considerable role in disease transmission.^4,5 Nonetheless, their bites can cause discomfort and create a nuisance for individuals residing within their distribution areas as well as for agricultural livestock, contributing to lower weight gain and milk production.¹

Yellow flies are a commonly occurring species in the southeastern United States; their distribution spans several states, including New Jersey, Florida, and Texas.^1,2 In Florida, specifically, yellow flies exhibit a seasonal pattern, with peak activity typically occurring from April through June.^6-9 Activity levels are heightened around sunset as well as sunrise.^1,9 Tabanids can be found in forests, parks, and gardens—particularly those that contain waterways such as freshwater lakes and streams—and typically stay near shaded woodlands that are prone to flooding.⁹

Tabanids go through the life cycle stages of egg, larva, pupa, and adult; the life cycle typically spans 1 year, with the adults living 30 to 60 days.¹ Mating occurs soon after adults emerge from the pupal case in the soil.^1,10 Females then are attracted to large dark moving objects and will feed on blood to develop eggs.^2,10 Only female members of the Tabanidae family have modifications of the mouth parts that allow wounding of the skin (Figure 2). Their bites introduce saliva to the skin containing anticoagulants and other likely allergens. The tongue is used to lap between 20 to 600 microliters of blood.¹¹ Males feed primarily on pollen and nectar.¹⁰ Most tabanid bites result in transient wheal-and-flare reactions, but some can result in more severe allergic reactions such as in our reported case.¹⁰ Rarely, anaphylactic reactions have been documented.^10,12

Case Report

A 48-year-old man presented with swelling of the left hand following a yellow fly bite to the wrist 30 minutes prior while he worked outside at a ranch in central Florida (Figure 3). The patient was afebrile and reported no respiratory or gastrointestinal symptoms. The left hand and forearm were warm to the touch and appeared red and edematous (Figure 4). He was not tachycardic and did not appear to be in any distress. The patient reported that he had worked on the ranch for several years, and during that time had noted he was developing worsening localized reactions to yellow fly bites. He had visually identified the offending insect prior to the current presentation and had trapped some flies in previous incidents. Recently he had experienced rapid swelling at the bite sites but had never experienced respiratory difficulties or signs of systemic allergic reactions. He previously had used topical steroids when bites resulted in mild wheal-and-flare reactions, but he reported that these were no longer effective.

Management of the current bite reaction included oral prednisone tapered over 1 week from 40 mg to 10 mg daily as well as oral cetirizine 10 mg daily. Although bacterial cellulitis was considered in the differential diagnosis, no oral antibiotics were prescribed given the patient’s history of similar clinical presentations following yellow fly bites. His symptoms resolved within a few hours of his dose of prednisone. Incidentally, our patient has been able to control the progression of subsequent hypersensitivity reactions to yellow fly bites with a single 20-mg dose of prednisone administered at the onset of the bite.

Comment

In general, blood-feeding (hematophagous) insects rarely cause anaphylaxis and are more likely to cause cutaneous hypersensitivity reactions, possibly due to the small amount of antigen injected from a bite.^13,14 The immediate wheal-and-flare reaction is an IgE-mediated type 1 immune reaction compared to a less common type 4 T-cell mediated delayed hypersensitivity reaction.^14,15 There are many protein allergens in the saliva of biting insects that are not well characterized. Relevant allergens include a 69 kDa salivary gland protein as well as a Tab y 1 (anticoagulant), Tab y 2 (hyaluronidase), and Tab y 5 (antigen 5–related venom protein).^11,15-17 Some of these proteins have structural homology between insects of different orders and can cause cross-reactivity in patients who also are allergic to Hymenoptera stings (wasp-horsefly syndrome).^12,16

Our patient’s cutaneous reaction was localized and clinically manifested with rapidly progressive erythema and edema at the bite location. He did not exhibit signs of a systemic reaction such as angioedema, respiratory or gastrointestinal symptoms, tachycardia, or hypotension. Management of affected patients depends on the extent of the reaction and may include oral or parenteral antihistamines as well as oral steroids for more severe edema.¹¹ Anaphylactic reactions generally respond to subcutaneous epinephrine.¹⁵ It would be prudent for patients with a relevant anaphylactic history to carry an autoinjectable epinephrine pen in case of difficulty breathing or general malaise following a bite. Besides avoidance of insect bites, personal protection methods include wearing long-sleeved shirts and pants and using insect repellents containing diethyl toluamide (DEET), citronella, or geraniol.¹

At present, diagnosis of cutaneous reactions to yellow fly bites is best made based on the patient’s personal history.¹⁴ If the offending fly is trapped, it can be identified. As most patients cannot differentiate between insects, it may be helpful for dermatologists to know that a small amount of blood at the bite site is suggestive of a fly bite rather than a sting from a member of the order Hymenoptera. Currently, there are no consistently useful extracts for intradermal skin testing.¹¹ Although there are several commercially available serum-specific IgE tests for suspected horse fly reactions, their usefulness is doubtful without further information on sensitivity and specificity as well as the allergen utilized.^11,18,19 The use of allergen immunotherapy to induce hyposensitization in patients who experience cutaneous reactions is not standardized and poses some risks including severe allergic reactions requiring facilities for resuscitation, variability of response patterns, and supporting evidence is weak.¹¹

Final Thoughts

Cutaneous reactions to yellow fly bites rarely are described in the dermatology literature. The salivary proteins implicated in inducing an allergic response and cross-reactivity of D ferrugatus with other biting and stinging insects as well as the natural course of immune reactions over time need to be further characterized.

While patch testing is the gold standard to diagnose type IV cutaneous hypersensitivity reactions, interpreting results can feel like trying to decipher a secret code, leaving patients feeling disempowered in avoiding their triggers. To truly manage allergic contact dermatitis (ACD), patients need comprehensive education on which allergens to avoid and ways to spot potential sources of exposure, including counseling, written guidelines, and lists of product alternatives.¹ Patients who can recall and avoid their triggers experience greater improvement in clinical and quality-of-life scores.² However, several studies have demonstrated that patients have difficulty recalling their allergens, even with longitudinal reminders.^2-5 Quality-of-life and clinical outcomes also are not necessarily improved by successful allergen recall alone, as patients have reported limited success in actually avoiding allergens, highlighting the complexity of navigating exposures in daily life.^2,6 To address these challenges, we examine common pitfalls patients encounter when avoiding allergens, highlight the benefits of utilizing safe lists and databases for allergen management, and introduce the updated Contact Allergen Management Program (CAMP) 2.0 as an optimal tool for long-term management of ACD.

Allergen Avoidance Pitfalls

Simply reading ingredient labels to avoid allergens is only marginally effective, as patients need to identify and interpret multiple chemical names as well as cross-reactors and related compounds to achieve success. Some allergens, such as fragrances or manufacturing impurities, are not explicitly identified on product labels. Even patients who can practice diligent label reading may struggle to find information on household or occupational products when full ingredient disclosure is not required.

Many of the allergens included in the American Contact Dermatitis Society (ACDS) Core 90 Series have alternative chemical aliases, and many have related compounds.⁶ For example, individuals with contact allergy to formaldehyde or a formaldehyde releaser usually need to avoid multiple other formaldehyde-releasing chemicals. Patients who test positive to amidoamine or dimethylaminopropylamine also must avoid the surfactant cocamidopropyl betaine—not because it is a cross-reactor, but because it is an impurity in the synthetic pathway.

Fragrance is one of the most common causes of ACD but can be challenging to avoid. Patients with allergies to fragrance or specific compounds (eg, limonene, linalool hydroperoxides) need to be savvy enough to navigate a broad spectrum of synthetic and botanical fragrance additives. Avoiding products that contain “fragrance” or “parfum” is simple enough, but patients also may need to recognize more than 3000 chemical names to identify individual fragrance ingredients that may be listed separately.⁷ Further, some fragrances are added for alternative purposes—preservative, medicinal, or emulsification—in which case products may deceptively tout themselves as being “fragrance free” yet still contain a fragrance allergen. This is made even more complex considering additional additives that commonly may cross-react with individual fragrance compounds; balsam of Peru, for example, is a botanical amalgam containing more than 250 compounds, including several fragrance components, making it an excellent indicator of fragrance allergy.⁸ While balsam of Peru and its fragrance constituents will almost never be listed on a product label, it cross-reacts with several benzyl derivatives commonly used in cosmetic formulations, such as benzyl alcohol, benzyl acetate, benzoic acid, benzyl benzoate, and benzyl cinnamate.^9,10

Given that ACD is a common reason for patients to seek dermatologic care, it is crucial for clinicians to equip themselves with effective strategies to support patients after patch testing.¹¹ This includes efficient translation of patch test results into practical advice while avoiding the oversimplified suggestion to read product labels; however, education alone cannot address the complexities of managing ACD, which is where contact allergen databases come into play.

An Essential Tool: Patient Allergen Databases and Safe Lists

Contact allergen databases are like a trusty sidekick for patients and clinicians, providing easily accessible information and tools to support allergen avoidance and improve ACD outcomes. While there are several existing resources, the ACDS launched its CAMP database in 2011 for ACDS members and their patients.¹² The CAMP allows clinicians to easily generate personalized safe lists for household, medicament, and personal care products, facilitating seamless patient access both online and via a mobile application. The database also includes allergen-specific handouts to guide patient education.¹³ A key highlight of the CAMP is automated management of cross-reactors, which allows patients to choose products without having to memorize complex cross-reactor algorithms and helps avoid overly restrictive safe lists (Table).^12-15

Other databases and online resources provide similar features, such as resources for patient education or finding safe products. The 2018 Alternatives for Allergens report is a vital adjunctive resource for guiding patients to suitable allergen-free products not included in commonly accessible product databases such as occupational materials, medical adhesives, shoes, or textiles.¹⁶

Introduction of CAMP 2.0

The latest version, CAMP 2.0, was launched in late 2024. The fully revamped database has a catalog of more than 100,000 products and comes packed with features that address many of the limitations found in the original CAMP. How does CAMP 2.0 work? The clinician inputs the patient’s allergens and makes choices about cross-reactor groups, and CAMP 2.0 outputs a list of allergen-free products that the patient can use when shopping for personal care products and the clinician can use for prescribing medicaments. The new user experience is intended to be more informative and engaging for all parties.

The CAMP 2.0 interface offers frequent product updates and streamlined database navigation, including enhanced search functions, barcode scanning, and a new mobile application for Apple and Android users. The mobile application also allows patients to track their symptoms and quality of life over time. With this additional functionality, there also is an extensive section for frequently asked questions and tutorials to help patients understand and utilize these features effectively.

Patients no longer have to wonder if a product that is not listed on their safe list is actually unsafe or just missing from the database. Several new features, including color-coded ingredient lists and organization of search codes into “safe” and “unsafe” product lists (Figure 1), help increase product transparency. These features can facilitate patient recognition of allergen names and cross-reactors in selected products. Future updates will include product purchasing through the mobile application and more educational handouts, including Spanish translations and dietary guidelines for systemic contact dermatitis.

Patient Experience—Once patients complete patch testing with an ACDS member, they can access the CAMP 2.0 database for free via web-based or a mobile application. After setting up an account, patients gain immediate access to their allergen information, product database, and educational resources about ACD and CAMP 2.0. Patients can search for specific products using text or barcode scanning or browse through categorized lists of medical, household, and personal care items. Each product page contains the product name and brand along with a color-coded ingredient list to help patients identify safe and unsafe ingredients at a glance (Figure 1). Products not currently included in the database can be requested using the “Add Product” feature. Additional patient engagement features include options to mark favorite products, write reviews, and track quality of life over time.

Physician Experience—The updated version includes several tutorials and frequently asked questions on how to improve ACD management and make the most of the new CAMP 2.0 tools and features. Generating patient allergen codes has been streamlined with an “Allergen Search” feature, allowing providers to quickly search and add or remove allergens to patients’ safe lists. Cross-reactor groups may be selectively added or removed for greater transparency and specificity in creating a patient safe list (Figure 2). Allergen codes now can be edited over time and are available for patient use via alphanumeric text or QR code format, which easily can be printed on a handout with instructions to help patients get acquainted with the system. For patient counseling, updated education handouts are available in the patient’s app and may be printed to provide supportive written educational material.

Approach to Long-Term Follow-up

When it comes to getting the most from patch testing, ongoing allergen avoidance is crucial. Patients may not see improvement unless they understand what ACD is and what needs to be done to improve it as well as become familiar with the names and common sources of their triggers.¹⁷ Clinicians can use CAMP 2.0 to facilitate patient improvement after patch testing, focusing on 3 key areas: continued patient education, patients’ ongoing progress in avoiding allergens, and monitored clinical improvement.

A solid understanding of ACD, such as its delayed (ie, 24-72 hours) onset after exposure, the need for allergen avoidance for at least 4 to 6 weeks before seeing improvement, and correlation of identified allergens with daily exposures, plays a major role in patient success. The CAMP 2.0 patch testing basics section is an excellent resource for patient-friendly explanations on patch testing and ACD. This resource, as well as allergen education handouts, may be reviewed at follow-up visits to continue to solidify patient learning.

Patients often have questions about allergen avoidance, such as occupational exposures, the suitability of specific products, or specific allergen names. These discussions are helpful for gauging how well patients are equipped to avoid their triggers as well as any hurdles they may be facing. If a patient still is experiencing flares after 6 to 8 weeks of safe-list adherence, it is important to take a thorough history of product use, daily exposures, and the patterns of distribution on the skin. Possible allergen exposures via topical medications also should be considered.^18,19 Cross-checking products with a patient’s CAMP 2.0 safe list and correlating exposures with the continued ACD distribution are effective strategies to troubleshoot for unknown exposures to allergens.

Final Thoughts

Helping patients avoid allergens is essential to long-term management of ACD. The CAMP 2.0 safe list is an essential tool and a comprehensive reference for both patients and clinicians. With CAMP 2.0, allergen avoidance has never been more interactive or accessible.

While patch testing is the gold standard to diagnose type IV cutaneous hypersensitivity reactions, interpreting results can feel like trying to decipher a secret code, leaving patients feeling disempowered in avoiding their triggers. To truly manage allergic contact dermatitis (ACD), patients need comprehensive education on which allergens to avoid and ways to spot potential sources of exposure, including counseling, written guidelines, and lists of product alternatives.¹ Patients who can recall and avoid their triggers experience greater improvement in clinical and quality-of-life scores.² However, several studies have demonstrated that patients have difficulty recalling their allergens, even with longitudinal reminders.^2-5 Quality-of-life and clinical outcomes also are not necessarily improved by successful allergen recall alone, as patients have reported limited success in actually avoiding allergens, highlighting the complexity of navigating exposures in daily life.^2,6 To address these challenges, we examine common pitfalls patients encounter when avoiding allergens, highlight the benefits of utilizing safe lists and databases for allergen management, and introduce the updated Contact Allergen Management Program (CAMP) 2.0 as an optimal tool for long-term management of ACD.

Allergen Avoidance Pitfalls

Simply reading ingredient labels to avoid allergens is only marginally effective, as patients need to identify and interpret multiple chemical names as well as cross-reactors and related compounds to achieve success. Some allergens, such as fragrances or manufacturing impurities, are not explicitly identified on product labels. Even patients who can practice diligent label reading may struggle to find information on household or occupational products when full ingredient disclosure is not required.

Many of the allergens included in the American Contact Dermatitis Society (ACDS) Core 90 Series have alternative chemical aliases, and many have related compounds.⁶ For example, individuals with contact allergy to formaldehyde or a formaldehyde releaser usually need to avoid multiple other formaldehyde-releasing chemicals. Patients who test positive to amidoamine or dimethylaminopropylamine also must avoid the surfactant cocamidopropyl betaine—not because it is a cross-reactor, but because it is an impurity in the synthetic pathway.

Fragrance is one of the most common causes of ACD but can be challenging to avoid. Patients with allergies to fragrance or specific compounds (eg, limonene, linalool hydroperoxides) need to be savvy enough to navigate a broad spectrum of synthetic and botanical fragrance additives. Avoiding products that contain “fragrance” or “parfum” is simple enough, but patients also may need to recognize more than 3000 chemical names to identify individual fragrance ingredients that may be listed separately.⁷ Further, some fragrances are added for alternative purposes—preservative, medicinal, or emulsification—in which case products may deceptively tout themselves as being “fragrance free” yet still contain a fragrance allergen. This is made even more complex considering additional additives that commonly may cross-react with individual fragrance compounds; balsam of Peru, for example, is a botanical amalgam containing more than 250 compounds, including several fragrance components, making it an excellent indicator of fragrance allergy.⁸ While balsam of Peru and its fragrance constituents will almost never be listed on a product label, it cross-reacts with several benzyl derivatives commonly used in cosmetic formulations, such as benzyl alcohol, benzyl acetate, benzoic acid, benzyl benzoate, and benzyl cinnamate.^9,10

Given that ACD is a common reason for patients to seek dermatologic care, it is crucial for clinicians to equip themselves with effective strategies to support patients after patch testing.¹¹ This includes efficient translation of patch test results into practical advice while avoiding the oversimplified suggestion to read product labels; however, education alone cannot address the complexities of managing ACD, which is where contact allergen databases come into play.

An Essential Tool: Patient Allergen Databases and Safe Lists

Contact allergen databases are like a trusty sidekick for patients and clinicians, providing easily accessible information and tools to support allergen avoidance and improve ACD outcomes. While there are several existing resources, the ACDS launched its CAMP database in 2011 for ACDS members and their patients.¹² The CAMP allows clinicians to easily generate personalized safe lists for household, medicament, and personal care products, facilitating seamless patient access both online and via a mobile application. The database also includes allergen-specific handouts to guide patient education.¹³ A key highlight of the CAMP is automated management of cross-reactors, which allows patients to choose products without having to memorize complex cross-reactor algorithms and helps avoid overly restrictive safe lists (Table).^12-15

Other databases and online resources provide similar features, such as resources for patient education or finding safe products. The 2018 Alternatives for Allergens report is a vital adjunctive resource for guiding patients to suitable allergen-free products not included in commonly accessible product databases such as occupational materials, medical adhesives, shoes, or textiles.¹⁶

Introduction of CAMP 2.0

The latest version, CAMP 2.0, was launched in late 2024. The fully revamped database has a catalog of more than 100,000 products and comes packed with features that address many of the limitations found in the original CAMP. How does CAMP 2.0 work? The clinician inputs the patient’s allergens and makes choices about cross-reactor groups, and CAMP 2.0 outputs a list of allergen-free products that the patient can use when shopping for personal care products and the clinician can use for prescribing medicaments. The new user experience is intended to be more informative and engaging for all parties.

The CAMP 2.0 interface offers frequent product updates and streamlined database navigation, including enhanced search functions, barcode scanning, and a new mobile application for Apple and Android users. The mobile application also allows patients to track their symptoms and quality of life over time. With this additional functionality, there also is an extensive section for frequently asked questions and tutorials to help patients understand and utilize these features effectively.

Patients no longer have to wonder if a product that is not listed on their safe list is actually unsafe or just missing from the database. Several new features, including color-coded ingredient lists and organization of search codes into “safe” and “unsafe” product lists (Figure 1), help increase product transparency. These features can facilitate patient recognition of allergen names and cross-reactors in selected products. Future updates will include product purchasing through the mobile application and more educational handouts, including Spanish translations and dietary guidelines for systemic contact dermatitis.

Patient Experience—Once patients complete patch testing with an ACDS member, they can access the CAMP 2.0 database for free via web-based or a mobile application. After setting up an account, patients gain immediate access to their allergen information, product database, and educational resources about ACD and CAMP 2.0. Patients can search for specific products using text or barcode scanning or browse through categorized lists of medical, household, and personal care items. Each product page contains the product name and brand along with a color-coded ingredient list to help patients identify safe and unsafe ingredients at a glance (Figure 1). Products not currently included in the database can be requested using the “Add Product” feature. Additional patient engagement features include options to mark favorite products, write reviews, and track quality of life over time.

Physician Experience—The updated version includes several tutorials and frequently asked questions on how to improve ACD management and make the most of the new CAMP 2.0 tools and features. Generating patient allergen codes has been streamlined with an “Allergen Search” feature, allowing providers to quickly search and add or remove allergens to patients’ safe lists. Cross-reactor groups may be selectively added or removed for greater transparency and specificity in creating a patient safe list (Figure 2). Allergen codes now can be edited over time and are available for patient use via alphanumeric text or QR code format, which easily can be printed on a handout with instructions to help patients get acquainted with the system. For patient counseling, updated education handouts are available in the patient’s app and may be printed to provide supportive written educational material.

Approach to Long-Term Follow-up

When it comes to getting the most from patch testing, ongoing allergen avoidance is crucial. Patients may not see improvement unless they understand what ACD is and what needs to be done to improve it as well as become familiar with the names and common sources of their triggers.¹⁷ Clinicians can use CAMP 2.0 to facilitate patient improvement after patch testing, focusing on 3 key areas: continued patient education, patients’ ongoing progress in avoiding allergens, and monitored clinical improvement.

A solid understanding of ACD, such as its delayed (ie, 24-72 hours) onset after exposure, the need for allergen avoidance for at least 4 to 6 weeks before seeing improvement, and correlation of identified allergens with daily exposures, plays a major role in patient success. The CAMP 2.0 patch testing basics section is an excellent resource for patient-friendly explanations on patch testing and ACD. This resource, as well as allergen education handouts, may be reviewed at follow-up visits to continue to solidify patient learning.

Patients often have questions about allergen avoidance, such as occupational exposures, the suitability of specific products, or specific allergen names. These discussions are helpful for gauging how well patients are equipped to avoid their triggers as well as any hurdles they may be facing. If a patient still is experiencing flares after 6 to 8 weeks of safe-list adherence, it is important to take a thorough history of product use, daily exposures, and the patterns of distribution on the skin. Possible allergen exposures via topical medications also should be considered.^18,19 Cross-checking products with a patient’s CAMP 2.0 safe list and correlating exposures with the continued ACD distribution are effective strategies to troubleshoot for unknown exposures to allergens.

Final Thoughts

Helping patients avoid allergens is essential to long-term management of ACD. The CAMP 2.0 safe list is an essential tool and a comprehensive reference for both patients and clinicians. With CAMP 2.0, allergen avoidance has never been more interactive or accessible.

While patch testing is the gold standard to diagnose type IV cutaneous hypersensitivity reactions, interpreting results can feel like trying to decipher a secret code, leaving patients feeling disempowered in avoiding their triggers. To truly manage allergic contact dermatitis (ACD), patients need comprehensive education on which allergens to avoid and ways to spot potential sources of exposure, including counseling, written guidelines, and lists of product alternatives.¹ Patients who can recall and avoid their triggers experience greater improvement in clinical and quality-of-life scores.² However, several studies have demonstrated that patients have difficulty recalling their allergens, even with longitudinal reminders.^2-5 Quality-of-life and clinical outcomes also are not necessarily improved by successful allergen recall alone, as patients have reported limited success in actually avoiding allergens, highlighting the complexity of navigating exposures in daily life.^2,6 To address these challenges, we examine common pitfalls patients encounter when avoiding allergens, highlight the benefits of utilizing safe lists and databases for allergen management, and introduce the updated Contact Allergen Management Program (CAMP) 2.0 as an optimal tool for long-term management of ACD.

Allergen Avoidance Pitfalls

Simply reading ingredient labels to avoid allergens is only marginally effective, as patients need to identify and interpret multiple chemical names as well as cross-reactors and related compounds to achieve success. Some allergens, such as fragrances or manufacturing impurities, are not explicitly identified on product labels. Even patients who can practice diligent label reading may struggle to find information on household or occupational products when full ingredient disclosure is not required.

Many of the allergens included in the American Contact Dermatitis Society (ACDS) Core 90 Series have alternative chemical aliases, and many have related compounds.⁶ For example, individuals with contact allergy to formaldehyde or a formaldehyde releaser usually need to avoid multiple other formaldehyde-releasing chemicals. Patients who test positive to amidoamine or dimethylaminopropylamine also must avoid the surfactant cocamidopropyl betaine—not because it is a cross-reactor, but because it is an impurity in the synthetic pathway.

Fragrance is one of the most common causes of ACD but can be challenging to avoid. Patients with allergies to fragrance or specific compounds (eg, limonene, linalool hydroperoxides) need to be savvy enough to navigate a broad spectrum of synthetic and botanical fragrance additives. Avoiding products that contain “fragrance” or “parfum” is simple enough, but patients also may need to recognize more than 3000 chemical names to identify individual fragrance ingredients that may be listed separately.⁷ Further, some fragrances are added for alternative purposes—preservative, medicinal, or emulsification—in which case products may deceptively tout themselves as being “fragrance free” yet still contain a fragrance allergen. This is made even more complex considering additional additives that commonly may cross-react with individual fragrance compounds; balsam of Peru, for example, is a botanical amalgam containing more than 250 compounds, including several fragrance components, making it an excellent indicator of fragrance allergy.⁸ While balsam of Peru and its fragrance constituents will almost never be listed on a product label, it cross-reacts with several benzyl derivatives commonly used in cosmetic formulations, such as benzyl alcohol, benzyl acetate, benzoic acid, benzyl benzoate, and benzyl cinnamate.^9,10

Given that ACD is a common reason for patients to seek dermatologic care, it is crucial for clinicians to equip themselves with effective strategies to support patients after patch testing.¹¹ This includes efficient translation of patch test results into practical advice while avoiding the oversimplified suggestion to read product labels; however, education alone cannot address the complexities of managing ACD, which is where contact allergen databases come into play.

An Essential Tool: Patient Allergen Databases and Safe Lists

Contact allergen databases are like a trusty sidekick for patients and clinicians, providing easily accessible information and tools to support allergen avoidance and improve ACD outcomes. While there are several existing resources, the ACDS launched its CAMP database in 2011 for ACDS members and their patients.¹² The CAMP allows clinicians to easily generate personalized safe lists for household, medicament, and personal care products, facilitating seamless patient access both online and via a mobile application. The database also includes allergen-specific handouts to guide patient education.¹³ A key highlight of the CAMP is automated management of cross-reactors, which allows patients to choose products without having to memorize complex cross-reactor algorithms and helps avoid overly restrictive safe lists (Table).^12-15

Other databases and online resources provide similar features, such as resources for patient education or finding safe products. The 2018 Alternatives for Allergens report is a vital adjunctive resource for guiding patients to suitable allergen-free products not included in commonly accessible product databases such as occupational materials, medical adhesives, shoes, or textiles.¹⁶

Introduction of CAMP 2.0

The latest version, CAMP 2.0, was launched in late 2024. The fully revamped database has a catalog of more than 100,000 products and comes packed with features that address many of the limitations found in the original CAMP. How does CAMP 2.0 work? The clinician inputs the patient’s allergens and makes choices about cross-reactor groups, and CAMP 2.0 outputs a list of allergen-free products that the patient can use when shopping for personal care products and the clinician can use for prescribing medicaments. The new user experience is intended to be more informative and engaging for all parties.

The CAMP 2.0 interface offers frequent product updates and streamlined database navigation, including enhanced search functions, barcode scanning, and a new mobile application for Apple and Android users. The mobile application also allows patients to track their symptoms and quality of life over time. With this additional functionality, there also is an extensive section for frequently asked questions and tutorials to help patients understand and utilize these features effectively.

Patients no longer have to wonder if a product that is not listed on their safe list is actually unsafe or just missing from the database. Several new features, including color-coded ingredient lists and organization of search codes into “safe” and “unsafe” product lists (Figure 1), help increase product transparency. These features can facilitate patient recognition of allergen names and cross-reactors in selected products. Future updates will include product purchasing through the mobile application and more educational handouts, including Spanish translations and dietary guidelines for systemic contact dermatitis.

Patient Experience—Once patients complete patch testing with an ACDS member, they can access the CAMP 2.0 database for free via web-based or a mobile application. After setting up an account, patients gain immediate access to their allergen information, product database, and educational resources about ACD and CAMP 2.0. Patients can search for specific products using text or barcode scanning or browse through categorized lists of medical, household, and personal care items. Each product page contains the product name and brand along with a color-coded ingredient list to help patients identify safe and unsafe ingredients at a glance (Figure 1). Products not currently included in the database can be requested using the “Add Product” feature. Additional patient engagement features include options to mark favorite products, write reviews, and track quality of life over time.

Physician Experience—The updated version includes several tutorials and frequently asked questions on how to improve ACD management and make the most of the new CAMP 2.0 tools and features. Generating patient allergen codes has been streamlined with an “Allergen Search” feature, allowing providers to quickly search and add or remove allergens to patients’ safe lists. Cross-reactor groups may be selectively added or removed for greater transparency and specificity in creating a patient safe list (Figure 2). Allergen codes now can be edited over time and are available for patient use via alphanumeric text or QR code format, which easily can be printed on a handout with instructions to help patients get acquainted with the system. For patient counseling, updated education handouts are available in the patient’s app and may be printed to provide supportive written educational material.

Approach to Long-Term Follow-up

When it comes to getting the most from patch testing, ongoing allergen avoidance is crucial. Patients may not see improvement unless they understand what ACD is and what needs to be done to improve it as well as become familiar with the names and common sources of their triggers.¹⁷ Clinicians can use CAMP 2.0 to facilitate patient improvement after patch testing, focusing on 3 key areas: continued patient education, patients’ ongoing progress in avoiding allergens, and monitored clinical improvement.

A solid understanding of ACD, such as its delayed (ie, 24-72 hours) onset after exposure, the need for allergen avoidance for at least 4 to 6 weeks before seeing improvement, and correlation of identified allergens with daily exposures, plays a major role in patient success. The CAMP 2.0 patch testing basics section is an excellent resource for patient-friendly explanations on patch testing and ACD. This resource, as well as allergen education handouts, may be reviewed at follow-up visits to continue to solidify patient learning.

Patients often have questions about allergen avoidance, such as occupational exposures, the suitability of specific products, or specific allergen names. These discussions are helpful for gauging how well patients are equipped to avoid their triggers as well as any hurdles they may be facing. If a patient still is experiencing flares after 6 to 8 weeks of safe-list adherence, it is important to take a thorough history of product use, daily exposures, and the patterns of distribution on the skin. Possible allergen exposures via topical medications also should be considered.^18,19 Cross-checking products with a patient’s CAMP 2.0 safe list and correlating exposures with the continued ACD distribution are effective strategies to troubleshoot for unknown exposures to allergens.

Final Thoughts

Helping patients avoid allergens is essential to long-term management of ACD. The CAMP 2.0 safe list is an essential tool and a comprehensive reference for both patients and clinicians. With CAMP 2.0, allergen avoidance has never been more interactive or accessible.

Practice Gap

Brown macules on the feet can pose diagnostic challenges, often raising suspicion of acral melanoma. Talon noir, which is benign and self-resolving, is characterized by dark patches on the skin of the feet due to hemorrhage within the stratum corneum and commonly is observed in athletes who sustain repetitive foot trauma. In one study, nearly 50% (9/20) of talon noir cases initially were misdiagnosed as acral melanoma or melanocytic nevi.¹ Accurate identification of talon noir is essential to prevent unnecessary interventions or delayed treatment of malignant lesions. Here, we describe a low-risk, cost-effective, and time-efficient diagnostic technique for talon noir using a disposable curette to potentially avoid more invasive procedures.

The Technique

A 34-year-old man presented to the dermatology department with a new brown macule on the second toe. The lesion had been present and stable for more than 4 months, showing no changes in shape or color. The patient reported that he was a frequent runner but did not recall any trauma to the toe, and he denied any associated pain, pruritus, or bleeding. Physical examination revealed a 6-mm dark-brown macule on the hyponychium of the left second toe, with numerous petechiae noted on dermoscopic examination. The findings were consistent with talon noir.

Given the clinical suspicion of talon noir, we used a 5-mm disposable curette to gently pare the superficial epidermis. The superficial curettage effectively removed the lesion, leaving behind a healthy epidermis with no pinpoint bleeding, which confirmed the diagnosis of talon noir (Figure). Pathologic changes from acral melanoma reside deeper than talon noir and consequently cannot be effectively removed by superficial curettage alone. Curettage acts as a curative technique for talon noir, but also as a low-risk, cost-effective, and time-efficient diagnostic technique to rule out insidious diagnoses, including acral melanoma.² A follow-up examination performed several weeks later showed no pigmentation or recurrence of the lesion in our patient, further supporting the diagnosis of talon noir.

Practice Implications

Talon noir refers to localized accumulation of blood within the epidermis due to repetitive trauma, pressure, and shearing forces on the skin that results in pigmented macules.^3-5 Repetitive trauma damages the microvasculature in areas of the skin with minimal subcutaneous adipose tissue.⁶ Talon noir also is known as subcorneal hematoma, intracorneal hematoma, black heel, hyperkeratosis hemorrhagica, and basketball heel.^1,3 First described by Crissey and Peachey³ in 1961 as calcaneal petechiae, the condition was identified in basketball players with well-circumscribed, deep-red lesions on the posterior lateral heels, located between the Achilles tendon insertion and calcaneal fat pad.³ Subsequent reports have documented talon noir in athletes from a range of sports such as tennis and football, whose activities involve rapid directional changes and shearing forces on the feet.⁶ Similar lesions, termed tache noir, have been observed on the hands of athletes including gymnasts, weightlifters, golfers, and climbers due to repetitive hand trauma.⁶ Gross examination reveals blood collecting in the thickened stratum corneum.⁵

The cutaneous manifestations of talon noir can mimic acral melanoma, highlighting the need for dermatologists to understand its clinical, dermoscopic, and microscopic features. Poor patient recall can complicate diagnosis; for instance, in one study only 20% (4/20) of patients remembered the inciting trauma that caused the subcorneal hematomas.¹ Balancing vigilance for melanoma with recognition of more benign conditions such as talon noir—particularly in younger active populations—is essential to minimize patient anxiety and avoid invasive procedures.

Further investigation is warranted in lesions that persist without obvious cause or in those that demonstrate concerning features such as extensive growth. One case of talon noir in a patient with diabetes required an excisional biopsy due to its atypical progression over 1 year with considerable hyperpigmentation and friability.⁷ Additional investigation such as dermoscopy may be required with paring of the skin to establish a diagnosis.¹ Using a curette to pare the thickened stratum corneum, which has no nerve endings, does not require anesthetics.⁸ In talon noir, paring completely removes the lesion, leaving behind unaffected skin, while melanomas would retain their pigmentation due to melanin in the basal layer.²

Talon noir is a benign condition frequently misdiagnosed due to its resemblance to more serious pathologies such as melanoma. Awareness of its clinical and dermoscopic features can promote cost-effective care while reducing unnecessary procedures. Diagnostic paring of the skin with a curette offers a simple and reliable means of distinguishing talon noir from acral melanoma and other potential conditions.

Practice Gap

Brown macules on the feet can pose diagnostic challenges, often raising suspicion of acral melanoma. Talon noir, which is benign and self-resolving, is characterized by dark patches on the skin of the feet due to hemorrhage within the stratum corneum and commonly is observed in athletes who sustain repetitive foot trauma. In one study, nearly 50% (9/20) of talon noir cases initially were misdiagnosed as acral melanoma or melanocytic nevi.¹ Accurate identification of talon noir is essential to prevent unnecessary interventions or delayed treatment of malignant lesions. Here, we describe a low-risk, cost-effective, and time-efficient diagnostic technique for talon noir using a disposable curette to potentially avoid more invasive procedures.

The Technique

A 34-year-old man presented to the dermatology department with a new brown macule on the second toe. The lesion had been present and stable for more than 4 months, showing no changes in shape or color. The patient reported that he was a frequent runner but did not recall any trauma to the toe, and he denied any associated pain, pruritus, or bleeding. Physical examination revealed a 6-mm dark-brown macule on the hyponychium of the left second toe, with numerous petechiae noted on dermoscopic examination. The findings were consistent with talon noir.

Given the clinical suspicion of talon noir, we used a 5-mm disposable curette to gently pare the superficial epidermis. The superficial curettage effectively removed the lesion, leaving behind a healthy epidermis with no pinpoint bleeding, which confirmed the diagnosis of talon noir (Figure). Pathologic changes from acral melanoma reside deeper than talon noir and consequently cannot be effectively removed by superficial curettage alone. Curettage acts as a curative technique for talon noir, but also as a low-risk, cost-effective, and time-efficient diagnostic technique to rule out insidious diagnoses, including acral melanoma.² A follow-up examination performed several weeks later showed no pigmentation or recurrence of the lesion in our patient, further supporting the diagnosis of talon noir.

Practice Implications

Talon noir refers to localized accumulation of blood within the epidermis due to repetitive trauma, pressure, and shearing forces on the skin that results in pigmented macules.^3-5 Repetitive trauma damages the microvasculature in areas of the skin with minimal subcutaneous adipose tissue.⁶ Talon noir also is known as subcorneal hematoma, intracorneal hematoma, black heel, hyperkeratosis hemorrhagica, and basketball heel.^1,3 First described by Crissey and Peachey³ in 1961 as calcaneal petechiae, the condition was identified in basketball players with well-circumscribed, deep-red lesions on the posterior lateral heels, located between the Achilles tendon insertion and calcaneal fat pad.³ Subsequent reports have documented talon noir in athletes from a range of sports such as tennis and football, whose activities involve rapid directional changes and shearing forces on the feet.⁶ Similar lesions, termed tache noir, have been observed on the hands of athletes including gymnasts, weightlifters, golfers, and climbers due to repetitive hand trauma.⁶ Gross examination reveals blood collecting in the thickened stratum corneum.⁵

The cutaneous manifestations of talon noir can mimic acral melanoma, highlighting the need for dermatologists to understand its clinical, dermoscopic, and microscopic features. Poor patient recall can complicate diagnosis; for instance, in one study only 20% (4/20) of patients remembered the inciting trauma that caused the subcorneal hematomas.¹ Balancing vigilance for melanoma with recognition of more benign conditions such as talon noir—particularly in younger active populations—is essential to minimize patient anxiety and avoid invasive procedures.

Further investigation is warranted in lesions that persist without obvious cause or in those that demonstrate concerning features such as extensive growth. One case of talon noir in a patient with diabetes required an excisional biopsy due to its atypical progression over 1 year with considerable hyperpigmentation and friability.⁷ Additional investigation such as dermoscopy may be required with paring of the skin to establish a diagnosis.¹ Using a curette to pare the thickened stratum corneum, which has no nerve endings, does not require anesthetics.⁸ In talon noir, paring completely removes the lesion, leaving behind unaffected skin, while melanomas would retain their pigmentation due to melanin in the basal layer.²

Talon noir is a benign condition frequently misdiagnosed due to its resemblance to more serious pathologies such as melanoma. Awareness of its clinical and dermoscopic features can promote cost-effective care while reducing unnecessary procedures. Diagnostic paring of the skin with a curette offers a simple and reliable means of distinguishing talon noir from acral melanoma and other potential conditions.

Practice Gap

Brown macules on the feet can pose diagnostic challenges, often raising suspicion of acral melanoma. Talon noir, which is benign and self-resolving, is characterized by dark patches on the skin of the feet due to hemorrhage within the stratum corneum and commonly is observed in athletes who sustain repetitive foot trauma. In one study, nearly 50% (9/20) of talon noir cases initially were misdiagnosed as acral melanoma or melanocytic nevi.¹ Accurate identification of talon noir is essential to prevent unnecessary interventions or delayed treatment of malignant lesions. Here, we describe a low-risk, cost-effective, and time-efficient diagnostic technique for talon noir using a disposable curette to potentially avoid more invasive procedures.

The Technique

A 34-year-old man presented to the dermatology department with a new brown macule on the second toe. The lesion had been present and stable for more than 4 months, showing no changes in shape or color. The patient reported that he was a frequent runner but did not recall any trauma to the toe, and he denied any associated pain, pruritus, or bleeding. Physical examination revealed a 6-mm dark-brown macule on the hyponychium of the left second toe, with numerous petechiae noted on dermoscopic examination. The findings were consistent with talon noir.

Given the clinical suspicion of talon noir, we used a 5-mm disposable curette to gently pare the superficial epidermis. The superficial curettage effectively removed the lesion, leaving behind a healthy epidermis with no pinpoint bleeding, which confirmed the diagnosis of talon noir (Figure). Pathologic changes from acral melanoma reside deeper than talon noir and consequently cannot be effectively removed by superficial curettage alone. Curettage acts as a curative technique for talon noir, but also as a low-risk, cost-effective, and time-efficient diagnostic technique to rule out insidious diagnoses, including acral melanoma.² A follow-up examination performed several weeks later showed no pigmentation or recurrence of the lesion in our patient, further supporting the diagnosis of talon noir.

Practice Implications

Talon noir refers to localized accumulation of blood within the epidermis due to repetitive trauma, pressure, and shearing forces on the skin that results in pigmented macules.^3-5 Repetitive trauma damages the microvasculature in areas of the skin with minimal subcutaneous adipose tissue.⁶ Talon noir also is known as subcorneal hematoma, intracorneal hematoma, black heel, hyperkeratosis hemorrhagica, and basketball heel.^1,3 First described by Crissey and Peachey³ in 1961 as calcaneal petechiae, the condition was identified in basketball players with well-circumscribed, deep-red lesions on the posterior lateral heels, located between the Achilles tendon insertion and calcaneal fat pad.³ Subsequent reports have documented talon noir in athletes from a range of sports such as tennis and football, whose activities involve rapid directional changes and shearing forces on the feet.⁶ Similar lesions, termed tache noir, have been observed on the hands of athletes including gymnasts, weightlifters, golfers, and climbers due to repetitive hand trauma.⁶ Gross examination reveals blood collecting in the thickened stratum corneum.⁵

The cutaneous manifestations of talon noir can mimic acral melanoma, highlighting the need for dermatologists to understand its clinical, dermoscopic, and microscopic features. Poor patient recall can complicate diagnosis; for instance, in one study only 20% (4/20) of patients remembered the inciting trauma that caused the subcorneal hematomas.¹ Balancing vigilance for melanoma with recognition of more benign conditions such as talon noir—particularly in younger active populations—is essential to minimize patient anxiety and avoid invasive procedures.

Further investigation is warranted in lesions that persist without obvious cause or in those that demonstrate concerning features such as extensive growth. One case of talon noir in a patient with diabetes required an excisional biopsy due to its atypical progression over 1 year with considerable hyperpigmentation and friability.⁷ Additional investigation such as dermoscopy may be required with paring of the skin to establish a diagnosis.¹ Using a curette to pare the thickened stratum corneum, which has no nerve endings, does not require anesthetics.⁸ In talon noir, paring completely removes the lesion, leaving behind unaffected skin, while melanomas would retain their pigmentation due to melanin in the basal layer.²

Talon noir is a benign condition frequently misdiagnosed due to its resemblance to more serious pathologies such as melanoma. Awareness of its clinical and dermoscopic features can promote cost-effective care while reducing unnecessary procedures. Diagnostic paring of the skin with a curette offers a simple and reliable means of distinguishing talon noir from acral melanoma and other potential conditions.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful recurrent abscesses. Several autoimmune and endocrine diseases are associated with HS, including inflammatory bowel disease and diabetes mellitus (DM).¹ Notably, the association between HS and thyroid disorders is poorly characterized,² and there are no known nationwide studies exploring this potential association in the hospital setting. In this cross-sectional matched cohort study, we aimed to characterize HS patients with comorbid thyroid disorders as well as to explore whether thyroid disease is associated with comorbidities and hospital outcome measures in these patients.

The 2019 National Inpatient Sample (NIS) was weighted in accordance with NIS-assigned weight variables and queried for HS, hypothyroidism, and hyperthyroidism cases using International Classification of Diseases, Tenth Revision, codes L73.2, E03, and E05, respectively. Propensity score matching based on age and sex was performed using a nearest-neighbor method in the MatchIt statistical R package. Patient demographics, comorbidities, and outcome variables were collected. Univariable analysis of HS patients with thyroid disease vs those without thyroid disease vs controls without HS were performed using X² and t-test functions in SPSS statistical software (IBM). A series of multivariate analyses were performed using SPSS logistic and linear regression models to examine the effect of thyroid disease on hospital outcome measures and comorbidities in HS patients, with statistical significance set at P=.05.

A total of 1720 HS patients with comorbid thyroid disease (hyperthyroidism/hypothyroidism), 23,785 HS patients without thyroid disease, and 25,497 age- and sex-matched controls were included in the analysis. On average, HS patients with comorbid thyroid disease were older than HS patients without thyroid disease and controls (49.36 years vs 42.17 years vs 42.66 years [P<.001]), more likely to be female (75.58% vs 58.67% vs 59.81% [P<.001]), more likely to be in the highest income quartile (17.52% vs 12.18% vs 8.14% [P<.001]), and more likely to be Medicare insured (39.07% vs 27.47% vs 18.02% [P<.001])(eTable).

On univariate analysis of hospital outcome measures, HS patients with comorbid thyroid disease had the highest frequency of extreme likelihood of dying compared with HS patients without thyroid disease and with controls (6.40% vs 5.38% vs 2.47% [P<.001]), the highest mean number of diagnoses (18.31 vs 14.14 vs 8.57 [P<.001]), and the longest mean length of hospital stay (6.03 days vs 5.94 days vs 3.73 days [P<.001]). On univariate analysis of comorbidities, HS patients with thyroid disease had the highest incidence of the following comorbidities compared with HS patients without thyroid disease and controls: hypertension (34.01% vs 28.55% vs 22.39% [P<.001]), DM (48.26% vs 35.63% vs 18.05% [P<.001]), obesity (46.80% vs 39.65% vs 11.70% [P<.001]), and acute kidney injury (AKI)(21.80% vs 13.10% vs 6.33% [P<.001])(eTable).

A multivariate analysis adjusting for multiple potential confounders including age, sex, race, median income quartile, disposition/discharge location, and primary payer was performed for hospital outcome measures and comorbidities. There were no significant differences in hospital outcome measures between HS patients with comorbid thyroid disease vs those without thyroid disease (P>.05)(Table 1). Thyroid disease was associated with increased odds of comorbid DM (odds ratio [OR], 1.242 [95% CI, 1.113-1.386]), obesity (OR, 1.173 [95% CI, 1.057-1.302]), and AKI (OR, 1.623 [95% CI, 1.423-1.851]) and decreased odds of comorbid nicotine dependence (OR, 0.609 [95% CI, 0.540-0.687]), skin and soft tissue infections (OR, 0.712 [95% CI, 0.637-0.797]), and sepsis (OR, 0.836 [95% CI, 0.717-0.973]) in HS patients (Table 2).

We found that HS patients with thyroid disease had increased odds of comorbid obesity, DM, and AKI compared with HS patients without thyroid disease when adjusting for potential confounders on multivariate analysis. A 2019 nationwide cross-sectional study of 18,224 patients with thyroid disease and 72,896 controls in Taiwan showed a higher prevalence of obesity (1.26% vs 0.57% [P<.0001]) and a higher hazard ratio (HR) of type 2 DM (HR, 1.23 [95% CI, 1.16-1.31]) in the thyroid disease group vs the controls.³ In a 2024 claims-based national cohort study of 4,152,830 patients with 2 or more consecutive thyroid-stimulating hormone measurements in the United States, patients with hypothyroidism and hyperthyroidism had a higher incidence risk for kidney dysfunction vs patients with euthyroidism (HRs, 1.37 [95% CI, 1.34–1.40] and 1.42 [95% CI, 1.39-1.45]).⁴ In addition, patients with and without DM and thyroid disease had increased risk for kidney disease compared to patients with and without DM and euthyroidism (hypothyroidism: HRs, 1.17 [95% CI, 1.13-1.22] and 1.52 [95% CI, 1.49-1.56]; hyperthyroidism: HRs, 1.34 [95% CI, 1.29-1.38] and 1.36 [95% CI, 1.33-1.39]). Furthermore, patients with and without obesity and thyroid disease had increased risk for kidney disease compared to patients with and without obesity and with euthyroidism (hypothyroidism: HRs, 1.40 [95% CI, 1.36-1.45] and 1.26 [95% CI, 1.21-1.32]; hyperthyroidism: HRs, 1.34 [95% CI, 1.30-1.39] and 1.35 [95% CI, 1.30-1.40]).⁴ However, these studies did not focus on HS patients.⁵

Hidradenitis suppurativa has a major comorbidity burden, including obesity, DM, and kidney disease.⁵ Our findings suggest a potential additive risk for these conditions in HS patients with comorbid thyroid disease; therefore, heightened surveillance for obesity, DM, and AKI in this population is encouraged. Prospective and retrospective studies in HS patients assessing the risk for each comorbidity while controlling for the others may help to better characterize these relationships.

Using multivariate analysis, we found that HS patients with comorbid thyroid disease had no significant differences in hospital outcome measures compared with HS patients without thyroid disease despite significant differences on univariate analysis (P<.05). Similarly, in a 2018 cross-sectional study of 430 HS patients and 20,780 controls in Denmark, the HS group had 10% lower thyroid-stimulating hormone levels vs the control group, but this did not significantly affect HS severity and thyroid function on multivariate analysis.⁶ In a 2020 cross-sectional analysis of 290 Greek HS patients, thyroid disease was associated with higher HS severity using Hurley classification (OR, 1.19 [95% CI, 1.03-1.51]) and International Hidradenitis Suppurativa Severity Score System 4 classification (OR, 1.29 [95% CI, 1.13-1.62]); however, this analysis was univariate and did not account for confounders.⁷ Taken together, our study and previous research suggest that thyroid disease is not an independent prognostic indicator for hospital outcome measures in HS patients when cofounders are considered and therefore may not warrant extra caution when treating hospitalized HS patients.

Nicotine dependence was an important potential confounder with regard to the effects of comorbid thyroid disease on outcomes of HS patients in our study. While we found that the prevalence of nicotine dependence was higher in HS patients vs matched controls, HS patients with comorbid thyroid disease had a lower prevalence of nicotine dependence than HS patients without thyroid disease. Furthermore, thyroid disease was associated with decreased odds of nicotine dependence in HS patients when adjusting for confounders. Previous studies have shown an association between cigarette smoking and HS. Smoking also may affect thyroid function via thiocyanate, sympathetic activation, or immunologic disturbances. Smoking may have both prothyroid and antithyroid effects.⁶ In a 2023 cross-sectional study of 108 HS patients and 52 age- and sex-matched controls in Germany, HS patients had higher thyroid antibody (TRAb) levels compared with controls (median TRAb level, 15.4 vs 14.2 [P=.026]), with even greater increases in TRAb in HS patients who were smokers or former smokers vs never smokers (median TRAb level, 1.18 vs 1.08 [P=.042]).²

There was a lower frequency of thyroid disease in our HS cohort compared with our matched controls cohort. While there are conflicting reports on the association between HS and thyroid disease in the literature, 2 recent meta-analyses of 5 and 6 case-control studies, respectively, found an association between HS and thyroid disease (OR, 1.36 [95% CI, 1.13-1.64] and 1.88 [95% CI, 1.25-2.81]).^1,8 Notably, these studies were either claims or survey based, included outpatients, or were unspecified. One potential explanation for the difference in our findings vs those of other studies could be underdiagnosis of thyroid disease in hospitalized HS patients. We found that HS patients were most frequently Medicaid or Medicare insured compared to controls, who most frequently were privately insured. Increased availability and ease of access to outpatient medical care through private health insurance may be a possible contributor to the higher frequency of diagnosed thyroid disease in control patients in our study; therefore, awareness of potential underdiagnosis of thyroid disease in hospitalized HS patients is recommended.

Limitations of our study included those inherent to the NIS database, including potential miscoding and lack of data on pharmacologic treatments. Outcome measures assessed were limited by inclusion of both primary and secondary diagnoses of HS and thyroid disease in our cohort and may have been affected by other conditions. As with any observational study, there was a possibility of unidentified confounders unaccounted for in our study.

In conclusion, in this national inpatient-matched cohort study, thyroid disease was associated with increased odds of obesity, DM, and AKI in HS inpatients but was not an independent risk factor for worse hospital outcome measures. Therefore, while increased surveillance of associated comorbidities is appropriate, thyroid disease may not be a cause for increased concern for dermatologists treating hospitalized HS patients. Prospective studies are necessary to better characterize these findings.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful recurrent abscesses. Several autoimmune and endocrine diseases are associated with HS, including inflammatory bowel disease and diabetes mellitus (DM).¹ Notably, the association between HS and thyroid disorders is poorly characterized,² and there are no known nationwide studies exploring this potential association in the hospital setting. In this cross-sectional matched cohort study, we aimed to characterize HS patients with comorbid thyroid disorders as well as to explore whether thyroid disease is associated with comorbidities and hospital outcome measures in these patients.

The 2019 National Inpatient Sample (NIS) was weighted in accordance with NIS-assigned weight variables and queried for HS, hypothyroidism, and hyperthyroidism cases using International Classification of Diseases, Tenth Revision, codes L73.2, E03, and E05, respectively. Propensity score matching based on age and sex was performed using a nearest-neighbor method in the MatchIt statistical R package. Patient demographics, comorbidities, and outcome variables were collected. Univariable analysis of HS patients with thyroid disease vs those without thyroid disease vs controls without HS were performed using X² and t-test functions in SPSS statistical software (IBM). A series of multivariate analyses were performed using SPSS logistic and linear regression models to examine the effect of thyroid disease on hospital outcome measures and comorbidities in HS patients, with statistical significance set at P=.05.

A total of 1720 HS patients with comorbid thyroid disease (hyperthyroidism/hypothyroidism), 23,785 HS patients without thyroid disease, and 25,497 age- and sex-matched controls were included in the analysis. On average, HS patients with comorbid thyroid disease were older than HS patients without thyroid disease and controls (49.36 years vs 42.17 years vs 42.66 years [P<.001]), more likely to be female (75.58% vs 58.67% vs 59.81% [P<.001]), more likely to be in the highest income quartile (17.52% vs 12.18% vs 8.14% [P<.001]), and more likely to be Medicare insured (39.07% vs 27.47% vs 18.02% [P<.001])(eTable).

On univariate analysis of hospital outcome measures, HS patients with comorbid thyroid disease had the highest frequency of extreme likelihood of dying compared with HS patients without thyroid disease and with controls (6.40% vs 5.38% vs 2.47% [P<.001]), the highest mean number of diagnoses (18.31 vs 14.14 vs 8.57 [P<.001]), and the longest mean length of hospital stay (6.03 days vs 5.94 days vs 3.73 days [P<.001]). On univariate analysis of comorbidities, HS patients with thyroid disease had the highest incidence of the following comorbidities compared with HS patients without thyroid disease and controls: hypertension (34.01% vs 28.55% vs 22.39% [P<.001]), DM (48.26% vs 35.63% vs 18.05% [P<.001]), obesity (46.80% vs 39.65% vs 11.70% [P<.001]), and acute kidney injury (AKI)(21.80% vs 13.10% vs 6.33% [P<.001])(eTable).

A multivariate analysis adjusting for multiple potential confounders including age, sex, race, median income quartile, disposition/discharge location, and primary payer was performed for hospital outcome measures and comorbidities. There were no significant differences in hospital outcome measures between HS patients with comorbid thyroid disease vs those without thyroid disease (P>.05)(Table 1). Thyroid disease was associated with increased odds of comorbid DM (odds ratio [OR], 1.242 [95% CI, 1.113-1.386]), obesity (OR, 1.173 [95% CI, 1.057-1.302]), and AKI (OR, 1.623 [95% CI, 1.423-1.851]) and decreased odds of comorbid nicotine dependence (OR, 0.609 [95% CI, 0.540-0.687]), skin and soft tissue infections (OR, 0.712 [95% CI, 0.637-0.797]), and sepsis (OR, 0.836 [95% CI, 0.717-0.973]) in HS patients (Table 2).

We found that HS patients with thyroid disease had increased odds of comorbid obesity, DM, and AKI compared with HS patients without thyroid disease when adjusting for potential confounders on multivariate analysis. A 2019 nationwide cross-sectional study of 18,224 patients with thyroid disease and 72,896 controls in Taiwan showed a higher prevalence of obesity (1.26% vs 0.57% [P<.0001]) and a higher hazard ratio (HR) of type 2 DM (HR, 1.23 [95% CI, 1.16-1.31]) in the thyroid disease group vs the controls.³ In a 2024 claims-based national cohort study of 4,152,830 patients with 2 or more consecutive thyroid-stimulating hormone measurements in the United States, patients with hypothyroidism and hyperthyroidism had a higher incidence risk for kidney dysfunction vs patients with euthyroidism (HRs, 1.37 [95% CI, 1.34–1.40] and 1.42 [95% CI, 1.39-1.45]).⁴ In addition, patients with and without DM and thyroid disease had increased risk for kidney disease compared to patients with and without DM and euthyroidism (hypothyroidism: HRs, 1.17 [95% CI, 1.13-1.22] and 1.52 [95% CI, 1.49-1.56]; hyperthyroidism: HRs, 1.34 [95% CI, 1.29-1.38] and 1.36 [95% CI, 1.33-1.39]). Furthermore, patients with and without obesity and thyroid disease had increased risk for kidney disease compared to patients with and without obesity and with euthyroidism (hypothyroidism: HRs, 1.40 [95% CI, 1.36-1.45] and 1.26 [95% CI, 1.21-1.32]; hyperthyroidism: HRs, 1.34 [95% CI, 1.30-1.39] and 1.35 [95% CI, 1.30-1.40]).⁴ However, these studies did not focus on HS patients.⁵

Hidradenitis suppurativa has a major comorbidity burden, including obesity, DM, and kidney disease.⁵ Our findings suggest a potential additive risk for these conditions in HS patients with comorbid thyroid disease; therefore, heightened surveillance for obesity, DM, and AKI in this population is encouraged. Prospective and retrospective studies in HS patients assessing the risk for each comorbidity while controlling for the others may help to better characterize these relationships.

Using multivariate analysis, we found that HS patients with comorbid thyroid disease had no significant differences in hospital outcome measures compared with HS patients without thyroid disease despite significant differences on univariate analysis (P<.05). Similarly, in a 2018 cross-sectional study of 430 HS patients and 20,780 controls in Denmark, the HS group had 10% lower thyroid-stimulating hormone levels vs the control group, but this did not significantly affect HS severity and thyroid function on multivariate analysis.⁶ In a 2020 cross-sectional analysis of 290 Greek HS patients, thyroid disease was associated with higher HS severity using Hurley classification (OR, 1.19 [95% CI, 1.03-1.51]) and International Hidradenitis Suppurativa Severity Score System 4 classification (OR, 1.29 [95% CI, 1.13-1.62]); however, this analysis was univariate and did not account for confounders.⁷ Taken together, our study and previous research suggest that thyroid disease is not an independent prognostic indicator for hospital outcome measures in HS patients when cofounders are considered and therefore may not warrant extra caution when treating hospitalized HS patients.

Nicotine dependence was an important potential confounder with regard to the effects of comorbid thyroid disease on outcomes of HS patients in our study. While we found that the prevalence of nicotine dependence was higher in HS patients vs matched controls, HS patients with comorbid thyroid disease had a lower prevalence of nicotine dependence than HS patients without thyroid disease. Furthermore, thyroid disease was associated with decreased odds of nicotine dependence in HS patients when adjusting for confounders. Previous studies have shown an association between cigarette smoking and HS. Smoking also may affect thyroid function via thiocyanate, sympathetic activation, or immunologic disturbances. Smoking may have both prothyroid and antithyroid effects.⁶ In a 2023 cross-sectional study of 108 HS patients and 52 age- and sex-matched controls in Germany, HS patients had higher thyroid antibody (TRAb) levels compared with controls (median TRAb level, 15.4 vs 14.2 [P=.026]), with even greater increases in TRAb in HS patients who were smokers or former smokers vs never smokers (median TRAb level, 1.18 vs 1.08 [P=.042]).²

There was a lower frequency of thyroid disease in our HS cohort compared with our matched controls cohort. While there are conflicting reports on the association between HS and thyroid disease in the literature, 2 recent meta-analyses of 5 and 6 case-control studies, respectively, found an association between HS and thyroid disease (OR, 1.36 [95% CI, 1.13-1.64] and 1.88 [95% CI, 1.25-2.81]).^1,8 Notably, these studies were either claims or survey based, included outpatients, or were unspecified. One potential explanation for the difference in our findings vs those of other studies could be underdiagnosis of thyroid disease in hospitalized HS patients. We found that HS patients were most frequently Medicaid or Medicare insured compared to controls, who most frequently were privately insured. Increased availability and ease of access to outpatient medical care through private health insurance may be a possible contributor to the higher frequency of diagnosed thyroid disease in control patients in our study; therefore, awareness of potential underdiagnosis of thyroid disease in hospitalized HS patients is recommended.

Limitations of our study included those inherent to the NIS database, including potential miscoding and lack of data on pharmacologic treatments. Outcome measures assessed were limited by inclusion of both primary and secondary diagnoses of HS and thyroid disease in our cohort and may have been affected by other conditions. As with any observational study, there was a possibility of unidentified confounders unaccounted for in our study.

In conclusion, in this national inpatient-matched cohort study, thyroid disease was associated with increased odds of obesity, DM, and AKI in HS inpatients but was not an independent risk factor for worse hospital outcome measures. Therefore, while increased surveillance of associated comorbidities is appropriate, thyroid disease may not be a cause for increased concern for dermatologists treating hospitalized HS patients. Prospective studies are necessary to better characterize these findings.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful recurrent abscesses. Several autoimmune and endocrine diseases are associated with HS, including inflammatory bowel disease and diabetes mellitus (DM).¹ Notably, the association between HS and thyroid disorders is poorly characterized,² and there are no known nationwide studies exploring this potential association in the hospital setting. In this cross-sectional matched cohort study, we aimed to characterize HS patients with comorbid thyroid disorders as well as to explore whether thyroid disease is associated with comorbidities and hospital outcome measures in these patients.

The 2019 National Inpatient Sample (NIS) was weighted in accordance with NIS-assigned weight variables and queried for HS, hypothyroidism, and hyperthyroidism cases using International Classification of Diseases, Tenth Revision, codes L73.2, E03, and E05, respectively. Propensity score matching based on age and sex was performed using a nearest-neighbor method in the MatchIt statistical R package. Patient demographics, comorbidities, and outcome variables were collected. Univariable analysis of HS patients with thyroid disease vs those without thyroid disease vs controls without HS were performed using X² and t-test functions in SPSS statistical software (IBM). A series of multivariate analyses were performed using SPSS logistic and linear regression models to examine the effect of thyroid disease on hospital outcome measures and comorbidities in HS patients, with statistical significance set at P=.05.

A total of 1720 HS patients with comorbid thyroid disease (hyperthyroidism/hypothyroidism), 23,785 HS patients without thyroid disease, and 25,497 age- and sex-matched controls were included in the analysis. On average, HS patients with comorbid thyroid disease were older than HS patients without thyroid disease and controls (49.36 years vs 42.17 years vs 42.66 years [P<.001]), more likely to be female (75.58% vs 58.67% vs 59.81% [P<.001]), more likely to be in the highest income quartile (17.52% vs 12.18% vs 8.14% [P<.001]), and more likely to be Medicare insured (39.07% vs 27.47% vs 18.02% [P<.001])(eTable).

On univariate analysis of hospital outcome measures, HS patients with comorbid thyroid disease had the highest frequency of extreme likelihood of dying compared with HS patients without thyroid disease and with controls (6.40% vs 5.38% vs 2.47% [P<.001]), the highest mean number of diagnoses (18.31 vs 14.14 vs 8.57 [P<.001]), and the longest mean length of hospital stay (6.03 days vs 5.94 days vs 3.73 days [P<.001]). On univariate analysis of comorbidities, HS patients with thyroid disease had the highest incidence of the following comorbidities compared with HS patients without thyroid disease and controls: hypertension (34.01% vs 28.55% vs 22.39% [P<.001]), DM (48.26% vs 35.63% vs 18.05% [P<.001]), obesity (46.80% vs 39.65% vs 11.70% [P<.001]), and acute kidney injury (AKI)(21.80% vs 13.10% vs 6.33% [P<.001])(eTable).

A multivariate analysis adjusting for multiple potential confounders including age, sex, race, median income quartile, disposition/discharge location, and primary payer was performed for hospital outcome measures and comorbidities. There were no significant differences in hospital outcome measures between HS patients with comorbid thyroid disease vs those without thyroid disease (P>.05)(Table 1). Thyroid disease was associated with increased odds of comorbid DM (odds ratio [OR], 1.242 [95% CI, 1.113-1.386]), obesity (OR, 1.173 [95% CI, 1.057-1.302]), and AKI (OR, 1.623 [95% CI, 1.423-1.851]) and decreased odds of comorbid nicotine dependence (OR, 0.609 [95% CI, 0.540-0.687]), skin and soft tissue infections (OR, 0.712 [95% CI, 0.637-0.797]), and sepsis (OR, 0.836 [95% CI, 0.717-0.973]) in HS patients (Table 2).

We found that HS patients with thyroid disease had increased odds of comorbid obesity, DM, and AKI compared with HS patients without thyroid disease when adjusting for potential confounders on multivariate analysis. A 2019 nationwide cross-sectional study of 18,224 patients with thyroid disease and 72,896 controls in Taiwan showed a higher prevalence of obesity (1.26% vs 0.57% [P<.0001]) and a higher hazard ratio (HR) of type 2 DM (HR, 1.23 [95% CI, 1.16-1.31]) in the thyroid disease group vs the controls.³ In a 2024 claims-based national cohort study of 4,152,830 patients with 2 or more consecutive thyroid-stimulating hormone measurements in the United States, patients with hypothyroidism and hyperthyroidism had a higher incidence risk for kidney dysfunction vs patients with euthyroidism (HRs, 1.37 [95% CI, 1.34–1.40] and 1.42 [95% CI, 1.39-1.45]).⁴ In addition, patients with and without DM and thyroid disease had increased risk for kidney disease compared to patients with and without DM and euthyroidism (hypothyroidism: HRs, 1.17 [95% CI, 1.13-1.22] and 1.52 [95% CI, 1.49-1.56]; hyperthyroidism: HRs, 1.34 [95% CI, 1.29-1.38] and 1.36 [95% CI, 1.33-1.39]). Furthermore, patients with and without obesity and thyroid disease had increased risk for kidney disease compared to patients with and without obesity and with euthyroidism (hypothyroidism: HRs, 1.40 [95% CI, 1.36-1.45] and 1.26 [95% CI, 1.21-1.32]; hyperthyroidism: HRs, 1.34 [95% CI, 1.30-1.39] and 1.35 [95% CI, 1.30-1.40]).⁴ However, these studies did not focus on HS patients.⁵

Hidradenitis suppurativa has a major comorbidity burden, including obesity, DM, and kidney disease.⁵ Our findings suggest a potential additive risk for these conditions in HS patients with comorbid thyroid disease; therefore, heightened surveillance for obesity, DM, and AKI in this population is encouraged. Prospective and retrospective studies in HS patients assessing the risk for each comorbidity while controlling for the others may help to better characterize these relationships.

Using multivariate analysis, we found that HS patients with comorbid thyroid disease had no significant differences in hospital outcome measures compared with HS patients without thyroid disease despite significant differences on univariate analysis (P<.05). Similarly, in a 2018 cross-sectional study of 430 HS patients and 20,780 controls in Denmark, the HS group had 10% lower thyroid-stimulating hormone levels vs the control group, but this did not significantly affect HS severity and thyroid function on multivariate analysis.⁶ In a 2020 cross-sectional analysis of 290 Greek HS patients, thyroid disease was associated with higher HS severity using Hurley classification (OR, 1.19 [95% CI, 1.03-1.51]) and International Hidradenitis Suppurativa Severity Score System 4 classification (OR, 1.29 [95% CI, 1.13-1.62]); however, this analysis was univariate and did not account for confounders.⁷ Taken together, our study and previous research suggest that thyroid disease is not an independent prognostic indicator for hospital outcome measures in HS patients when cofounders are considered and therefore may not warrant extra caution when treating hospitalized HS patients.

Nicotine dependence was an important potential confounder with regard to the effects of comorbid thyroid disease on outcomes of HS patients in our study. While we found that the prevalence of nicotine dependence was higher in HS patients vs matched controls, HS patients with comorbid thyroid disease had a lower prevalence of nicotine dependence than HS patients without thyroid disease. Furthermore, thyroid disease was associated with decreased odds of nicotine dependence in HS patients when adjusting for confounders. Previous studies have shown an association between cigarette smoking and HS. Smoking also may affect thyroid function via thiocyanate, sympathetic activation, or immunologic disturbances. Smoking may have both prothyroid and antithyroid effects.⁶ In a 2023 cross-sectional study of 108 HS patients and 52 age- and sex-matched controls in Germany, HS patients had higher thyroid antibody (TRAb) levels compared with controls (median TRAb level, 15.4 vs 14.2 [P=.026]), with even greater increases in TRAb in HS patients who were smokers or former smokers vs never smokers (median TRAb level, 1.18 vs 1.08 [P=.042]).²

There was a lower frequency of thyroid disease in our HS cohort compared with our matched controls cohort. While there are conflicting reports on the association between HS and thyroid disease in the literature, 2 recent meta-analyses of 5 and 6 case-control studies, respectively, found an association between HS and thyroid disease (OR, 1.36 [95% CI, 1.13-1.64] and 1.88 [95% CI, 1.25-2.81]).^1,8 Notably, these studies were either claims or survey based, included outpatients, or were unspecified. One potential explanation for the difference in our findings vs those of other studies could be underdiagnosis of thyroid disease in hospitalized HS patients. We found that HS patients were most frequently Medicaid or Medicare insured compared to controls, who most frequently were privately insured. Increased availability and ease of access to outpatient medical care through private health insurance may be a possible contributor to the higher frequency of diagnosed thyroid disease in control patients in our study; therefore, awareness of potential underdiagnosis of thyroid disease in hospitalized HS patients is recommended.

Limitations of our study included those inherent to the NIS database, including potential miscoding and lack of data on pharmacologic treatments. Outcome measures assessed were limited by inclusion of both primary and secondary diagnoses of HS and thyroid disease in our cohort and may have been affected by other conditions. As with any observational study, there was a possibility of unidentified confounders unaccounted for in our study.

In conclusion, in this national inpatient-matched cohort study, thyroid disease was associated with increased odds of obesity, DM, and AKI in HS inpatients but was not an independent risk factor for worse hospital outcome measures. Therefore, while increased surveillance of associated comorbidities is appropriate, thyroid disease may not be a cause for increased concern for dermatologists treating hospitalized HS patients. Prospective studies are necessary to better characterize these findings.

Spironolactone is an aldosterone antagonist that first was used as a potassium-sparing diuretic to treat heart failure and hypertension. It also possesses antiandrogenic mechanisms including competitively inhibiting androgen receptors, increasing steroid hormone–binding globulin production, and decreasing 5α-reductase activity.¹ These properties have been leveraged in off-label use for dermatologic conditions including acne, hidradenitis suppurativa, androgenic alopecia, and hirsutism.^1,2 Despite being used off-label to treat acne for more than 40 years, spironolactone has not received US Food and Drug Administration approval for this indication.³ Herein, we review the current evidence for use of spironolactone in acne management.

Spironolactone Efficacy

Spironolactone is efficacious for facial and truncal acne in adult females; it cannot be used in males given its anti-androgenic effects.^4,5 In 2 large studies, spironolactone completely or partially cleared facial acne in 75.5% to 85.1% of patients.^4,5 In the first study, which included 395 patients on a median dose of 100 mg/d (range, 25-200 mg/d), clearance of comedonal, papulopustular, and nodulocystic acne was observed.⁴ The second study included 403 patients, most of whom started on spironolactone at 100 mg/d (range, 25-200 mg/d). In addition to facial clearance, patients in this study demonstrated similar rates of partial or complete clearance of acne on the chest (84.0%) and back (80.2%) assessed via a comprehensive acne severity scale.⁵ In both studies, doses of 100 mg/d or higher were most effective, and the median time to initial acne improvement was 3 months, with peak effects occurring after 4 to 6 months of treatment.^4,5 Most patients were using spironolactone monotherapy or spironolactone in combination with topical therapies; however, a minority used it concurrently with oral antibiotics and/or combined oral contraceptives.

Spironolactone has demonstrated comparable efficacy to tetracycline antibiotics. A study comparing the rate of switching to another systemic therapy within 1 year of treatment initiation identified similar rates in patients started on spironolactone (n=962) and those started on tetracyclines (n=4236)(14.4% vs 13.4%, respectively). As switching may indicate treatment failure due to insufficient efficacy, adverse effects, or other causes, these findings may suggest similar effectiveness for spironolactone and tetracyclines.⁶ These treatments also were compared in a randomized controlled trial of 133 patients receiving topical benzoyl peroxide 5% for 6 months and either spironolactone 150 mg/d for 6 months or doxycycline 100 mg/d for 3 months followed by oral placebo for 3 months. At 4 months, spironolactone performed better than doxycycline as assessed using the Adult Female Acne Scoring Tool.³ Although doxycycline was stopped after 3 months and only topical therapy was continued, this finding is notable because guidelines from the American Academy of Dermatology recommend limiting tetracycline use to 3 to 4 months, whereas spironolactone may be continued for prolonged durations.^1,4

While most studies have evaluated the efficacy of spironolactone in adult females, it is increasingly being prescribed in adolescents.⁷ In a study that included 80 females aged 14 to 20 years, 80% (64/80) experienced acne improvement on a median dose of 100 mg/d.⁸ Additionally, in the study evaluating treatment switching rates, more than 80% of 1139 adolescents who were started on spironolactone were not switched to a different systemic therapy within the first year of treatment, demonstrating the efficacy of spironolactone in this demographic.⁶ However, treatment switching was more common among adolescents started on spironolactone compared with those who started on tetracyclines. As noted for adults, the treatment switching rates were the same for spironolactone and tetracycline users; the difference in adolescents may be due to lower influence of hormonal factors or higher therapeutic expectations in this population.⁶

Spironolactone Safety

Spironolactone is well tolerated at doses of 25 to 200 mg/d for acne management. Common adverse effects include diuresis (29% [26/90]), menstrual irregularities (22% [20/90]), fatigue (17% [15/90]), headache (14% [13/90]), and dizziness (12% [11/90]), but they infrequently lead to treatment discontinuation.^4,9 Rates of adverse effects are lower in adolescents compared to adults, although the effects of spironolactone on early endocrine development in adolescents are unknown.⁷ Spironolactone should not be used during pregnancy, and concurrent contraception use is advised because spironolactone has caused feminization of male fetuses in animal studies.^1,10-11

While concerns about potentially severe adverse effects including hypotension, hyperkalemia, and tumorigenicity have been raised, their occurrence in the literature is rare.^5,12-18 In a study evaluating hypotension in 2084 patients taking spironolactone 50 to 200 mg/day for acne, hair loss, and/or hirsutism, 3.1% experienced absolute hypotension, and only 0.26% required dose reduction or discontinuation.¹² Another study of 403 patients taking spironolactone for acne reported a statistically significant but clinically insignificant mean reduction in systolic blood pressure of 3.5 mm Hg.⁵ While clinically relevant hypotension is unlikely to occur, some authors still recommend measuring baseline blood pressure before spironolactone initiation.¹²

Many large studies have demonstrated that hyperkalemia with spironolactone use is rare in young healthy women.^13-15 In one study of patients aged 18 to 45 years treated with spironolactone for acne, only 0.72% of 1802 serum potassium measurements fell within the range of mild hyperkalemia.¹³ Another study found a significantly greater incidence of hyperkalemia in healthy women aged 46 to 65 years compared with women younger than 45 years (16.7% vs <1%; P=.0245).¹⁴ Additionally, among 27 patients taking spironolactone and oral contraceptives containing drospirenone (a spironolactone analog), none had elevated potassium levels.¹⁵ Given these findings, American Academy of Dermatology guidelines suggest that monitoring potassium in young healthy women has low utility but should be considered in those with risk factors including older age; renal and cardiovascular disease; and concurrent medications that interfere with renal, adrenal, and hepatic function.¹ If performed, monitoring should be done within the first few weeks of initiating spironolactone for early detection of hyperkalemia.¹⁶

Spironolactone has a US Food and Drug Administration warning for tumorigenicity based on studies in rats that were given up to 150 times the amount for human therapeutic doses and subsequently developed thyroid, hepatic, testicular, and breast adenomas.¹ However, several large studies in humans have not found an association between spironolactone and breast cancer (BC) development.^1,17,18 Furthermore, a large retrospective study found no increased risk for recurrence in BC survivors treated with spironolactone.² Most carcinogenicity studies include older women, which may limit generalizability of the findings to younger women, who comprise the majority of patients being treated for acne. Recently, however, a retrospective study evaluating healthy females aged 9 to 40 years with acne identified no significant increased risk for BC in patients treated with spironolactone.¹⁷ When compared to tetracyclines, there was a slightly decreased BC risk with spironolactone, providing further support for the latter’s safety. Finally, a large systematic review identified no association between spironolactone and ovarian, bladder, kidney, gastric, or esophageal cancers.¹⁸

Final Thoughts

Over the past several years, an ever-expanding body of literature supporting the efficacy and safety of spironolactone has emerged. While spironolactone has been used off label for decades to treat acne in healthy adult females, there are now strong data to support its efficacy in adolescent females. Notably, spironolactone consistently demonstrates similar effectiveness to first-line tetracycline antibiotics. Additionally, data suggest that spironolactone is safe in patients with a history of BC. Overall, spironolactone is a safe, comparable, and promising alternative to antibiotics for acne management in adult and adolescent females.

Spironolactone is an aldosterone antagonist that first was used as a potassium-sparing diuretic to treat heart failure and hypertension. It also possesses antiandrogenic mechanisms including competitively inhibiting androgen receptors, increasing steroid hormone–binding globulin production, and decreasing 5α-reductase activity.¹ These properties have been leveraged in off-label use for dermatologic conditions including acne, hidradenitis suppurativa, androgenic alopecia, and hirsutism.^1,2 Despite being used off-label to treat acne for more than 40 years, spironolactone has not received US Food and Drug Administration approval for this indication.³ Herein, we review the current evidence for use of spironolactone in acne management.

Spironolactone Efficacy

Spironolactone is efficacious for facial and truncal acne in adult females; it cannot be used in males given its anti-androgenic effects.^4,5 In 2 large studies, spironolactone completely or partially cleared facial acne in 75.5% to 85.1% of patients.^4,5 In the first study, which included 395 patients on a median dose of 100 mg/d (range, 25-200 mg/d), clearance of comedonal, papulopustular, and nodulocystic acne was observed.⁴ The second study included 403 patients, most of whom started on spironolactone at 100 mg/d (range, 25-200 mg/d). In addition to facial clearance, patients in this study demonstrated similar rates of partial or complete clearance of acne on the chest (84.0%) and back (80.2%) assessed via a comprehensive acne severity scale.⁵ In both studies, doses of 100 mg/d or higher were most effective, and the median time to initial acne improvement was 3 months, with peak effects occurring after 4 to 6 months of treatment.^4,5 Most patients were using spironolactone monotherapy or spironolactone in combination with topical therapies; however, a minority used it concurrently with oral antibiotics and/or combined oral contraceptives.

Spironolactone has demonstrated comparable efficacy to tetracycline antibiotics. A study comparing the rate of switching to another systemic therapy within 1 year of treatment initiation identified similar rates in patients started on spironolactone (n=962) and those started on tetracyclines (n=4236)(14.4% vs 13.4%, respectively). As switching may indicate treatment failure due to insufficient efficacy, adverse effects, or other causes, these findings may suggest similar effectiveness for spironolactone and tetracyclines.⁶ These treatments also were compared in a randomized controlled trial of 133 patients receiving topical benzoyl peroxide 5% for 6 months and either spironolactone 150 mg/d for 6 months or doxycycline 100 mg/d for 3 months followed by oral placebo for 3 months. At 4 months, spironolactone performed better than doxycycline as assessed using the Adult Female Acne Scoring Tool.³ Although doxycycline was stopped after 3 months and only topical therapy was continued, this finding is notable because guidelines from the American Academy of Dermatology recommend limiting tetracycline use to 3 to 4 months, whereas spironolactone may be continued for prolonged durations.^1,4

While most studies have evaluated the efficacy of spironolactone in adult females, it is increasingly being prescribed in adolescents.⁷ In a study that included 80 females aged 14 to 20 years, 80% (64/80) experienced acne improvement on a median dose of 100 mg/d.⁸ Additionally, in the study evaluating treatment switching rates, more than 80% of 1139 adolescents who were started on spironolactone were not switched to a different systemic therapy within the first year of treatment, demonstrating the efficacy of spironolactone in this demographic.⁶ However, treatment switching was more common among adolescents started on spironolactone compared with those who started on tetracyclines. As noted for adults, the treatment switching rates were the same for spironolactone and tetracycline users; the difference in adolescents may be due to lower influence of hormonal factors or higher therapeutic expectations in this population.⁶

Spironolactone Safety

Spironolactone is well tolerated at doses of 25 to 200 mg/d for acne management. Common adverse effects include diuresis (29% [26/90]), menstrual irregularities (22% [20/90]), fatigue (17% [15/90]), headache (14% [13/90]), and dizziness (12% [11/90]), but they infrequently lead to treatment discontinuation.^4,9 Rates of adverse effects are lower in adolescents compared to adults, although the effects of spironolactone on early endocrine development in adolescents are unknown.⁷ Spironolactone should not be used during pregnancy, and concurrent contraception use is advised because spironolactone has caused feminization of male fetuses in animal studies.^1,10-11

While concerns about potentially severe adverse effects including hypotension, hyperkalemia, and tumorigenicity have been raised, their occurrence in the literature is rare.^5,12-18 In a study evaluating hypotension in 2084 patients taking spironolactone 50 to 200 mg/day for acne, hair loss, and/or hirsutism, 3.1% experienced absolute hypotension, and only 0.26% required dose reduction or discontinuation.¹² Another study of 403 patients taking spironolactone for acne reported a statistically significant but clinically insignificant mean reduction in systolic blood pressure of 3.5 mm Hg.⁵ While clinically relevant hypotension is unlikely to occur, some authors still recommend measuring baseline blood pressure before spironolactone initiation.¹²

Many large studies have demonstrated that hyperkalemia with spironolactone use is rare in young healthy women.^13-15 In one study of patients aged 18 to 45 years treated with spironolactone for acne, only 0.72% of 1802 serum potassium measurements fell within the range of mild hyperkalemia.¹³ Another study found a significantly greater incidence of hyperkalemia in healthy women aged 46 to 65 years compared with women younger than 45 years (16.7% vs <1%; P=.0245).¹⁴ Additionally, among 27 patients taking spironolactone and oral contraceptives containing drospirenone (a spironolactone analog), none had elevated potassium levels.¹⁵ Given these findings, American Academy of Dermatology guidelines suggest that monitoring potassium in young healthy women has low utility but should be considered in those with risk factors including older age; renal and cardiovascular disease; and concurrent medications that interfere with renal, adrenal, and hepatic function.¹ If performed, monitoring should be done within the first few weeks of initiating spironolactone for early detection of hyperkalemia.¹⁶

Spironolactone has a US Food and Drug Administration warning for tumorigenicity based on studies in rats that were given up to 150 times the amount for human therapeutic doses and subsequently developed thyroid, hepatic, testicular, and breast adenomas.¹ However, several large studies in humans have not found an association between spironolactone and breast cancer (BC) development.^1,17,18 Furthermore, a large retrospective study found no increased risk for recurrence in BC survivors treated with spironolactone.² Most carcinogenicity studies include older women, which may limit generalizability of the findings to younger women, who comprise the majority of patients being treated for acne. Recently, however, a retrospective study evaluating healthy females aged 9 to 40 years with acne identified no significant increased risk for BC in patients treated with spironolactone.¹⁷ When compared to tetracyclines, there was a slightly decreased BC risk with spironolactone, providing further support for the latter’s safety. Finally, a large systematic review identified no association between spironolactone and ovarian, bladder, kidney, gastric, or esophageal cancers.¹⁸

Final Thoughts

Over the past several years, an ever-expanding body of literature supporting the efficacy and safety of spironolactone has emerged. While spironolactone has been used off label for decades to treat acne in healthy adult females, there are now strong data to support its efficacy in adolescent females. Notably, spironolactone consistently demonstrates similar effectiveness to first-line tetracycline antibiotics. Additionally, data suggest that spironolactone is safe in patients with a history of BC. Overall, spironolactone is a safe, comparable, and promising alternative to antibiotics for acne management in adult and adolescent females.

Spironolactone is an aldosterone antagonist that first was used as a potassium-sparing diuretic to treat heart failure and hypertension. It also possesses antiandrogenic mechanisms including competitively inhibiting androgen receptors, increasing steroid hormone–binding globulin production, and decreasing 5α-reductase activity.¹ These properties have been leveraged in off-label use for dermatologic conditions including acne, hidradenitis suppurativa, androgenic alopecia, and hirsutism.^1,2 Despite being used off-label to treat acne for more than 40 years, spironolactone has not received US Food and Drug Administration approval for this indication.³ Herein, we review the current evidence for use of spironolactone in acne management.

Spironolactone Efficacy

Spironolactone is efficacious for facial and truncal acne in adult females; it cannot be used in males given its anti-androgenic effects.^4,5 In 2 large studies, spironolactone completely or partially cleared facial acne in 75.5% to 85.1% of patients.^4,5 In the first study, which included 395 patients on a median dose of 100 mg/d (range, 25-200 mg/d), clearance of comedonal, papulopustular, and nodulocystic acne was observed.⁴ The second study included 403 patients, most of whom started on spironolactone at 100 mg/d (range, 25-200 mg/d). In addition to facial clearance, patients in this study demonstrated similar rates of partial or complete clearance of acne on the chest (84.0%) and back (80.2%) assessed via a comprehensive acne severity scale.⁵ In both studies, doses of 100 mg/d or higher were most effective, and the median time to initial acne improvement was 3 months, with peak effects occurring after 4 to 6 months of treatment.^4,5 Most patients were using spironolactone monotherapy or spironolactone in combination with topical therapies; however, a minority used it concurrently with oral antibiotics and/or combined oral contraceptives.

Spironolactone has demonstrated comparable efficacy to tetracycline antibiotics. A study comparing the rate of switching to another systemic therapy within 1 year of treatment initiation identified similar rates in patients started on spironolactone (n=962) and those started on tetracyclines (n=4236)(14.4% vs 13.4%, respectively). As switching may indicate treatment failure due to insufficient efficacy, adverse effects, or other causes, these findings may suggest similar effectiveness for spironolactone and tetracyclines.⁶ These treatments also were compared in a randomized controlled trial of 133 patients receiving topical benzoyl peroxide 5% for 6 months and either spironolactone 150 mg/d for 6 months or doxycycline 100 mg/d for 3 months followed by oral placebo for 3 months. At 4 months, spironolactone performed better than doxycycline as assessed using the Adult Female Acne Scoring Tool.³ Although doxycycline was stopped after 3 months and only topical therapy was continued, this finding is notable because guidelines from the American Academy of Dermatology recommend limiting tetracycline use to 3 to 4 months, whereas spironolactone may be continued for prolonged durations.^1,4

While most studies have evaluated the efficacy of spironolactone in adult females, it is increasingly being prescribed in adolescents.⁷ In a study that included 80 females aged 14 to 20 years, 80% (64/80) experienced acne improvement on a median dose of 100 mg/d.⁸ Additionally, in the study evaluating treatment switching rates, more than 80% of 1139 adolescents who were started on spironolactone were not switched to a different systemic therapy within the first year of treatment, demonstrating the efficacy of spironolactone in this demographic.⁶ However, treatment switching was more common among adolescents started on spironolactone compared with those who started on tetracyclines. As noted for adults, the treatment switching rates were the same for spironolactone and tetracycline users; the difference in adolescents may be due to lower influence of hormonal factors or higher therapeutic expectations in this population.⁶

Spironolactone Safety

Spironolactone is well tolerated at doses of 25 to 200 mg/d for acne management. Common adverse effects include diuresis (29% [26/90]), menstrual irregularities (22% [20/90]), fatigue (17% [15/90]), headache (14% [13/90]), and dizziness (12% [11/90]), but they infrequently lead to treatment discontinuation.^4,9 Rates of adverse effects are lower in adolescents compared to adults, although the effects of spironolactone on early endocrine development in adolescents are unknown.⁷ Spironolactone should not be used during pregnancy, and concurrent contraception use is advised because spironolactone has caused feminization of male fetuses in animal studies.^1,10-11

While concerns about potentially severe adverse effects including hypotension, hyperkalemia, and tumorigenicity have been raised, their occurrence in the literature is rare.^5,12-18 In a study evaluating hypotension in 2084 patients taking spironolactone 50 to 200 mg/day for acne, hair loss, and/or hirsutism, 3.1% experienced absolute hypotension, and only 0.26% required dose reduction or discontinuation.¹² Another study of 403 patients taking spironolactone for acne reported a statistically significant but clinically insignificant mean reduction in systolic blood pressure of 3.5 mm Hg.⁵ While clinically relevant hypotension is unlikely to occur, some authors still recommend measuring baseline blood pressure before spironolactone initiation.¹²

Many large studies have demonstrated that hyperkalemia with spironolactone use is rare in young healthy women.^13-15 In one study of patients aged 18 to 45 years treated with spironolactone for acne, only 0.72% of 1802 serum potassium measurements fell within the range of mild hyperkalemia.¹³ Another study found a significantly greater incidence of hyperkalemia in healthy women aged 46 to 65 years compared with women younger than 45 years (16.7% vs <1%; P=.0245).¹⁴ Additionally, among 27 patients taking spironolactone and oral contraceptives containing drospirenone (a spironolactone analog), none had elevated potassium levels.¹⁵ Given these findings, American Academy of Dermatology guidelines suggest that monitoring potassium in young healthy women has low utility but should be considered in those with risk factors including older age; renal and cardiovascular disease; and concurrent medications that interfere with renal, adrenal, and hepatic function.¹ If performed, monitoring should be done within the first few weeks of initiating spironolactone for early detection of hyperkalemia.¹⁶

Spironolactone has a US Food and Drug Administration warning for tumorigenicity based on studies in rats that were given up to 150 times the amount for human therapeutic doses and subsequently developed thyroid, hepatic, testicular, and breast adenomas.¹ However, several large studies in humans have not found an association between spironolactone and breast cancer (BC) development.^1,17,18 Furthermore, a large retrospective study found no increased risk for recurrence in BC survivors treated with spironolactone.² Most carcinogenicity studies include older women, which may limit generalizability of the findings to younger women, who comprise the majority of patients being treated for acne. Recently, however, a retrospective study evaluating healthy females aged 9 to 40 years with acne identified no significant increased risk for BC in patients treated with spironolactone.¹⁷ When compared to tetracyclines, there was a slightly decreased BC risk with spironolactone, providing further support for the latter’s safety. Finally, a large systematic review identified no association between spironolactone and ovarian, bladder, kidney, gastric, or esophageal cancers.¹⁸

Final Thoughts

Over the past several years, an ever-expanding body of literature supporting the efficacy and safety of spironolactone has emerged. While spironolactone has been used off label for decades to treat acne in healthy adult females, there are now strong data to support its efficacy in adolescent females. Notably, spironolactone consistently demonstrates similar effectiveness to first-line tetracycline antibiotics. Additionally, data suggest that spironolactone is safe in patients with a history of BC. Overall, spironolactone is a safe, comparable, and promising alternative to antibiotics for acne management in adult and adolescent females.

THE DIAGNOSIS: Cutaneous Cryptococcosis

Biopsy of the ulcerated nodule showed numerous yeastlike organisms within clear mucinous capsules and with some surrounding inflammation. On Grocott methenamine silver staining, the organisms stained black. Workup for disseminated cryptococcus was negative, leading to a diagnosis of primary cutaneous cryptococcosis in the setting of immunosuppression. Notably, cryptococcosis infection has been reported in patients taking fingolimod (a sphingosine-1-phosphate receptor) for multiple sclerosis, which was the case for our patient.¹

The genus Cryptococcus comprises more than 30 species of encapsulated basidiomycetous fungi distributed ubiquitously in nature. Currently, only 2 species are known to cause infectious disease in humans: Cryptococcus neoformans, which affects both immunocompromised and immunocompetent patients and frequently is isolated from pigeon droppings, as well as Cryptococcus gatti, which primarily affects immunocompetent patients and is more commonly isolated from soil and decaying wood.²

Primary cutaneous cryptococcosis (PCC), characterized by direct inoculation of C neoformans or C gatti via skin injury, is rare and typically is seen in patients with decreased cell-mediated immunity, such as those on chronic corticosteroid therapy, solid-organ transplant recipients, and those with HIV.³ Primary cutaneous cryptococcosis typically manifests as a solitary or confined lesion on exposed areas of the skin and often is accompanied by regional lymphadenopathy.^4,5 The most common cutaneous findings associated with PCC include ulceration, cellulitis, and whitlow.⁵ In immunocompetent hosts, frequently affected sites include the arms, fingers, and face, while the trunk and lower extremities are more commonly affected in immunocompromised hosts.³ Secondary cutaneous cryptococcosis occurs through hematologic spread in patients with disseminated cryptococcosis after inhalation of Cryptococcosis spores and differs from PCC in that it typically manifests as multiple lesions scattered on both exposed and covered areas of the skin. Patients also may have signs and symptoms of disseminated cryptococcosis such as pneumonia and/or meningitis at presentation.⁵

Despite the difference between PCC and secondary cutaneous cryptococcosis, almost every type of skin lesion has been observed in cryptococcosis, including pustules, nodules, vesicles, acneform lesions, purpura, ulcers, abscesses, molluscumlike lesions, granulomas, draining sinuses, and cellulitis.^6,7

Cutaneous cryptococcosis generally is associated with 2 types of histologic reactions: gelatinous and granulomatous. The gelatinous reaction shows numerous yeastlike organisms ranging from 4 μm to 12 μm in diameter with large mucinous polysaccharide capsules and scant inflammation. Organisms may be seen in mucoid sheets.⁸ The granulomatous type shows a more pronounced reaction with fewer organisms ranging from 2 μm to 4 μm in diameter found within giant cells, histiocytes, and lymphocytes.^6,9 Areas of necrosis occasionally can be observed.⁸

It is important to consider infection with Blastomyces dermatitidis and Histoplasma capsulatum in the differential Both entities can manifest as necrotizing granulomas on histology (Figures 1 and 2).¹⁰ Microscopic morphology can help differentiate these pathogenic fungi from Cryptococcus diagnosis of cryptococcosis. species which show pleomorphic, narrow-based budding yeast with wide capsules. In contrast, H capsulatum is characterized by small, intracellular, yeastlike cells with microconidia and macroconidia, while B dermatitidis is distinguished by spherical, thick-walled cells with broad-based budding.¹¹ Capsular material also can help distinguish Cryptococcus from other pathogenic fungi. Special stains highlighting the polysaccharide capsule of Cryptococcus can best identify the yeast. The capsule stains red with periodic acid–Schiff, blue with Alcian blue, and black with Grocott methenamine silver. Mucicarmine is especially useful as it can stain the mucinous capsule pinkish red and typically does not stain other pathogenic fungi.¹² Capsule-deficient organisms can lead to considerable difficulties in diagnosis given the organisms can vary in size and may mimic H capsulatum or B dermatitidis. The Fontana-Masson stain is a valuable tool in identifying capsule-deficient organisms, as melanin is found in Cryptococcus cell walls; thus, positive staining excludes H capsulatum and B dermatitidis.¹³

Cutaneous foreign body granuloma, which refers to a granulomatous inflammatory reaction to a foreign body in the skin, is another differential diagnosis that is important to distinguish from cutaneous cryptococcosis. On histology, a collection of histiocytes surround the inert material, forming giant cells without an immune response (Figure 3).¹⁰ In contrast, granulomas caused by infectious etiologies (eg, Cryptococcus species) have an associated adaptive immune response and can be further classified as necrotizing or non-necrotizing. Necrotizing granulomas have a distinct central necrosis with a surrounding lymphohistiocytic reaction with peripheral chronic inflammation.¹⁰

Sweet syndrome is another mimicker of cutaneous cryptococcosis. A histologic variant of Sweet syndrome has been reported that has characteristic cutaneous lesions clinically but shows basophilic bodies with a surrounding halo on pathology that can be mistaken for Cryptococcus yeast. Classic histopathology of Sweet syndrome features papillary dermal edema with neutrophil or histiocytelike inflammatory infiltrate (Figure 4). Identification of Sweet syndrome can be aided by positive myeloperoxidase staining and negative periodic acid–Schiff staining.^14,15

THE DIAGNOSIS: Cutaneous Cryptococcosis

Biopsy of the ulcerated nodule showed numerous yeastlike organisms within clear mucinous capsules and with some surrounding inflammation. On Grocott methenamine silver staining, the organisms stained black. Workup for disseminated cryptococcus was negative, leading to a diagnosis of primary cutaneous cryptococcosis in the setting of immunosuppression. Notably, cryptococcosis infection has been reported in patients taking fingolimod (a sphingosine-1-phosphate receptor) for multiple sclerosis, which was the case for our patient.¹

The genus Cryptococcus comprises more than 30 species of encapsulated basidiomycetous fungi distributed ubiquitously in nature. Currently, only 2 species are known to cause infectious disease in humans: Cryptococcus neoformans, which affects both immunocompromised and immunocompetent patients and frequently is isolated from pigeon droppings, as well as Cryptococcus gatti, which primarily affects immunocompetent patients and is more commonly isolated from soil and decaying wood.²

Primary cutaneous cryptococcosis (PCC), characterized by direct inoculation of C neoformans or C gatti via skin injury, is rare and typically is seen in patients with decreased cell-mediated immunity, such as those on chronic corticosteroid therapy, solid-organ transplant recipients, and those with HIV.³ Primary cutaneous cryptococcosis typically manifests as a solitary or confined lesion on exposed areas of the skin and often is accompanied by regional lymphadenopathy.^4,5 The most common cutaneous findings associated with PCC include ulceration, cellulitis, and whitlow.⁵ In immunocompetent hosts, frequently affected sites include the arms, fingers, and face, while the trunk and lower extremities are more commonly affected in immunocompromised hosts.³ Secondary cutaneous cryptococcosis occurs through hematologic spread in patients with disseminated cryptococcosis after inhalation of Cryptococcosis spores and differs from PCC in that it typically manifests as multiple lesions scattered on both exposed and covered areas of the skin. Patients also may have signs and symptoms of disseminated cryptococcosis such as pneumonia and/or meningitis at presentation.⁵

Despite the difference between PCC and secondary cutaneous cryptococcosis, almost every type of skin lesion has been observed in cryptococcosis, including pustules, nodules, vesicles, acneform lesions, purpura, ulcers, abscesses, molluscumlike lesions, granulomas, draining sinuses, and cellulitis.^6,7

Cutaneous cryptococcosis generally is associated with 2 types of histologic reactions: gelatinous and granulomatous. The gelatinous reaction shows numerous yeastlike organisms ranging from 4 μm to 12 μm in diameter with large mucinous polysaccharide capsules and scant inflammation. Organisms may be seen in mucoid sheets.⁸ The granulomatous type shows a more pronounced reaction with fewer organisms ranging from 2 μm to 4 μm in diameter found within giant cells, histiocytes, and lymphocytes.^6,9 Areas of necrosis occasionally can be observed.⁸

It is important to consider infection with Blastomyces dermatitidis and Histoplasma capsulatum in the differential Both entities can manifest as necrotizing granulomas on histology (Figures 1 and 2).¹⁰ Microscopic morphology can help differentiate these pathogenic fungi from Cryptococcus diagnosis of cryptococcosis. species which show pleomorphic, narrow-based budding yeast with wide capsules. In contrast, H capsulatum is characterized by small, intracellular, yeastlike cells with microconidia and macroconidia, while B dermatitidis is distinguished by spherical, thick-walled cells with broad-based budding.¹¹ Capsular material also can help distinguish Cryptococcus from other pathogenic fungi. Special stains highlighting the polysaccharide capsule of Cryptococcus can best identify the yeast. The capsule stains red with periodic acid–Schiff, blue with Alcian blue, and black with Grocott methenamine silver. Mucicarmine is especially useful as it can stain the mucinous capsule pinkish red and typically does not stain other pathogenic fungi.¹² Capsule-deficient organisms can lead to considerable difficulties in diagnosis given the organisms can vary in size and may mimic H capsulatum or B dermatitidis. The Fontana-Masson stain is a valuable tool in identifying capsule-deficient organisms, as melanin is found in Cryptococcus cell walls; thus, positive staining excludes H capsulatum and B dermatitidis.¹³

Cutaneous foreign body granuloma, which refers to a granulomatous inflammatory reaction to a foreign body in the skin, is another differential diagnosis that is important to distinguish from cutaneous cryptococcosis. On histology, a collection of histiocytes surround the inert material, forming giant cells without an immune response (Figure 3).¹⁰ In contrast, granulomas caused by infectious etiologies (eg, Cryptococcus species) have an associated adaptive immune response and can be further classified as necrotizing or non-necrotizing. Necrotizing granulomas have a distinct central necrosis with a surrounding lymphohistiocytic reaction with peripheral chronic inflammation.¹⁰

Sweet syndrome is another mimicker of cutaneous cryptococcosis. A histologic variant of Sweet syndrome has been reported that has characteristic cutaneous lesions clinically but shows basophilic bodies with a surrounding halo on pathology that can be mistaken for Cryptococcus yeast. Classic histopathology of Sweet syndrome features papillary dermal edema with neutrophil or histiocytelike inflammatory infiltrate (Figure 4). Identification of Sweet syndrome can be aided by positive myeloperoxidase staining and negative periodic acid–Schiff staining.^14,15

THE DIAGNOSIS: Cutaneous Cryptococcosis

Biopsy of the ulcerated nodule showed numerous yeastlike organisms within clear mucinous capsules and with some surrounding inflammation. On Grocott methenamine silver staining, the organisms stained black. Workup for disseminated cryptococcus was negative, leading to a diagnosis of primary cutaneous cryptococcosis in the setting of immunosuppression. Notably, cryptococcosis infection has been reported in patients taking fingolimod (a sphingosine-1-phosphate receptor) for multiple sclerosis, which was the case for our patient.¹

The genus Cryptococcus comprises more than 30 species of encapsulated basidiomycetous fungi distributed ubiquitously in nature. Currently, only 2 species are known to cause infectious disease in humans: Cryptococcus neoformans, which affects both immunocompromised and immunocompetent patients and frequently is isolated from pigeon droppings, as well as Cryptococcus gatti, which primarily affects immunocompetent patients and is more commonly isolated from soil and decaying wood.²

Primary cutaneous cryptococcosis (PCC), characterized by direct inoculation of C neoformans or C gatti via skin injury, is rare and typically is seen in patients with decreased cell-mediated immunity, such as those on chronic corticosteroid therapy, solid-organ transplant recipients, and those with HIV.³ Primary cutaneous cryptococcosis typically manifests as a solitary or confined lesion on exposed areas of the skin and often is accompanied by regional lymphadenopathy.^4,5 The most common cutaneous findings associated with PCC include ulceration, cellulitis, and whitlow.⁵ In immunocompetent hosts, frequently affected sites include the arms, fingers, and face, while the trunk and lower extremities are more commonly affected in immunocompromised hosts.³ Secondary cutaneous cryptococcosis occurs through hematologic spread in patients with disseminated cryptococcosis after inhalation of Cryptococcosis spores and differs from PCC in that it typically manifests as multiple lesions scattered on both exposed and covered areas of the skin. Patients also may have signs and symptoms of disseminated cryptococcosis such as pneumonia and/or meningitis at presentation.⁵

Despite the difference between PCC and secondary cutaneous cryptococcosis, almost every type of skin lesion has been observed in cryptococcosis, including pustules, nodules, vesicles, acneform lesions, purpura, ulcers, abscesses, molluscumlike lesions, granulomas, draining sinuses, and cellulitis.^6,7

Cutaneous cryptococcosis generally is associated with 2 types of histologic reactions: gelatinous and granulomatous. The gelatinous reaction shows numerous yeastlike organisms ranging from 4 μm to 12 μm in diameter with large mucinous polysaccharide capsules and scant inflammation. Organisms may be seen in mucoid sheets.⁸ The granulomatous type shows a more pronounced reaction with fewer organisms ranging from 2 μm to 4 μm in diameter found within giant cells, histiocytes, and lymphocytes.^6,9 Areas of necrosis occasionally can be observed.⁸

It is important to consider infection with Blastomyces dermatitidis and Histoplasma capsulatum in the differential Both entities can manifest as necrotizing granulomas on histology (Figures 1 and 2).¹⁰ Microscopic morphology can help differentiate these pathogenic fungi from Cryptococcus diagnosis of cryptococcosis. species which show pleomorphic, narrow-based budding yeast with wide capsules. In contrast, H capsulatum is characterized by small, intracellular, yeastlike cells with microconidia and macroconidia, while B dermatitidis is distinguished by spherical, thick-walled cells with broad-based budding.¹¹ Capsular material also can help distinguish Cryptococcus from other pathogenic fungi. Special stains highlighting the polysaccharide capsule of Cryptococcus can best identify the yeast. The capsule stains red with periodic acid–Schiff, blue with Alcian blue, and black with Grocott methenamine silver. Mucicarmine is especially useful as it can stain the mucinous capsule pinkish red and typically does not stain other pathogenic fungi.¹² Capsule-deficient organisms can lead to considerable difficulties in diagnosis given the organisms can vary in size and may mimic H capsulatum or B dermatitidis. The Fontana-Masson stain is a valuable tool in identifying capsule-deficient organisms, as melanin is found in Cryptococcus cell walls; thus, positive staining excludes H capsulatum and B dermatitidis.¹³

Cutaneous foreign body granuloma, which refers to a granulomatous inflammatory reaction to a foreign body in the skin, is another differential diagnosis that is important to distinguish from cutaneous cryptococcosis. On histology, a collection of histiocytes surround the inert material, forming giant cells without an immune response (Figure 3).¹⁰ In contrast, granulomas caused by infectious etiologies (eg, Cryptococcus species) have an associated adaptive immune response and can be further classified as necrotizing or non-necrotizing. Necrotizing granulomas have a distinct central necrosis with a surrounding lymphohistiocytic reaction with peripheral chronic inflammation.¹⁰

Sweet syndrome is another mimicker of cutaneous cryptococcosis. A histologic variant of Sweet syndrome has been reported that has characteristic cutaneous lesions clinically but shows basophilic bodies with a surrounding halo on pathology that can be mistaken for Cryptococcus yeast. Classic histopathology of Sweet syndrome features papillary dermal edema with neutrophil or histiocytelike inflammatory infiltrate (Figure 4). Identification of Sweet syndrome can be aided by positive myeloperoxidase staining and negative periodic acid–Schiff staining.^14,15