Cutis

Academic promotion requires evidence of scholastic production. The number of publications by a scientist is the most frequently reported metric of scholastic production, but it does not account for the impact of publications. The h-index is a bibliometric measure that combines both volume and impact of scientific contributions. The physicist Jorge E. Hirsch introduced this metric in 2005.¹ He defined it as the number of publications (h) by an author that have been cited at least h times. For example, a scientist with 30 publications including 12 that have been cited at least 12 times each has an h-index of 12. h-Index is a superior predictor of future scientific achievement in physics compared with total citation count, total publication count, and citations per publication. Hirsch² proposed h-index thresholds of 12 and 18 for advancement to associate professor and full professor in physics, respectively.²

h-Index values are not comparable across academic disciplines because they are influenced by the number of journals and authors within the field. Scientists in disciplines with numerous scholars and publications will have higher h-indices. For example, the mean h-index for full professors of cardiothoracic anesthesiology is 12, but the mean h-index for full professors of urology is 22.^3,4 Hence, h-index thresholds for professional advancement cannot be generalized but must be calculated on a granular, specialty-specific basis.

In a prior study on h-index among academic dermatologists in the United States, John et al⁵ reported that fellowship-trained dermatologists had a significantly higher mean h-index than those without fellowship training (13.2 vs 11.7; P<.001). They further found the mean h-index increased with academic rank.⁵

In our study, we measured mean and median h-indices among associate and full professors of dermatology in academic training programs in the United States with the goal of describing h-index distributions in these 2 academic ranks. We further sought to measure regional differences in h-index between northeastern, southern, central, and western states as defined by the National Resident Matching Program.

Methods

Institutional review board approval was deferred because the study did not require patient information or participation. Using the Association of American Medical Colleges Electronic Residency Application Service website (https://www.aamc.org/services/eras/) we identified dermatology residency training programs accredited by the Accreditation Council for Graduate Medical Education and participating in the Electronic Residency Application Service for the National Resident Matching Program in the United States. We visited the official website of each residency program and identified all associate and full professors of dermatology for further study. We included all faculty members listed as professor, clinical professor, associate professor, or clinical associate professor, and excluded assistant professor, volunteer faculty, research professor, and research associate professor. All faculty held an MD degree or an equivalent degree, such as MBBS or MDCM.

We used the Thomson Reuters (now Clarivate Analytics) Web of Science to calculate h-index and publication counts. The initial search was basic using the professor’s last name and first initial. We then augmented this list by searching for all variations of each professor’s name, with or without middle initial. Each publication in the search results was confirmed as belonging to the author of interest by verifying coauthors, institution information, and subject material. For authors with common names, we additionally consulted their online university profiles for specific names used in their “Selected Publications” lists. In a minority of cases, we also limited Research Domain to “dermatology.” Referring to the verified publication list for each dermatology professor, we used the Web of Science Citation Report function to determine number of publications and h-index for the individual. We tabulated results for associate and full professors and subgrouped those results into 4 geographic regions—northeastern, southern, central, and western states—according to the map used by the National Resident Matching Program. Descriptive statistics were performed with Microsoft Excel.

Results

We identified 300 associate professors and 352 full professors from 81 academic institutions. The number of associate professors per institution ranged from 1 to 25; the number of full professors per institution ranged from 1 to 16. The median and mean h-indices for associate and full professors, including interquartile values, are shown in the Table. There was a broad range of h-index scores among both academic ranks; median and mean h-indices varied more than 5-fold between the bottom and upper quartiles in both associate and full professor cohorts. Median interquartile h-index values for upper-quartile associate professors overlapped with those of lower-quartile full professors (Figure 1). h-Index for associate and full professors was similar across the 4 regions defined by the National Resident Matching Program. Median h-index was highest for full professors in western states and lowest for associate professors in southern states (Figure 2).

Comment

Professional advancement in academic medicine requires scholastic production. The h-index, defined as the number of publications (h) that have been cited at least h times, is a bibliometric measure that accounts for both volume and impact of an individual’s scientific productivity. The h-index would be a useful tool for determining professional advancement in academic dermatology departments. In this project, we calculated h-index values for 300 associate professors and 352 full professors of dermatology in the United States. We found the median h-index for associate professors was 8 and the median h-index for full professors was 21. There was more than a 5-fold variation in median and mean h-indices between lower and upper quartiles within both the associate and full professor cohorts. The highest median and mean h-indices were found among full professors of dermatology in western states. These results provide the opportunity for academic dermatologists and institutions to compare their research contributions with peers across the United States.

Our results support those of John et al⁵ who also found academic rank in dermatology was correlated with h-index. Scopus, Web of Science, and Google Scholar can be used to calculate h-index, but they may return different scores for the same individual.⁶ John et al⁵ used the Scopus database to calculate h-index. We used Web of Science because Scopus only includes citations since 1996 and Web of Science was used in the original h-index studies by Hirsch.^1,2 Institutions that adopt h-index criteria for advancement and resource distribution decisions should be aware that database selection can affect h-index scores.

Caveats With the h-Index
Flaws in the h-index include inflationary effects of self-citation, time bias, and excessive coauthorship. Individuals can increase their h-index by routinely citing their own publications. However, Engqvist and Frommen⁷ found tripling self-citations increased the h-index by only 1.

Citations tend to increase with time, and authors who have been active for longer periods will have a higher h-index. It is more difficult for junior faculty to distinguish themselves with the h-index, as it takes time for even the most impactful publications to gain citations. Major scientific papers can take years from conception to publication, and an outstanding paper that is 1 year old would have fewer citations than an equally impactful paper that is 10 years old. To adjust for the effect of time bias, Hirsch² proposed the m-index, in which the h-index is divided by the years between the author’s first and last publication. He proposed that an m-index of 1 would indicate a successful scientist, 2 an outstanding scientist, and 3 a unique individual.²

The literature is increasingly dominated by teams of coauthors, and the number of coauthors within each team has increased over the last 5 decades.⁸ h-Indices will increase if this trend continues, making it difficult to compare h-indices between different eras. Prosperi et al⁹ found national differences in kinship-based coauthorship, suggesting nepotism may influence decisions in assigning authorship status. h-Index valuations do not require evidence of meaningful contribution to the work but simply rely on contributors’ self-governance in assigning authorship status.

The h-index also has a bias against highly cited papers. A scientist with a small number of highly influential papers may have a smaller h-index than a scientist with more papers of modest impact. Finally, an author who has changed names (eg, due to marriage) may have an artificially low h-index, as a standard database search would miss publications under a maiden name.

Limitations
This study is limited by possible operator error when compiling each author’s publication list through Web of Science. Our search and refinement methodology took into account that authors may publish with slight variations in name, in various subject areas and fields, and with different institutions and coauthors. Each publication populated through Web of Science was carefully verified by the principal investigator; however, overestimation or underestimation of the number of publications and citations was possible, as the publication lists were not verified by the studied associate and full professors themselves. Our results are consistent with the h-index bar charts published by John et al⁵ using an alternate citation index, Scopus, which tends to corroborate our findings. This study also is limited by possible time bias because we did not correct the h-index for years of active publication (m-index).

Conclusion

In summary, we found the median h-index for associate professors was 8 and the median h-index for full professors was 21. We found a broad range of h-index values within each academic rank. h-Index for upper-quartile associate professors overlapped with those of lower-quartile full professors. Our results suggest professional advancement occurs over a broad range of scholastic production. Adopting requirements for minimum h-index thresholds for application for promotion might reduce disparities between rank and scientific contributions. We encourage use of the h-index for tracking academic progression and as a parameter to consider in academic promotion.

Academic promotion requires evidence of scholastic production. The number of publications by a scientist is the most frequently reported metric of scholastic production, but it does not account for the impact of publications. The h-index is a bibliometric measure that combines both volume and impact of scientific contributions. The physicist Jorge E. Hirsch introduced this metric in 2005.¹ He defined it as the number of publications (h) by an author that have been cited at least h times. For example, a scientist with 30 publications including 12 that have been cited at least 12 times each has an h-index of 12. h-Index is a superior predictor of future scientific achievement in physics compared with total citation count, total publication count, and citations per publication. Hirsch² proposed h-index thresholds of 12 and 18 for advancement to associate professor and full professor in physics, respectively.²

h-Index values are not comparable across academic disciplines because they are influenced by the number of journals and authors within the field. Scientists in disciplines with numerous scholars and publications will have higher h-indices. For example, the mean h-index for full professors of cardiothoracic anesthesiology is 12, but the mean h-index for full professors of urology is 22.^3,4 Hence, h-index thresholds for professional advancement cannot be generalized but must be calculated on a granular, specialty-specific basis.

In a prior study on h-index among academic dermatologists in the United States, John et al⁵ reported that fellowship-trained dermatologists had a significantly higher mean h-index than those without fellowship training (13.2 vs 11.7; P<.001). They further found the mean h-index increased with academic rank.⁵

In our study, we measured mean and median h-indices among associate and full professors of dermatology in academic training programs in the United States with the goal of describing h-index distributions in these 2 academic ranks. We further sought to measure regional differences in h-index between northeastern, southern, central, and western states as defined by the National Resident Matching Program.

Methods

Institutional review board approval was deferred because the study did not require patient information or participation. Using the Association of American Medical Colleges Electronic Residency Application Service website (https://www.aamc.org/services/eras/) we identified dermatology residency training programs accredited by the Accreditation Council for Graduate Medical Education and participating in the Electronic Residency Application Service for the National Resident Matching Program in the United States. We visited the official website of each residency program and identified all associate and full professors of dermatology for further study. We included all faculty members listed as professor, clinical professor, associate professor, or clinical associate professor, and excluded assistant professor, volunteer faculty, research professor, and research associate professor. All faculty held an MD degree or an equivalent degree, such as MBBS or MDCM.

We used the Thomson Reuters (now Clarivate Analytics) Web of Science to calculate h-index and publication counts. The initial search was basic using the professor’s last name and first initial. We then augmented this list by searching for all variations of each professor’s name, with or without middle initial. Each publication in the search results was confirmed as belonging to the author of interest by verifying coauthors, institution information, and subject material. For authors with common names, we additionally consulted their online university profiles for specific names used in their “Selected Publications” lists. In a minority of cases, we also limited Research Domain to “dermatology.” Referring to the verified publication list for each dermatology professor, we used the Web of Science Citation Report function to determine number of publications and h-index for the individual. We tabulated results for associate and full professors and subgrouped those results into 4 geographic regions—northeastern, southern, central, and western states—according to the map used by the National Resident Matching Program. Descriptive statistics were performed with Microsoft Excel.

Results

We identified 300 associate professors and 352 full professors from 81 academic institutions. The number of associate professors per institution ranged from 1 to 25; the number of full professors per institution ranged from 1 to 16. The median and mean h-indices for associate and full professors, including interquartile values, are shown in the Table. There was a broad range of h-index scores among both academic ranks; median and mean h-indices varied more than 5-fold between the bottom and upper quartiles in both associate and full professor cohorts. Median interquartile h-index values for upper-quartile associate professors overlapped with those of lower-quartile full professors (Figure 1). h-Index for associate and full professors was similar across the 4 regions defined by the National Resident Matching Program. Median h-index was highest for full professors in western states and lowest for associate professors in southern states (Figure 2).

Comment

Professional advancement in academic medicine requires scholastic production. The h-index, defined as the number of publications (h) that have been cited at least h times, is a bibliometric measure that accounts for both volume and impact of an individual’s scientific productivity. The h-index would be a useful tool for determining professional advancement in academic dermatology departments. In this project, we calculated h-index values for 300 associate professors and 352 full professors of dermatology in the United States. We found the median h-index for associate professors was 8 and the median h-index for full professors was 21. There was more than a 5-fold variation in median and mean h-indices between lower and upper quartiles within both the associate and full professor cohorts. The highest median and mean h-indices were found among full professors of dermatology in western states. These results provide the opportunity for academic dermatologists and institutions to compare their research contributions with peers across the United States.

Our results support those of John et al⁵ who also found academic rank in dermatology was correlated with h-index. Scopus, Web of Science, and Google Scholar can be used to calculate h-index, but they may return different scores for the same individual.⁶ John et al⁵ used the Scopus database to calculate h-index. We used Web of Science because Scopus only includes citations since 1996 and Web of Science was used in the original h-index studies by Hirsch.^1,2 Institutions that adopt h-index criteria for advancement and resource distribution decisions should be aware that database selection can affect h-index scores.

Caveats With the h-Index
Flaws in the h-index include inflationary effects of self-citation, time bias, and excessive coauthorship. Individuals can increase their h-index by routinely citing their own publications. However, Engqvist and Frommen⁷ found tripling self-citations increased the h-index by only 1.

Citations tend to increase with time, and authors who have been active for longer periods will have a higher h-index. It is more difficult for junior faculty to distinguish themselves with the h-index, as it takes time for even the most impactful publications to gain citations. Major scientific papers can take years from conception to publication, and an outstanding paper that is 1 year old would have fewer citations than an equally impactful paper that is 10 years old. To adjust for the effect of time bias, Hirsch² proposed the m-index, in which the h-index is divided by the years between the author’s first and last publication. He proposed that an m-index of 1 would indicate a successful scientist, 2 an outstanding scientist, and 3 a unique individual.²

The literature is increasingly dominated by teams of coauthors, and the number of coauthors within each team has increased over the last 5 decades.⁸ h-Indices will increase if this trend continues, making it difficult to compare h-indices between different eras. Prosperi et al⁹ found national differences in kinship-based coauthorship, suggesting nepotism may influence decisions in assigning authorship status. h-Index valuations do not require evidence of meaningful contribution to the work but simply rely on contributors’ self-governance in assigning authorship status.

The h-index also has a bias against highly cited papers. A scientist with a small number of highly influential papers may have a smaller h-index than a scientist with more papers of modest impact. Finally, an author who has changed names (eg, due to marriage) may have an artificially low h-index, as a standard database search would miss publications under a maiden name.

Limitations
This study is limited by possible operator error when compiling each author’s publication list through Web of Science. Our search and refinement methodology took into account that authors may publish with slight variations in name, in various subject areas and fields, and with different institutions and coauthors. Each publication populated through Web of Science was carefully verified by the principal investigator; however, overestimation or underestimation of the number of publications and citations was possible, as the publication lists were not verified by the studied associate and full professors themselves. Our results are consistent with the h-index bar charts published by John et al⁵ using an alternate citation index, Scopus, which tends to corroborate our findings. This study also is limited by possible time bias because we did not correct the h-index for years of active publication (m-index).

Conclusion

In summary, we found the median h-index for associate professors was 8 and the median h-index for full professors was 21. We found a broad range of h-index values within each academic rank. h-Index for upper-quartile associate professors overlapped with those of lower-quartile full professors. Our results suggest professional advancement occurs over a broad range of scholastic production. Adopting requirements for minimum h-index thresholds for application for promotion might reduce disparities between rank and scientific contributions. We encourage use of the h-index for tracking academic progression and as a parameter to consider in academic promotion.

Academic promotion requires evidence of scholastic production. The number of publications by a scientist is the most frequently reported metric of scholastic production, but it does not account for the impact of publications. The h-index is a bibliometric measure that combines both volume and impact of scientific contributions. The physicist Jorge E. Hirsch introduced this metric in 2005.¹ He defined it as the number of publications (h) by an author that have been cited at least h times. For example, a scientist with 30 publications including 12 that have been cited at least 12 times each has an h-index of 12. h-Index is a superior predictor of future scientific achievement in physics compared with total citation count, total publication count, and citations per publication. Hirsch² proposed h-index thresholds of 12 and 18 for advancement to associate professor and full professor in physics, respectively.²

h-Index values are not comparable across academic disciplines because they are influenced by the number of journals and authors within the field. Scientists in disciplines with numerous scholars and publications will have higher h-indices. For example, the mean h-index for full professors of cardiothoracic anesthesiology is 12, but the mean h-index for full professors of urology is 22.^3,4 Hence, h-index thresholds for professional advancement cannot be generalized but must be calculated on a granular, specialty-specific basis.

In a prior study on h-index among academic dermatologists in the United States, John et al⁵ reported that fellowship-trained dermatologists had a significantly higher mean h-index than those without fellowship training (13.2 vs 11.7; P<.001). They further found the mean h-index increased with academic rank.⁵

In our study, we measured mean and median h-indices among associate and full professors of dermatology in academic training programs in the United States with the goal of describing h-index distributions in these 2 academic ranks. We further sought to measure regional differences in h-index between northeastern, southern, central, and western states as defined by the National Resident Matching Program.

Methods

Institutional review board approval was deferred because the study did not require patient information or participation. Using the Association of American Medical Colleges Electronic Residency Application Service website (https://www.aamc.org/services/eras/) we identified dermatology residency training programs accredited by the Accreditation Council for Graduate Medical Education and participating in the Electronic Residency Application Service for the National Resident Matching Program in the United States. We visited the official website of each residency program and identified all associate and full professors of dermatology for further study. We included all faculty members listed as professor, clinical professor, associate professor, or clinical associate professor, and excluded assistant professor, volunteer faculty, research professor, and research associate professor. All faculty held an MD degree or an equivalent degree, such as MBBS or MDCM.

We used the Thomson Reuters (now Clarivate Analytics) Web of Science to calculate h-index and publication counts. The initial search was basic using the professor’s last name and first initial. We then augmented this list by searching for all variations of each professor’s name, with or without middle initial. Each publication in the search results was confirmed as belonging to the author of interest by verifying coauthors, institution information, and subject material. For authors with common names, we additionally consulted their online university profiles for specific names used in their “Selected Publications” lists. In a minority of cases, we also limited Research Domain to “dermatology.” Referring to the verified publication list for each dermatology professor, we used the Web of Science Citation Report function to determine number of publications and h-index for the individual. We tabulated results for associate and full professors and subgrouped those results into 4 geographic regions—northeastern, southern, central, and western states—according to the map used by the National Resident Matching Program. Descriptive statistics were performed with Microsoft Excel.

Results

We identified 300 associate professors and 352 full professors from 81 academic institutions. The number of associate professors per institution ranged from 1 to 25; the number of full professors per institution ranged from 1 to 16. The median and mean h-indices for associate and full professors, including interquartile values, are shown in the Table. There was a broad range of h-index scores among both academic ranks; median and mean h-indices varied more than 5-fold between the bottom and upper quartiles in both associate and full professor cohorts. Median interquartile h-index values for upper-quartile associate professors overlapped with those of lower-quartile full professors (Figure 1). h-Index for associate and full professors was similar across the 4 regions defined by the National Resident Matching Program. Median h-index was highest for full professors in western states and lowest for associate professors in southern states (Figure 2).

Comment

Professional advancement in academic medicine requires scholastic production. The h-index, defined as the number of publications (h) that have been cited at least h times, is a bibliometric measure that accounts for both volume and impact of an individual’s scientific productivity. The h-index would be a useful tool for determining professional advancement in academic dermatology departments. In this project, we calculated h-index values for 300 associate professors and 352 full professors of dermatology in the United States. We found the median h-index for associate professors was 8 and the median h-index for full professors was 21. There was more than a 5-fold variation in median and mean h-indices between lower and upper quartiles within both the associate and full professor cohorts. The highest median and mean h-indices were found among full professors of dermatology in western states. These results provide the opportunity for academic dermatologists and institutions to compare their research contributions with peers across the United States.

Our results support those of John et al⁵ who also found academic rank in dermatology was correlated with h-index. Scopus, Web of Science, and Google Scholar can be used to calculate h-index, but they may return different scores for the same individual.⁶ John et al⁵ used the Scopus database to calculate h-index. We used Web of Science because Scopus only includes citations since 1996 and Web of Science was used in the original h-index studies by Hirsch.^1,2 Institutions that adopt h-index criteria for advancement and resource distribution decisions should be aware that database selection can affect h-index scores.

Caveats With the h-Index
Flaws in the h-index include inflationary effects of self-citation, time bias, and excessive coauthorship. Individuals can increase their h-index by routinely citing their own publications. However, Engqvist and Frommen⁷ found tripling self-citations increased the h-index by only 1.

Citations tend to increase with time, and authors who have been active for longer periods will have a higher h-index. It is more difficult for junior faculty to distinguish themselves with the h-index, as it takes time for even the most impactful publications to gain citations. Major scientific papers can take years from conception to publication, and an outstanding paper that is 1 year old would have fewer citations than an equally impactful paper that is 10 years old. To adjust for the effect of time bias, Hirsch² proposed the m-index, in which the h-index is divided by the years between the author’s first and last publication. He proposed that an m-index of 1 would indicate a successful scientist, 2 an outstanding scientist, and 3 a unique individual.²

The literature is increasingly dominated by teams of coauthors, and the number of coauthors within each team has increased over the last 5 decades.⁸ h-Indices will increase if this trend continues, making it difficult to compare h-indices between different eras. Prosperi et al⁹ found national differences in kinship-based coauthorship, suggesting nepotism may influence decisions in assigning authorship status. h-Index valuations do not require evidence of meaningful contribution to the work but simply rely on contributors’ self-governance in assigning authorship status.

The h-index also has a bias against highly cited papers. A scientist with a small number of highly influential papers may have a smaller h-index than a scientist with more papers of modest impact. Finally, an author who has changed names (eg, due to marriage) may have an artificially low h-index, as a standard database search would miss publications under a maiden name.

Limitations
This study is limited by possible operator error when compiling each author’s publication list through Web of Science. Our search and refinement methodology took into account that authors may publish with slight variations in name, in various subject areas and fields, and with different institutions and coauthors. Each publication populated through Web of Science was carefully verified by the principal investigator; however, overestimation or underestimation of the number of publications and citations was possible, as the publication lists were not verified by the studied associate and full professors themselves. Our results are consistent with the h-index bar charts published by John et al⁵ using an alternate citation index, Scopus, which tends to corroborate our findings. This study also is limited by possible time bias because we did not correct the h-index for years of active publication (m-index).

Conclusion

In summary, we found the median h-index for associate professors was 8 and the median h-index for full professors was 21. We found a broad range of h-index values within each academic rank. h-Index for upper-quartile associate professors overlapped with those of lower-quartile full professors. Our results suggest professional advancement occurs over a broad range of scholastic production. Adopting requirements for minimum h-index thresholds for application for promotion might reduce disparities between rank and scientific contributions. We encourage use of the h-index for tracking academic progression and as a parameter to consider in academic promotion.

The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Lice are obligate human parasites that have infested humans since antiquity. Pediculosis capitis is an infestation of the scalp by head lice. It is estimated that 6 to 12 million individuals in the United States are affected with head lice per year.¹ Resistance to topical chemical pediculicides is widespread, and new agents have been developed to address this gap in care.

Characteristics of Head Lice

The head louse is a tan-gray–colored, wingless insect measuring approximately 2- to 3-mm long with 3 body segments. It has 6 legs with claws used to grasp individual hairs, and it moves by crawling; it does not fly or jump.^2,3 The head louse has an elongated abdomen and a small head with short antennae and anterior piercing mouthparts (Figure 1).⁴ Nits are transparent, flask-shaped, 0.5- to 0.8-mm egg cases found firmly cemented to the hair shafts approximately 1 to 4 mm above the level of the scalp (Figure 2).⁵ The head louse resides on scalp hair and feeds off the scalp itself. Both lice and nits can be present throughout the scalp but are most commonly found in the postauricular and occipital scalp.^3,4

Female lice live approximately 30 days and lay 5 to 10 eggs per day. Eggs incubate individually in nits laid close to the scalp for 8 to 10 days before hatching.^1,6 The newly hatched nymphs (also called instars) have multiple exoskeletons that are shed as they grow.⁷ Nymphs mature into adults in approximately 2 weeks, and the life cycle begins again.⁸ Head lice are obligate human parasites, feeding approximately every 4 to 6 hours on the blood of the host; however, they can survive up to 4 days without a blood meal on fomites if the climate and conditions are favorable.^5,9

Epidemiology and Transmission

Head lice infestations commonly occur in children aged 3 to 11 years and are more prevalent in girls and women.^1,10 Infestation rates are not reliably recorded, and few population-based studies have been performed; however, it is estimated that 6 to 12 million individuals are infested annually in the United States.¹ Prevalence in some European populations has been estimated to range from 1% to 20%.¹¹ A 2008 literature review found that worldwide prevalence varied across populations from 0.7% to 59%.¹⁰

Transmission occurs most frequently from direct head-to-head contact. One study found that transmission is most likely to occur when hairs are arranged in a parallel alignment and move slowly in relation to one another.¹² Although controversial and probably less notable, transmission also may occur indirectly via fomites or the sharing of hairbrushes, hats, or other headgear.^13,14 Classrooms are a common place for transmission.¹ A 2009 study in Germany found an increase in health department consultations for head lice when schools reopened after vacations. The investigators also found that pediculicide sales peaked from mid-September through October, subsequent to schools reopening after the summer holiday.¹⁵ There is some evidence that overcrowded housing also can lead to increased incidence and transmission.^16,17 There is no consistent correlation of infestation with socioeconomic status.^1,17,18

Clinical Manifestations and Diagnosis

Clinically, patients with head lice present with scalp pruritus and sometimes posterior cervical or occipital lymphadenopathy. Pediculosis also can be asymptomatic. With the first exposure, symptoms may not develop for up to 4 to 6 weeks as the immune system develops sensitivity to the louse saliva.⁶ Bite reactions consisting of papules or wheals are related to immune sensitization.⁵ Louse feces and excoriations from scratching to relieve itch also may be present on examination. Secondary infection of excoriations also is possible.¹

Diagnosis of an active infestation is made by identifying living lice. Because lice move quickly and can be difficult to detect, tightly attached nits on the hair shaft within 4 mm of the scalp are at least indicative of a historic infestation and can be suggestive of active infestation.^1,19 Dermoscopy is a helpful tool in differentiating eggs containing nymphs from the empty cases of hatched lice and also from amorphous pseudonits (hair casts)(Figure 3).^19,20 Wet combing improves the accuracy of diagnosing an active infection.²¹

Treatment

Effective treatment of head lice requires eradication of all living lice as well as louse eggs. Topically applied pyrethroids, including pyrethrin shampoos and mousses and permethrin lotion 1%, are considered the first-line therapy.⁸ Pyrethroids are over-the-counter treatments that act by interfering with sodium transport in the louse, causing depolarization of the neuromembranes and respiratory paralysis.²² Pyrethrins are natural compounds derived from the chrysanthemum plant; permethrin is a synthetic compound. Pyrethrins often are combined with piperonyl butoxide, an insecticide synergist that improves efficacy by inhibiting pyrethrin catabolism.²³ Resistance to pyrethroids has become an increasingly important problem in the United States and worldwide.

Malathion lotion 0.5% is another therapeutic option for head lice. Malathion is a prescription organophosphate cholinesterase inhibitor that also causes respiratory paralysis of the louse and is one of the few treatments that is ovicidal.²² It was withdrawn from the market in 1995 due to its flammability and a theoretical risk of respiratory depression if ingested; however, it was reintroduced in 1999 and remains an effective treatment option with little resistance in the United States.²⁴

Lindane 1% (shampoo and lotion), an organochloride compound that acts by causing neuronal hyperstimulation and eventual paralysis of lice, is no longer recommended due to its serious side effects, including central nervous system toxicity and increased risk of seizure.^8,24

New US Food and Drug Administration–Approved Therapies
Newer topical treatments include benzyl alcohol lotion 5%, spinosad topical suspension 0.9%, ivermectin lotion 0.5%, and dimethicone-based products. Benzyl alcohol was approved by the US Food and Drug Administration (FDA) in 2009 and is available in the United States by prescription.²⁵ Benzyl alcohol kills lice by asphyxiation. Phase 2 and 3 clinical trials showed significant treatment success 1 day posttreatment (fewer live lice than the vehicle alone; P=.004) and 2 weeks posttreatment (absence of live lice compared to the vehicle alone; P=.001).²⁶

Spinosad was approved by the FDA in 2011 and is available in the United States by prescription.²⁵ It contains the compounds spinosyn A and spinosyn D, which are naturally derived through fermentation by the soil bacterium Saccharopolyspora spinosa. It also contains benzyl alcohol. Spinosad paralyzes lice by disrupting neuronal activity and is at least partially ovicidal.²⁷ Phase 3 clinical trials published in 2009 showed that spinosad was significantly more effective than permethrin in eradicating head lice (P<.001).²⁸

Topical ivermectin was approved by the FDA in 2012 for prescription use.²⁵ It acts on chloride ion channels, causing hyperpolarization of the muscle cells of lice and resulting in paralysis and death. Oral ivermectin (200 μg/kg) given once and repeated in 10 days is not FDA approved for the treatment of head lice but has shown some effectiveness and is sometimes used.⁸ A comparison study of topical versus oral ivermectin published in 2014 found that eradication was achieved in 88% (n=27) of topical ivermectin users after 1 treatment and 100% (n=31) after 2 treatments. Oral ivermectin produced cure rates of 45% (n=14) after 1 treatment and 97% (n=30) after 2 treatments. Both topical and oral ivermectin treatments are well tolerated.²⁹

Physically Acting Preparations
Products with a physical mode of action are a new attractive option for treatment of pediculosis because the development of resistance is less likely. Studies of silicone-based fluids that physically occlude the respiratory system of the louse, such as dimethicone liquid gel 4%, have shown superiority over treatment with pyrethroids.^30,31 Although the safety of dimethicone has been demonstrated, silicone-based treatments have not yet been widely adopted in the United States and are not currently used as a first-line treatment.³² However, use of such physically acting pediculicides may in time surpass traditional neurotoxic treatments due to their low susceptibility to resistance and good safety profile.^33,34

Alternative Therapies
Nonchemical treatments for head lice that have shown variable success include wet combing, hot air treatments, and varying occlusive treatments. Physical removal via wet combing requires persistent repeated treatments over several weeks; for example, wet combing may be performed every 3 days for at least 2 weeks or until no head lice are detected on 4 consecutive occasions.³⁵ Cure rates range from 38% to 75% with wet combing as a sole treatment of head lice.³⁶ Because this treatment has minimal risks and no adverse side effects, it can be considered as an alternative treatment for some patients.

Hot air treatments also have been studied. A 2006 study showed that a hot air treatment device had the potential to eradicate head lice, most likely by desiccation. Specifically, 30 minutes of exposure to hot air (at 58.9°F, slightly cooler than a standard hair dryer) using the custom-built device resulted in 98% mortality of eggs and 80% mortality of hatched lice.³⁷ Large randomized controlled trials of hot air treatments have not been performed.

Other alternative treatments include plant-derived oils. A laboratory study of essential oils found that spearmint, cassia, and clove showed pediculicidal activity similar to malathion with improved ovicidal activity.³⁸ However, there is a potential for development of contact dermatitis from essential oils.

Complete Eradication of Head Lice
Removal of nits is an important component of effective lice eradication. Biochemical analysis has revealed that the nit sheath of the head louse is similar in composition to amyloid, rendering it difficult to design products that will unravel the nit sheath while leaving human hair undamaged.³⁹ Because pediculicides are not necessarily ovicidal and complete physical nit removal is difficult to achieve, re-treatment in 7 to 10 days often is advisable to ensure that lice in all stages of the life cycle have been killed.⁴ Treatment of any secondary bacterial infection also is important. Although transmission of lice via fomites is less likely than from head-to-head contact, the cleaning of hats, hairbrushes, and linens is prudent. Diagnosing and treating infested close contacts also is essential to achieving eradication.⁴ Coordinated surveillance, education, and treatment efforts in high-risk communities can help detect asymptomatic cases and control local epidemics in a cost-effective manner.⁴⁰ However, “no nit” policies at schools likely cause a net harm, as nit removal is difficult and children with nonviable nits are then excluded from the classroom.⁵

Treatment Resistance
Resistance to topical neurotoxic treatments is becoming increasingly common.^41-43 Therefore, it is important to identify local patterns of resistance, if possible, when selecting a therapy for head lice. Improper usage, changes in pediculicide formulations and packaging, decreased product efficacy, and natural selection have all contributed to this rise in resistance.⁷ Additionally, due to protection from multiple exoskeletons and the natural molting process as they mature into adults, nymphs may only receive a sublethal dose when exposed to pediculicides, contributing further to resistance.⁷ Resistance to synthetic pyrethroids is most predominant, likely due to selection pressure because permethrin historically has been the most widely used insecticide for pediculosis. A 2014 study found that the frequency of sodium-channel insensitivity to pyrethroids, also known as knockdown resistance (or kdr), in US head louse populations collected over a 10-year period was 84.4% and approached 100% in some communities in recent years.⁴⁴ This evidence strongly supports the use of alternative therapeutic categories to effectively eradicate head lice infestations.

Conclusion

Head lice infestation is common in children, and although it is not harmful to the host, it can be an irritating and symptomatic problem and can lead to notable distress, missed days of school, and secondary infections. Identifying active adult lice is the gold standard for diagnosis. Current recommended treatments include pyrethroids as the first-line therapy; however, resistance to these neurotoxic agents is becoming increasingly common. Alternative therapies such as newer neurotoxic agents or pediculicides with physical mechanisms of action (eg, dimethicone-based products) should be considered, particularly in regions where resistance is known to be high. Education about head lice, proper use of treatment, and coordinated diagnosis are necessary for effective management of this problem.

The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Lice are obligate human parasites that have infested humans since antiquity. Pediculosis capitis is an infestation of the scalp by head lice. It is estimated that 6 to 12 million individuals in the United States are affected with head lice per year.¹ Resistance to topical chemical pediculicides is widespread, and new agents have been developed to address this gap in care.

Characteristics of Head Lice

The head louse is a tan-gray–colored, wingless insect measuring approximately 2- to 3-mm long with 3 body segments. It has 6 legs with claws used to grasp individual hairs, and it moves by crawling; it does not fly or jump.^2,3 The head louse has an elongated abdomen and a small head with short antennae and anterior piercing mouthparts (Figure 1).⁴ Nits are transparent, flask-shaped, 0.5- to 0.8-mm egg cases found firmly cemented to the hair shafts approximately 1 to 4 mm above the level of the scalp (Figure 2).⁵ The head louse resides on scalp hair and feeds off the scalp itself. Both lice and nits can be present throughout the scalp but are most commonly found in the postauricular and occipital scalp.^3,4

Female lice live approximately 30 days and lay 5 to 10 eggs per day. Eggs incubate individually in nits laid close to the scalp for 8 to 10 days before hatching.^1,6 The newly hatched nymphs (also called instars) have multiple exoskeletons that are shed as they grow.⁷ Nymphs mature into adults in approximately 2 weeks, and the life cycle begins again.⁸ Head lice are obligate human parasites, feeding approximately every 4 to 6 hours on the blood of the host; however, they can survive up to 4 days without a blood meal on fomites if the climate and conditions are favorable.^5,9

Epidemiology and Transmission

Head lice infestations commonly occur in children aged 3 to 11 years and are more prevalent in girls and women.^1,10 Infestation rates are not reliably recorded, and few population-based studies have been performed; however, it is estimated that 6 to 12 million individuals are infested annually in the United States.¹ Prevalence in some European populations has been estimated to range from 1% to 20%.¹¹ A 2008 literature review found that worldwide prevalence varied across populations from 0.7% to 59%.¹⁰

Transmission occurs most frequently from direct head-to-head contact. One study found that transmission is most likely to occur when hairs are arranged in a parallel alignment and move slowly in relation to one another.¹² Although controversial and probably less notable, transmission also may occur indirectly via fomites or the sharing of hairbrushes, hats, or other headgear.^13,14 Classrooms are a common place for transmission.¹ A 2009 study in Germany found an increase in health department consultations for head lice when schools reopened after vacations. The investigators also found that pediculicide sales peaked from mid-September through October, subsequent to schools reopening after the summer holiday.¹⁵ There is some evidence that overcrowded housing also can lead to increased incidence and transmission.^16,17 There is no consistent correlation of infestation with socioeconomic status.^1,17,18

Clinical Manifestations and Diagnosis

Clinically, patients with head lice present with scalp pruritus and sometimes posterior cervical or occipital lymphadenopathy. Pediculosis also can be asymptomatic. With the first exposure, symptoms may not develop for up to 4 to 6 weeks as the immune system develops sensitivity to the louse saliva.⁶ Bite reactions consisting of papules or wheals are related to immune sensitization.⁵ Louse feces and excoriations from scratching to relieve itch also may be present on examination. Secondary infection of excoriations also is possible.¹

Diagnosis of an active infestation is made by identifying living lice. Because lice move quickly and can be difficult to detect, tightly attached nits on the hair shaft within 4 mm of the scalp are at least indicative of a historic infestation and can be suggestive of active infestation.^1,19 Dermoscopy is a helpful tool in differentiating eggs containing nymphs from the empty cases of hatched lice and also from amorphous pseudonits (hair casts)(Figure 3).^19,20 Wet combing improves the accuracy of diagnosing an active infection.²¹

Treatment

Effective treatment of head lice requires eradication of all living lice as well as louse eggs. Topically applied pyrethroids, including pyrethrin shampoos and mousses and permethrin lotion 1%, are considered the first-line therapy.⁸ Pyrethroids are over-the-counter treatments that act by interfering with sodium transport in the louse, causing depolarization of the neuromembranes and respiratory paralysis.²² Pyrethrins are natural compounds derived from the chrysanthemum plant; permethrin is a synthetic compound. Pyrethrins often are combined with piperonyl butoxide, an insecticide synergist that improves efficacy by inhibiting pyrethrin catabolism.²³ Resistance to pyrethroids has become an increasingly important problem in the United States and worldwide.

Malathion lotion 0.5% is another therapeutic option for head lice. Malathion is a prescription organophosphate cholinesterase inhibitor that also causes respiratory paralysis of the louse and is one of the few treatments that is ovicidal.²² It was withdrawn from the market in 1995 due to its flammability and a theoretical risk of respiratory depression if ingested; however, it was reintroduced in 1999 and remains an effective treatment option with little resistance in the United States.²⁴

Lindane 1% (shampoo and lotion), an organochloride compound that acts by causing neuronal hyperstimulation and eventual paralysis of lice, is no longer recommended due to its serious side effects, including central nervous system toxicity and increased risk of seizure.^8,24

New US Food and Drug Administration–Approved Therapies
Newer topical treatments include benzyl alcohol lotion 5%, spinosad topical suspension 0.9%, ivermectin lotion 0.5%, and dimethicone-based products. Benzyl alcohol was approved by the US Food and Drug Administration (FDA) in 2009 and is available in the United States by prescription.²⁵ Benzyl alcohol kills lice by asphyxiation. Phase 2 and 3 clinical trials showed significant treatment success 1 day posttreatment (fewer live lice than the vehicle alone; P=.004) and 2 weeks posttreatment (absence of live lice compared to the vehicle alone; P=.001).²⁶

Spinosad was approved by the FDA in 2011 and is available in the United States by prescription.²⁵ It contains the compounds spinosyn A and spinosyn D, which are naturally derived through fermentation by the soil bacterium Saccharopolyspora spinosa. It also contains benzyl alcohol. Spinosad paralyzes lice by disrupting neuronal activity and is at least partially ovicidal.²⁷ Phase 3 clinical trials published in 2009 showed that spinosad was significantly more effective than permethrin in eradicating head lice (P<.001).²⁸

Topical ivermectin was approved by the FDA in 2012 for prescription use.²⁵ It acts on chloride ion channels, causing hyperpolarization of the muscle cells of lice and resulting in paralysis and death. Oral ivermectin (200 μg/kg) given once and repeated in 10 days is not FDA approved for the treatment of head lice but has shown some effectiveness and is sometimes used.⁸ A comparison study of topical versus oral ivermectin published in 2014 found that eradication was achieved in 88% (n=27) of topical ivermectin users after 1 treatment and 100% (n=31) after 2 treatments. Oral ivermectin produced cure rates of 45% (n=14) after 1 treatment and 97% (n=30) after 2 treatments. Both topical and oral ivermectin treatments are well tolerated.²⁹

Physically Acting Preparations
Products with a physical mode of action are a new attractive option for treatment of pediculosis because the development of resistance is less likely. Studies of silicone-based fluids that physically occlude the respiratory system of the louse, such as dimethicone liquid gel 4%, have shown superiority over treatment with pyrethroids.^30,31 Although the safety of dimethicone has been demonstrated, silicone-based treatments have not yet been widely adopted in the United States and are not currently used as a first-line treatment.³² However, use of such physically acting pediculicides may in time surpass traditional neurotoxic treatments due to their low susceptibility to resistance and good safety profile.^33,34

Alternative Therapies
Nonchemical treatments for head lice that have shown variable success include wet combing, hot air treatments, and varying occlusive treatments. Physical removal via wet combing requires persistent repeated treatments over several weeks; for example, wet combing may be performed every 3 days for at least 2 weeks or until no head lice are detected on 4 consecutive occasions.³⁵ Cure rates range from 38% to 75% with wet combing as a sole treatment of head lice.³⁶ Because this treatment has minimal risks and no adverse side effects, it can be considered as an alternative treatment for some patients.

Hot air treatments also have been studied. A 2006 study showed that a hot air treatment device had the potential to eradicate head lice, most likely by desiccation. Specifically, 30 minutes of exposure to hot air (at 58.9°F, slightly cooler than a standard hair dryer) using the custom-built device resulted in 98% mortality of eggs and 80% mortality of hatched lice.³⁷ Large randomized controlled trials of hot air treatments have not been performed.

Other alternative treatments include plant-derived oils. A laboratory study of essential oils found that spearmint, cassia, and clove showed pediculicidal activity similar to malathion with improved ovicidal activity.³⁸ However, there is a potential for development of contact dermatitis from essential oils.

Complete Eradication of Head Lice
Removal of nits is an important component of effective lice eradication. Biochemical analysis has revealed that the nit sheath of the head louse is similar in composition to amyloid, rendering it difficult to design products that will unravel the nit sheath while leaving human hair undamaged.³⁹ Because pediculicides are not necessarily ovicidal and complete physical nit removal is difficult to achieve, re-treatment in 7 to 10 days often is advisable to ensure that lice in all stages of the life cycle have been killed.⁴ Treatment of any secondary bacterial infection also is important. Although transmission of lice via fomites is less likely than from head-to-head contact, the cleaning of hats, hairbrushes, and linens is prudent. Diagnosing and treating infested close contacts also is essential to achieving eradication.⁴ Coordinated surveillance, education, and treatment efforts in high-risk communities can help detect asymptomatic cases and control local epidemics in a cost-effective manner.⁴⁰ However, “no nit” policies at schools likely cause a net harm, as nit removal is difficult and children with nonviable nits are then excluded from the classroom.⁵

Treatment Resistance
Resistance to topical neurotoxic treatments is becoming increasingly common.^41-43 Therefore, it is important to identify local patterns of resistance, if possible, when selecting a therapy for head lice. Improper usage, changes in pediculicide formulations and packaging, decreased product efficacy, and natural selection have all contributed to this rise in resistance.⁷ Additionally, due to protection from multiple exoskeletons and the natural molting process as they mature into adults, nymphs may only receive a sublethal dose when exposed to pediculicides, contributing further to resistance.⁷ Resistance to synthetic pyrethroids is most predominant, likely due to selection pressure because permethrin historically has been the most widely used insecticide for pediculosis. A 2014 study found that the frequency of sodium-channel insensitivity to pyrethroids, also known as knockdown resistance (or kdr), in US head louse populations collected over a 10-year period was 84.4% and approached 100% in some communities in recent years.⁴⁴ This evidence strongly supports the use of alternative therapeutic categories to effectively eradicate head lice infestations.

Conclusion

Head lice infestation is common in children, and although it is not harmful to the host, it can be an irritating and symptomatic problem and can lead to notable distress, missed days of school, and secondary infections. Identifying active adult lice is the gold standard for diagnosis. Current recommended treatments include pyrethroids as the first-line therapy; however, resistance to these neurotoxic agents is becoming increasingly common. Alternative therapies such as newer neurotoxic agents or pediculicides with physical mechanisms of action (eg, dimethicone-based products) should be considered, particularly in regions where resistance is known to be high. Education about head lice, proper use of treatment, and coordinated diagnosis are necessary for effective management of this problem.

The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Lice are obligate human parasites that have infested humans since antiquity. Pediculosis capitis is an infestation of the scalp by head lice. It is estimated that 6 to 12 million individuals in the United States are affected with head lice per year.¹ Resistance to topical chemical pediculicides is widespread, and new agents have been developed to address this gap in care.

Characteristics of Head Lice

The head louse is a tan-gray–colored, wingless insect measuring approximately 2- to 3-mm long with 3 body segments. It has 6 legs with claws used to grasp individual hairs, and it moves by crawling; it does not fly or jump.^2,3 The head louse has an elongated abdomen and a small head with short antennae and anterior piercing mouthparts (Figure 1).⁴ Nits are transparent, flask-shaped, 0.5- to 0.8-mm egg cases found firmly cemented to the hair shafts approximately 1 to 4 mm above the level of the scalp (Figure 2).⁵ The head louse resides on scalp hair and feeds off the scalp itself. Both lice and nits can be present throughout the scalp but are most commonly found in the postauricular and occipital scalp.^3,4

Female lice live approximately 30 days and lay 5 to 10 eggs per day. Eggs incubate individually in nits laid close to the scalp for 8 to 10 days before hatching.^1,6 The newly hatched nymphs (also called instars) have multiple exoskeletons that are shed as they grow.⁷ Nymphs mature into adults in approximately 2 weeks, and the life cycle begins again.⁸ Head lice are obligate human parasites, feeding approximately every 4 to 6 hours on the blood of the host; however, they can survive up to 4 days without a blood meal on fomites if the climate and conditions are favorable.^5,9

Epidemiology and Transmission

Head lice infestations commonly occur in children aged 3 to 11 years and are more prevalent in girls and women.^1,10 Infestation rates are not reliably recorded, and few population-based studies have been performed; however, it is estimated that 6 to 12 million individuals are infested annually in the United States.¹ Prevalence in some European populations has been estimated to range from 1% to 20%.¹¹ A 2008 literature review found that worldwide prevalence varied across populations from 0.7% to 59%.¹⁰

Transmission occurs most frequently from direct head-to-head contact. One study found that transmission is most likely to occur when hairs are arranged in a parallel alignment and move slowly in relation to one another.¹² Although controversial and probably less notable, transmission also may occur indirectly via fomites or the sharing of hairbrushes, hats, or other headgear.^13,14 Classrooms are a common place for transmission.¹ A 2009 study in Germany found an increase in health department consultations for head lice when schools reopened after vacations. The investigators also found that pediculicide sales peaked from mid-September through October, subsequent to schools reopening after the summer holiday.¹⁵ There is some evidence that overcrowded housing also can lead to increased incidence and transmission.^16,17 There is no consistent correlation of infestation with socioeconomic status.^1,17,18

Clinical Manifestations and Diagnosis

Clinically, patients with head lice present with scalp pruritus and sometimes posterior cervical or occipital lymphadenopathy. Pediculosis also can be asymptomatic. With the first exposure, symptoms may not develop for up to 4 to 6 weeks as the immune system develops sensitivity to the louse saliva.⁶ Bite reactions consisting of papules or wheals are related to immune sensitization.⁵ Louse feces and excoriations from scratching to relieve itch also may be present on examination. Secondary infection of excoriations also is possible.¹

Diagnosis of an active infestation is made by identifying living lice. Because lice move quickly and can be difficult to detect, tightly attached nits on the hair shaft within 4 mm of the scalp are at least indicative of a historic infestation and can be suggestive of active infestation.^1,19 Dermoscopy is a helpful tool in differentiating eggs containing nymphs from the empty cases of hatched lice and also from amorphous pseudonits (hair casts)(Figure 3).^19,20 Wet combing improves the accuracy of diagnosing an active infection.²¹

Treatment

Effective treatment of head lice requires eradication of all living lice as well as louse eggs. Topically applied pyrethroids, including pyrethrin shampoos and mousses and permethrin lotion 1%, are considered the first-line therapy.⁸ Pyrethroids are over-the-counter treatments that act by interfering with sodium transport in the louse, causing depolarization of the neuromembranes and respiratory paralysis.²² Pyrethrins are natural compounds derived from the chrysanthemum plant; permethrin is a synthetic compound. Pyrethrins often are combined with piperonyl butoxide, an insecticide synergist that improves efficacy by inhibiting pyrethrin catabolism.²³ Resistance to pyrethroids has become an increasingly important problem in the United States and worldwide.

Malathion lotion 0.5% is another therapeutic option for head lice. Malathion is a prescription organophosphate cholinesterase inhibitor that also causes respiratory paralysis of the louse and is one of the few treatments that is ovicidal.²² It was withdrawn from the market in 1995 due to its flammability and a theoretical risk of respiratory depression if ingested; however, it was reintroduced in 1999 and remains an effective treatment option with little resistance in the United States.²⁴

Lindane 1% (shampoo and lotion), an organochloride compound that acts by causing neuronal hyperstimulation and eventual paralysis of lice, is no longer recommended due to its serious side effects, including central nervous system toxicity and increased risk of seizure.^8,24

New US Food and Drug Administration–Approved Therapies
Newer topical treatments include benzyl alcohol lotion 5%, spinosad topical suspension 0.9%, ivermectin lotion 0.5%, and dimethicone-based products. Benzyl alcohol was approved by the US Food and Drug Administration (FDA) in 2009 and is available in the United States by prescription.²⁵ Benzyl alcohol kills lice by asphyxiation. Phase 2 and 3 clinical trials showed significant treatment success 1 day posttreatment (fewer live lice than the vehicle alone; P=.004) and 2 weeks posttreatment (absence of live lice compared to the vehicle alone; P=.001).²⁶

Spinosad was approved by the FDA in 2011 and is available in the United States by prescription.²⁵ It contains the compounds spinosyn A and spinosyn D, which are naturally derived through fermentation by the soil bacterium Saccharopolyspora spinosa. It also contains benzyl alcohol. Spinosad paralyzes lice by disrupting neuronal activity and is at least partially ovicidal.²⁷ Phase 3 clinical trials published in 2009 showed that spinosad was significantly more effective than permethrin in eradicating head lice (P<.001).²⁸

Topical ivermectin was approved by the FDA in 2012 for prescription use.²⁵ It acts on chloride ion channels, causing hyperpolarization of the muscle cells of lice and resulting in paralysis and death. Oral ivermectin (200 μg/kg) given once and repeated in 10 days is not FDA approved for the treatment of head lice but has shown some effectiveness and is sometimes used.⁸ A comparison study of topical versus oral ivermectin published in 2014 found that eradication was achieved in 88% (n=27) of topical ivermectin users after 1 treatment and 100% (n=31) after 2 treatments. Oral ivermectin produced cure rates of 45% (n=14) after 1 treatment and 97% (n=30) after 2 treatments. Both topical and oral ivermectin treatments are well tolerated.²⁹

Physically Acting Preparations
Products with a physical mode of action are a new attractive option for treatment of pediculosis because the development of resistance is less likely. Studies of silicone-based fluids that physically occlude the respiratory system of the louse, such as dimethicone liquid gel 4%, have shown superiority over treatment with pyrethroids.^30,31 Although the safety of dimethicone has been demonstrated, silicone-based treatments have not yet been widely adopted in the United States and are not currently used as a first-line treatment.³² However, use of such physically acting pediculicides may in time surpass traditional neurotoxic treatments due to their low susceptibility to resistance and good safety profile.^33,34

Alternative Therapies
Nonchemical treatments for head lice that have shown variable success include wet combing, hot air treatments, and varying occlusive treatments. Physical removal via wet combing requires persistent repeated treatments over several weeks; for example, wet combing may be performed every 3 days for at least 2 weeks or until no head lice are detected on 4 consecutive occasions.³⁵ Cure rates range from 38% to 75% with wet combing as a sole treatment of head lice.³⁶ Because this treatment has minimal risks and no adverse side effects, it can be considered as an alternative treatment for some patients.

Hot air treatments also have been studied. A 2006 study showed that a hot air treatment device had the potential to eradicate head lice, most likely by desiccation. Specifically, 30 minutes of exposure to hot air (at 58.9°F, slightly cooler than a standard hair dryer) using the custom-built device resulted in 98% mortality of eggs and 80% mortality of hatched lice.³⁷ Large randomized controlled trials of hot air treatments have not been performed.

Other alternative treatments include plant-derived oils. A laboratory study of essential oils found that spearmint, cassia, and clove showed pediculicidal activity similar to malathion with improved ovicidal activity.³⁸ However, there is a potential for development of contact dermatitis from essential oils.

Complete Eradication of Head Lice
Removal of nits is an important component of effective lice eradication. Biochemical analysis has revealed that the nit sheath of the head louse is similar in composition to amyloid, rendering it difficult to design products that will unravel the nit sheath while leaving human hair undamaged.³⁹ Because pediculicides are not necessarily ovicidal and complete physical nit removal is difficult to achieve, re-treatment in 7 to 10 days often is advisable to ensure that lice in all stages of the life cycle have been killed.⁴ Treatment of any secondary bacterial infection also is important. Although transmission of lice via fomites is less likely than from head-to-head contact, the cleaning of hats, hairbrushes, and linens is prudent. Diagnosing and treating infested close contacts also is essential to achieving eradication.⁴ Coordinated surveillance, education, and treatment efforts in high-risk communities can help detect asymptomatic cases and control local epidemics in a cost-effective manner.⁴⁰ However, “no nit” policies at schools likely cause a net harm, as nit removal is difficult and children with nonviable nits are then excluded from the classroom.⁵

Treatment Resistance
Resistance to topical neurotoxic treatments is becoming increasingly common.^41-43 Therefore, it is important to identify local patterns of resistance, if possible, when selecting a therapy for head lice. Improper usage, changes in pediculicide formulations and packaging, decreased product efficacy, and natural selection have all contributed to this rise in resistance.⁷ Additionally, due to protection from multiple exoskeletons and the natural molting process as they mature into adults, nymphs may only receive a sublethal dose when exposed to pediculicides, contributing further to resistance.⁷ Resistance to synthetic pyrethroids is most predominant, likely due to selection pressure because permethrin historically has been the most widely used insecticide for pediculosis. A 2014 study found that the frequency of sodium-channel insensitivity to pyrethroids, also known as knockdown resistance (or kdr), in US head louse populations collected over a 10-year period was 84.4% and approached 100% in some communities in recent years.⁴⁴ This evidence strongly supports the use of alternative therapeutic categories to effectively eradicate head lice infestations.

Conclusion

Head lice infestation is common in children, and although it is not harmful to the host, it can be an irritating and symptomatic problem and can lead to notable distress, missed days of school, and secondary infections. Identifying active adult lice is the gold standard for diagnosis. Current recommended treatments include pyrethroids as the first-line therapy; however, resistance to these neurotoxic agents is becoming increasingly common. Alternative therapies such as newer neurotoxic agents or pediculicides with physical mechanisms of action (eg, dimethicone-based products) should be considered, particularly in regions where resistance is known to be high. Education about head lice, proper use of treatment, and coordinated diagnosis are necessary for effective management of this problem.

The approach to the treatment of common skin disorders and cosmetic concerns in patients with skin of color (SOC) requires the clinician to understand the biological differences, nuances, and special considerations that are unique to patients with darker skin types.^1-3 This article addresses 4 common facial concerns in SOC patients—acne, rosacea, facial hyperpigmentation, and cosmetic enhancement—and provides treatment recommendations and management pearls to assist the clinician with optimal outcomes for SOC patients.

Acne in SOC Patients

Acne vulgaris is one of the most common conditions that dermatologists treat and is estimated to affect 40 to 50 million individuals in the United States.¹ Many of these acne patients are individuals with SOC.^2-4 A study of 2835 females (aged 10–70 years) conducted in 4 different cities—Los Angeles, California; London, United Kingdom; Akita, Japan; and Rome, Italy—demonstrated acne prevalence of 37% in blacks, 32% in Hispanics, 30% in Asians, 24% in whites, and 23% in Continental Indians.⁵ Blacks, Hispanics, and Continental Indians demonstrated equal prevalence with comedonal and inflammatory acne. Asians displayed more inflammatory acne lesions than comedones. In contrast, whites demonstrated more comedones than inflammatory acne. Dyspigmentation, postinflammatory hyperpigmentation (PIH), and atrophic scars were more common in black and Hispanic females than other ethnicities.⁵ This study illustrated that acne-induced PIH is a common sequela in SOC patients and is the main reason they seek treatment.^6,7

The pathogenesis of acne is the same in all racial and ethnic groups: (1) follicular hyperkeratinization and the formation of a microcomedone caused by abnormal desquamation of the keratinocytes within the sebaceous follicle, (2) production of sebum by circulating androgens, (3) proliferation of Propionibacterium acnes, and (4) inflammation. Subclinical inflammation is present throughout all stages of acne, including normal-appearing skin, inflammatory lesions, comedones, and scarring, and may contribute to PIH in acne patients with SOC (Figure 1).⁸ A thorough history should be obtained from acne patients, including answers to the following questions⁷:

• What skin and hair care products do you use?
• Do you use sunscreen daily?
• What cosmetic products or makeup do you use?
• Do you use any ethnic skin care products, including skin lightening creams?
• Do you have a history of keloids?

It is important to ask these questions to assess if the SOC patient has developed pomade acne,⁹ acne cosmetica,¹⁰ or a potential risk of skin irritation from the use of skin care practices. It is best to take total control of the patient’s skin care regimen and discontinue use of toners, astringents, witch hazel, exfoliants, and rubbing alcohol, which may lead to skin dryness and irritation, particularly when combined with topical acne medications.

Treatment
Treatment of acne in SOC patients is similar to generally recommended treatments, with special considerations. Consider the following key points when treating acne in SOC patients:

• Treat acne early and aggressively to prevent or minimize subsequent PIH and acne scarring.
• Balance aggressive treatment with nonirritating topical skin care.
• Most importantly, target PIH in addition to acne and choose a regimen that limits skin irritation that might exacerbate existing PIH.⁷

Develop a maintenance program to control future breakouts. Topical agents can be used as monotherapy or in fixed combinations and may include benzoyl peroxide, antibiotics, dapsone, azelaic acid (AZA), and retinoids. Similar to white patients, topical retinoids remain a first-line treatment for acne in patients with SOC.^11,12

Tolerability must be managed in SOC acne patients. Therapeutic maneuvers that can be instituted should include a discussion on using gentle skin care, initiating therapy with a retinoid applied every other night starting with a low concentration and gradually titrating up, and applying a moisturizer before or after applying acne medication. Oral therapies consist of antibiotics (doxycycline, minocycline), retinoids (isotretinoin), and hormonal modulators (oral contraceptives, spironolactone). Isotretinoin, recommended for patients with nodulocystic acne, may play a possible role in treating acne-induced PIH.¹³

Two common procedural therapies for acne include comedone extraction and intralesional corticosteroid injection. A 6- to 8-week course of a topical retinoid prior to comedonal extraction may facilitate the procedure and is recommended in SOC patients to help reduce cutaneous trauma and PIH.¹¹ Inflammatory acne lesions can be treated with intralesional injection of triamcinolone acetonide 2.5 or 5.0 mg/mL, which usually reduces inflammation within 2 to 5 days.¹¹

Treatment of acne-induced PIH includes sun protection, topical and oral medications, chemical peels, lasers, and energy devices. Treatment of hypertrophic scarring and keloids involves intralesional injection of triamcinolone acetonide 20, 30, or 40 mg/mL every 4 weeks until the lesion is flat.¹¹

Superficial chemical peels can be used to treat acne and PIH in SOC patients,¹⁴ such as salicylic acid (20%–30%), glycolic acid (20%–70%), trichloroacetic acid (15%–30%), and Jessner peels.

Acne Scarring
Surgical approaches to acne scarring in patients with SOC include elliptical excision, punch excision, punch elevation, punch autografting, dermal grafting, dermal planning, subcutaneous incision (subcision), dermabrasion, microneedling, fillers, and laser skin resurfacing. The treatment of choice depends on the size, type, and depth of the scar and the clinician’s preference.

Lasers
Fractional photothermolysis has emerged as a treatment option for acne scars in SOC patients. This procedure produces microscopic columns of thermal injury in the epidermis and dermis, sparing the surrounding tissue and minimizing downtime and adverse events. Because fractional photothermolysis does not target melanin and produces limited epidermal injury, darker Fitzpatrick skin types (IV–VI) can be safely and effectively treated with this procedure.¹⁵

Rosacea in SOC Patients

Rosacea is a chronic inflammatory disorder that affects the vasculature and pilosebaceous units of the face. It commonly is seen in Fitzpatrick skin types I and II; however, rosacea can occur in all skin types (Figure 2). Triggers include emotional stress, extreme environmental temperatures, hot and spicy foods, red wine or alcohol, and topical irritants or allergens found in common cosmetic products.¹⁶

Data suggest that 4% of rosacea patients in the United States are of African, Latino, or Asian descent.¹¹ National Ambulatory Medical Care Survey data revealed that of 31.5 million rosacea visits, 2% of patients were black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino. In a 5-year longitudinal study of 2587 rosacea patients enrolled in Medicaid in North Carolina who were prescribed at least 1 topical treatment for rosacea, 16.27% were black and 10% were of a race other than white.¹⁷

Although the pathogenesis of rosacea is unclear, hypotheses include immune system abnormalities, neurogenic dysregulation, presence of microorganisms (eg, Demodex folliculorum), UV damage, and skin barrier dysfunction.¹⁸

The 4 major subtypes of rosacea are erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea.¹⁶ Interestingly, rosacea in SOC patients may present with hypopigmentation surrounding the borders of the facial erythema. For phymatous rosacea, isotretinoin may reduce incipient rhinophyma but must be carefully monitored and pregnancy must be excluded. Surgical or laser therapy may be indicated to recontour the nose if severe.

There are several skin conditions that can present with facial erythema in patients with SOC, including seborrheic dermatitis, systemic lupus erythematosus, and contact dermatitis. It is important to note that the detection of facial erythema in darker skin types may be difficult; therefore, laboratory evaluation (antinuclear antibodies), patch testing, and skin biopsy should be considered if the clinical diagnosis is unclear.

Treatment
Treatment of rosacea in SOC patients does not differ from other racial groups. Common strategies include gentle skin care, sun protection (sun protection factor 30+), and barrier repair creams. Topical agents include metronidazole, AZA, sodium sulfacetamide/sulfur, ivermectin, and retinoids.¹⁶ Oral treatments include antibiotics in the tetracycline family (eg, subantimicrobial dose doxycycline) and isotretinoin.¹⁶ Persistent erythema associated with rosacea can be treated with brimonidine¹⁹ and oxymetazoline.²⁰ Vascular lasers and intense pulsed light may be used to address the vascular components of rosacea²¹; however, the latter is not recommended in Fitzpatrick skin types IV through VI.

Facial Hyperpigmentation in SOC Patients

Hyperpigmentation disorders can be divided into conditions that affect Fitzpatrick skin types I through III and IV though VI. Mottled hyperpigmentation (photodamage) and solar lentigines occur in patients with lighter skin types as compared to melasma, PIH, and age-related (UV-induced) hyperpigmentation, which occur more commonly in patients with darker skin types. Facial hyperpigmentation is a common concern in SOC patients. In a survey of cosmetic concerns of 100 women with SOC, hyperpigmentation or dark spots (86%) and blotchy uneven skin (80%) were the top concerns.²² In addition, facial hyperpigmentation has been shown to negatively impact quality of life.²³

Postinflammatory hyperpigmentation occurs from a pathophysiological response to inflammation, cutaneous irritation or injury, and subsequent melanocyte lability. Postinflammatory hyperpigmentation is a common presenting concern in patients with SOC and is seen as a result of many inflammatory skin disorders (eg, acne, eczema) and dermatologic procedures (eg, adverse reaction to electrodesiccation, microdermabrasion, chemical peels, laser surgery).²⁴

Melasma is an acquired idiopathic disorder of hyperpigmentation and often referred to as the mask of pregnancy (Figure 3). It occurs on sun-exposed areas of skin, mainly in women with Fitzpatrick skin types III through V. Associated factors or triggers include pregnancy, hormonal treatments, exposure to UV radiation, and medications.²⁵ Hereditary factors play a role in more than 40% of cases.²⁶

Other not-so-common facial dyschromias include contact dermatitis, acanthosis nigricans, exogenous ochronosis, lichen planus pigmentosus (associated with frontal fibrosing alopecia),²⁷ drug-induced hyperpigmentation (associated with minocycline or diltiazem),^28,29 and UV-induced (age-related) hyperpigmentation.

Treatment
The treatment of hyperpigmentation should provide the following: (1) protection from sun exposure; (2) inhibition of tyrosinase, the enzyme responsible for the conversion of tyrosine to melanin; (3) inhibition of melanosome transfer from the melanocyte to the keratinocyte; (4) removal of melanin from the epidermis through exfoliation; and (5) destruction or disruption of melanin in the dermis.³⁰ Therapies for facial hyperpigmentation are listed in Table 1.

Topical therapies include prescription medications and nonprescription cosmeceuticals. Prescription medications include hydroquinone (HQ), topical retinoids, and AZA. Hydroquinone, a tyrosinase inhibitor, is the gold standard for skin lightening and often is used as a first-line therapy. It is used as a monotherapy (HQ 4%) or as a fixed combination with tretinoin 0.05% and fluocinolone 0.01%.³¹ Use caution with HQ in high concentrations (6% and higher) and low concentrations (2% [over-the-counter strength]) used long-term due to the potential risk of exogenous ochronosis.

Topical retinoids have been shown to be effective therapeutic agents for melasma and PIH. Tretinoin,³² tazarotene,³³ and adapalene³⁴ all have demonstrated efficacy for acne and acne-induced PIH in SOC patients. Patients must be monitored for the development of retinoid dermatitis and worsening of hyperpigmentation.

Azelaic acid is a naturally occurring dicarboxylic acid obtained from cultures of Malassezia furfur. Azelaic acid inhibits tyrosinase activity, DNA synthesis, and mitochondrial enzymes, thus blocking direct cytotoxic effects toward melanocytes. Azelaic acid is approved by the US Food and Drug Administration for acne in a 20% cream formulation and rosacea in 15% gel and foam formulations, and it is used off label for melasma and PIH.³⁵

Oral tranexamic acid is currently used as a hemostatic agent due to its ability to inhibit the plasminogen-plasmin pathway. In melasma, it blocks the interaction between melanocytes and keratinocytes in the epidermis and modulates the vascular component of melasma in the dermis. In an open-label study, 561 Asian melasma patients were treated with oral tranexamic acid 250 mg twice daily for 4 months. Results demonstrated improvement in 90% of patients, and 7.1% reported adverse effects (eg, abdominal bloating and pain, nausea, vomiting, headache, tinnitus, numbness, menstrual irregularities).³⁶ Coagulation screening should be monitored monthly, and any patient with a history of clotting abnormalities should be excluded from off-label treatment with oral tranexamic acid.

Nonprescription cosmeceuticals are available over-the-counter or are office dispensed.³⁷ For optimal results, cosmeceutical agents for skin lightening are used in combination. Most of these combinations are HQ free and have additive benefits such as a multimodal skin lightening agent containing key ingredients that correct and prevent skin pigmentation via several pathways affecting melanogenesis.³⁸ It is an excellent alternative to HQ for mottled and diffuse UV-induced hyperpigmentation and can be used for maintenance therapy in patients with melasma.

Photoprotection is an essential component of therapy for melasma and PIH, but there is a paucity of data on the benefits for SOC patients. Halder et al³⁹ performed a randomized prospective study of 89 black and Hispanic patients who applied sunscreen with a sun protection factor of 30 or 60 daily for 8 weeks. Clinical grading, triplicate L*A*B chromameter, and clinical photography were taken at baseline and weeks 4 and 8. The results demonstrated skin lightening in both black and Hispanic patients and support the use of sunscreen in the prevention and management of dyschromia in SOC patients.³⁹ Visible light also may play a role in melasma development, and thus use of sunscreens or makeup containing iron oxides are recommended.⁴⁰

Procedural treatments for facial hyperpigmentation include microdermabrasion, chemical peels, lasers, energy-based devices, and microneedling. There are many types and formulations of chemical peeling agents available; however, superficial and medium-depth chemical peels are recommended for SOC patients (Table 2). Deep chemical peels are not recommended for SOC patients due to the potential increased risk for PIH and scarring.

Cosmetic Enhancement in SOC Patients

Cosmetic procedures are gaining popularity in the SOC population and account for more than 20% of cosmetic procedures in the United States.⁴¹ Facial cosmetic concerns in SOC include dyschromia, benign growths (dermatosis papulosa nigra), hyperkinetic facial lines, volume loss, and skin laxity.⁴² Key principles to consider when treating SOC patients are the impact of ethnicity on aging and facial structure, the patient’s desired cosmetic outcome, tissue reaction to anticipated treatments, and the patient’s expectations for recommended therapies.

Aging in SOC Patients
Skin aging can be classified as intrinsic aging or extrinsic aging. Intrinsic aging is genetic and involves subsurface changes such as volume loss, muscle atrophy, and resorption of bony structure. Extrinsic aging (or photoaging) involves surface changes of the epidermis/dermis and manifests as mottled pigmentation, textural changes, and fine wrinkling. Due to the photoprotection of melanin (black skin=SPF 13.4), skin aging in SOC patients is delayed by 10 to 20 years.⁴³ In addition, SOC patients have more reactive collagen and can benefit from noninvasive cosmetic procedures such as fillers and skin-tightening procedures.⁴²

Cosmetic Treatments and Procedures
Dermatosis papulosa nigra (benign growths of skin that have a genetic predisposition)⁴⁴ occur mainly on the face but can involve the entire body. Treatment modalities include electrodesiccation, cryotherapy, scissor excision, and laser surgery.⁴⁵

Treatment of hyperkinetic facial lines with botulinum toxin type A is a safe and effective procedure in patients with SOC. Grimes and Shabazz⁴⁶ performed a 4-month, randomized, double-blind study that evaluated the treatment of glabellar lines in women with Fitzpatrick skin types V and VI. The results demonstrated that the duration of effects was the same in the patients who received either 20 or 30 U of botulinum toxin type A.⁴⁶ Dynamic rhytides (furrows and frown/scowl lines arising from laughing, frowning, or smiling) can be treated safely in patients with SOC using botulinum toxin type A off label for relaxation of the upper and lower hyperkinetic muscles that result in these unwanted signs of aging. Botulinum toxin type A often is used for etched-in crow’s-feet, which rarely are evident in SOC patients.⁴⁷ Facial shaping also can be accomplished by injecting botulinum toxin type A in combination with soft-tissue dermal fillers.⁴⁷

Although black individuals do not experience perioral rhytides at the frequency of white individuals, they experience a variety of other cosmetic issues related to skin sagging and sinking. Currently available hyaluronic acid (HA) fillers have been shown to be safe in patients with Fitzpatrick skin types IV through VI.⁴⁸ Two studies evaluated fillers in patients with SOC, specifically HA⁴⁹ and calcium hydroxylapatite,⁵⁰ focused on treatment of the nasolabial folds and the potential risk for dyspigmentation and keloidal scarring. Taylor et al⁴⁹ noted that the risk of hyperpigmentation was 6% to 9% for large- and small-particle HA, respectively, and was associated with the serial or multiple puncture injection technique. No hypertrophic or keloidal scarring occurred in both studies.^49,50

Facial contouring applications with fillers include glabellar lines, temples, nasal bridge, tear troughs, malar and submalar areas, nasolabial folds, radial lines, lips, marionette lines, mental crease, and chin. Hyaluronic acid fillers also can be used for lip enhancement.⁴⁷ Although white women are looking to increase the size of their lips, black women are seeking augmentation to restore their lip size to that of their youth. Black individuals do not experience the same frequency of perioral rhytides as white patients, but they experience a variety of other issues related to skin sagging and sinking. Unlike white women, enhancement of the vermilion border rarely is performed in black women due to development of rhytides, predominantly in the body of the lip below the vermilion border in response to volume loss in the upper lip while the lower lip usually maintains its same appearance.⁴⁷

Facial enhancement utilizing poly-L-lactic acid can be used safely in SOC patients.⁵¹ Poly-L-lactic acid microparticles induce collagen formation, leading to dermal thickening over 3 to 6 months; however, multiple sessions are required to achieve optimal aesthetic results.

Patients with more reactive collagen can benefit from noninvasive cosmetic procedures such as skin-tightening procedures.⁵² Radiofrequency and microfocused ultrasound are cosmetic procedures used to provide skin tightening and facial lifting. They are safe and effective treatments for patients with Fitzpatrick skin types IV to VI.⁵³ Histologically, there is less thinning of collagen bundles and elastic tissue in ethnic skin. Due to stimulation of collagen by these procedures, most SOC patients will experience a more enhanced response, requiring fewer treatment sessions than white individuals.

Conclusion

Medical and aesthetic facial concerns in SOC patients vary and can be a source of emotional and psychological distress that can negatively impact quality of life. The approach to the treatment of SOC patients should be a balance between tolerability and efficacy, considering the potential risk for PIH.

The approach to the treatment of common skin disorders and cosmetic concerns in patients with skin of color (SOC) requires the clinician to understand the biological differences, nuances, and special considerations that are unique to patients with darker skin types.^1-3 This article addresses 4 common facial concerns in SOC patients—acne, rosacea, facial hyperpigmentation, and cosmetic enhancement—and provides treatment recommendations and management pearls to assist the clinician with optimal outcomes for SOC patients.

Acne in SOC Patients

Acne vulgaris is one of the most common conditions that dermatologists treat and is estimated to affect 40 to 50 million individuals in the United States.¹ Many of these acne patients are individuals with SOC.^2-4 A study of 2835 females (aged 10–70 years) conducted in 4 different cities—Los Angeles, California; London, United Kingdom; Akita, Japan; and Rome, Italy—demonstrated acne prevalence of 37% in blacks, 32% in Hispanics, 30% in Asians, 24% in whites, and 23% in Continental Indians.⁵ Blacks, Hispanics, and Continental Indians demonstrated equal prevalence with comedonal and inflammatory acne. Asians displayed more inflammatory acne lesions than comedones. In contrast, whites demonstrated more comedones than inflammatory acne. Dyspigmentation, postinflammatory hyperpigmentation (PIH), and atrophic scars were more common in black and Hispanic females than other ethnicities.⁵ This study illustrated that acne-induced PIH is a common sequela in SOC patients and is the main reason they seek treatment.^6,7

The pathogenesis of acne is the same in all racial and ethnic groups: (1) follicular hyperkeratinization and the formation of a microcomedone caused by abnormal desquamation of the keratinocytes within the sebaceous follicle, (2) production of sebum by circulating androgens, (3) proliferation of Propionibacterium acnes, and (4) inflammation. Subclinical inflammation is present throughout all stages of acne, including normal-appearing skin, inflammatory lesions, comedones, and scarring, and may contribute to PIH in acne patients with SOC (Figure 1).⁸ A thorough history should be obtained from acne patients, including answers to the following questions⁷:

• What skin and hair care products do you use?
• Do you use sunscreen daily?
• What cosmetic products or makeup do you use?
• Do you use any ethnic skin care products, including skin lightening creams?
• Do you have a history of keloids?

It is important to ask these questions to assess if the SOC patient has developed pomade acne,⁹ acne cosmetica,¹⁰ or a potential risk of skin irritation from the use of skin care practices. It is best to take total control of the patient’s skin care regimen and discontinue use of toners, astringents, witch hazel, exfoliants, and rubbing alcohol, which may lead to skin dryness and irritation, particularly when combined with topical acne medications.

Treatment
Treatment of acne in SOC patients is similar to generally recommended treatments, with special considerations. Consider the following key points when treating acne in SOC patients:

• Treat acne early and aggressively to prevent or minimize subsequent PIH and acne scarring.
• Balance aggressive treatment with nonirritating topical skin care.
• Most importantly, target PIH in addition to acne and choose a regimen that limits skin irritation that might exacerbate existing PIH.⁷

Develop a maintenance program to control future breakouts. Topical agents can be used as monotherapy or in fixed combinations and may include benzoyl peroxide, antibiotics, dapsone, azelaic acid (AZA), and retinoids. Similar to white patients, topical retinoids remain a first-line treatment for acne in patients with SOC.^11,12

Tolerability must be managed in SOC acne patients. Therapeutic maneuvers that can be instituted should include a discussion on using gentle skin care, initiating therapy with a retinoid applied every other night starting with a low concentration and gradually titrating up, and applying a moisturizer before or after applying acne medication. Oral therapies consist of antibiotics (doxycycline, minocycline), retinoids (isotretinoin), and hormonal modulators (oral contraceptives, spironolactone). Isotretinoin, recommended for patients with nodulocystic acne, may play a possible role in treating acne-induced PIH.¹³

Two common procedural therapies for acne include comedone extraction and intralesional corticosteroid injection. A 6- to 8-week course of a topical retinoid prior to comedonal extraction may facilitate the procedure and is recommended in SOC patients to help reduce cutaneous trauma and PIH.¹¹ Inflammatory acne lesions can be treated with intralesional injection of triamcinolone acetonide 2.5 or 5.0 mg/mL, which usually reduces inflammation within 2 to 5 days.¹¹

Treatment of acne-induced PIH includes sun protection, topical and oral medications, chemical peels, lasers, and energy devices. Treatment of hypertrophic scarring and keloids involves intralesional injection of triamcinolone acetonide 20, 30, or 40 mg/mL every 4 weeks until the lesion is flat.¹¹

Superficial chemical peels can be used to treat acne and PIH in SOC patients,¹⁴ such as salicylic acid (20%–30%), glycolic acid (20%–70%), trichloroacetic acid (15%–30%), and Jessner peels.

Acne Scarring
Surgical approaches to acne scarring in patients with SOC include elliptical excision, punch excision, punch elevation, punch autografting, dermal grafting, dermal planning, subcutaneous incision (subcision), dermabrasion, microneedling, fillers, and laser skin resurfacing. The treatment of choice depends on the size, type, and depth of the scar and the clinician’s preference.

Lasers
Fractional photothermolysis has emerged as a treatment option for acne scars in SOC patients. This procedure produces microscopic columns of thermal injury in the epidermis and dermis, sparing the surrounding tissue and minimizing downtime and adverse events. Because fractional photothermolysis does not target melanin and produces limited epidermal injury, darker Fitzpatrick skin types (IV–VI) can be safely and effectively treated with this procedure.¹⁵

Rosacea in SOC Patients

Rosacea is a chronic inflammatory disorder that affects the vasculature and pilosebaceous units of the face. It commonly is seen in Fitzpatrick skin types I and II; however, rosacea can occur in all skin types (Figure 2). Triggers include emotional stress, extreme environmental temperatures, hot and spicy foods, red wine or alcohol, and topical irritants or allergens found in common cosmetic products.¹⁶

Data suggest that 4% of rosacea patients in the United States are of African, Latino, or Asian descent.¹¹ National Ambulatory Medical Care Survey data revealed that of 31.5 million rosacea visits, 2% of patients were black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino. In a 5-year longitudinal study of 2587 rosacea patients enrolled in Medicaid in North Carolina who were prescribed at least 1 topical treatment for rosacea, 16.27% were black and 10% were of a race other than white.¹⁷

Although the pathogenesis of rosacea is unclear, hypotheses include immune system abnormalities, neurogenic dysregulation, presence of microorganisms (eg, Demodex folliculorum), UV damage, and skin barrier dysfunction.¹⁸

The 4 major subtypes of rosacea are erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea.¹⁶ Interestingly, rosacea in SOC patients may present with hypopigmentation surrounding the borders of the facial erythema. For phymatous rosacea, isotretinoin may reduce incipient rhinophyma but must be carefully monitored and pregnancy must be excluded. Surgical or laser therapy may be indicated to recontour the nose if severe.

There are several skin conditions that can present with facial erythema in patients with SOC, including seborrheic dermatitis, systemic lupus erythematosus, and contact dermatitis. It is important to note that the detection of facial erythema in darker skin types may be difficult; therefore, laboratory evaluation (antinuclear antibodies), patch testing, and skin biopsy should be considered if the clinical diagnosis is unclear.

Treatment
Treatment of rosacea in SOC patients does not differ from other racial groups. Common strategies include gentle skin care, sun protection (sun protection factor 30+), and barrier repair creams. Topical agents include metronidazole, AZA, sodium sulfacetamide/sulfur, ivermectin, and retinoids.¹⁶ Oral treatments include antibiotics in the tetracycline family (eg, subantimicrobial dose doxycycline) and isotretinoin.¹⁶ Persistent erythema associated with rosacea can be treated with brimonidine¹⁹ and oxymetazoline.²⁰ Vascular lasers and intense pulsed light may be used to address the vascular components of rosacea²¹; however, the latter is not recommended in Fitzpatrick skin types IV through VI.

Facial Hyperpigmentation in SOC Patients

Hyperpigmentation disorders can be divided into conditions that affect Fitzpatrick skin types I through III and IV though VI. Mottled hyperpigmentation (photodamage) and solar lentigines occur in patients with lighter skin types as compared to melasma, PIH, and age-related (UV-induced) hyperpigmentation, which occur more commonly in patients with darker skin types. Facial hyperpigmentation is a common concern in SOC patients. In a survey of cosmetic concerns of 100 women with SOC, hyperpigmentation or dark spots (86%) and blotchy uneven skin (80%) were the top concerns.²² In addition, facial hyperpigmentation has been shown to negatively impact quality of life.²³

Postinflammatory hyperpigmentation occurs from a pathophysiological response to inflammation, cutaneous irritation or injury, and subsequent melanocyte lability. Postinflammatory hyperpigmentation is a common presenting concern in patients with SOC and is seen as a result of many inflammatory skin disorders (eg, acne, eczema) and dermatologic procedures (eg, adverse reaction to electrodesiccation, microdermabrasion, chemical peels, laser surgery).²⁴

Melasma is an acquired idiopathic disorder of hyperpigmentation and often referred to as the mask of pregnancy (Figure 3). It occurs on sun-exposed areas of skin, mainly in women with Fitzpatrick skin types III through V. Associated factors or triggers include pregnancy, hormonal treatments, exposure to UV radiation, and medications.²⁵ Hereditary factors play a role in more than 40% of cases.²⁶

Other not-so-common facial dyschromias include contact dermatitis, acanthosis nigricans, exogenous ochronosis, lichen planus pigmentosus (associated with frontal fibrosing alopecia),²⁷ drug-induced hyperpigmentation (associated with minocycline or diltiazem),^28,29 and UV-induced (age-related) hyperpigmentation.

Treatment
The treatment of hyperpigmentation should provide the following: (1) protection from sun exposure; (2) inhibition of tyrosinase, the enzyme responsible for the conversion of tyrosine to melanin; (3) inhibition of melanosome transfer from the melanocyte to the keratinocyte; (4) removal of melanin from the epidermis through exfoliation; and (5) destruction or disruption of melanin in the dermis.³⁰ Therapies for facial hyperpigmentation are listed in Table 1.

Topical therapies include prescription medications and nonprescription cosmeceuticals. Prescription medications include hydroquinone (HQ), topical retinoids, and AZA. Hydroquinone, a tyrosinase inhibitor, is the gold standard for skin lightening and often is used as a first-line therapy. It is used as a monotherapy (HQ 4%) or as a fixed combination with tretinoin 0.05% and fluocinolone 0.01%.³¹ Use caution with HQ in high concentrations (6% and higher) and low concentrations (2% [over-the-counter strength]) used long-term due to the potential risk of exogenous ochronosis.

Topical retinoids have been shown to be effective therapeutic agents for melasma and PIH. Tretinoin,³² tazarotene,³³ and adapalene³⁴ all have demonstrated efficacy for acne and acne-induced PIH in SOC patients. Patients must be monitored for the development of retinoid dermatitis and worsening of hyperpigmentation.

Azelaic acid is a naturally occurring dicarboxylic acid obtained from cultures of Malassezia furfur. Azelaic acid inhibits tyrosinase activity, DNA synthesis, and mitochondrial enzymes, thus blocking direct cytotoxic effects toward melanocytes. Azelaic acid is approved by the US Food and Drug Administration for acne in a 20% cream formulation and rosacea in 15% gel and foam formulations, and it is used off label for melasma and PIH.³⁵

Oral tranexamic acid is currently used as a hemostatic agent due to its ability to inhibit the plasminogen-plasmin pathway. In melasma, it blocks the interaction between melanocytes and keratinocytes in the epidermis and modulates the vascular component of melasma in the dermis. In an open-label study, 561 Asian melasma patients were treated with oral tranexamic acid 250 mg twice daily for 4 months. Results demonstrated improvement in 90% of patients, and 7.1% reported adverse effects (eg, abdominal bloating and pain, nausea, vomiting, headache, tinnitus, numbness, menstrual irregularities).³⁶ Coagulation screening should be monitored monthly, and any patient with a history of clotting abnormalities should be excluded from off-label treatment with oral tranexamic acid.

Nonprescription cosmeceuticals are available over-the-counter or are office dispensed.³⁷ For optimal results, cosmeceutical agents for skin lightening are used in combination. Most of these combinations are HQ free and have additive benefits such as a multimodal skin lightening agent containing key ingredients that correct and prevent skin pigmentation via several pathways affecting melanogenesis.³⁸ It is an excellent alternative to HQ for mottled and diffuse UV-induced hyperpigmentation and can be used for maintenance therapy in patients with melasma.

Photoprotection is an essential component of therapy for melasma and PIH, but there is a paucity of data on the benefits for SOC patients. Halder et al³⁹ performed a randomized prospective study of 89 black and Hispanic patients who applied sunscreen with a sun protection factor of 30 or 60 daily for 8 weeks. Clinical grading, triplicate L*A*B chromameter, and clinical photography were taken at baseline and weeks 4 and 8. The results demonstrated skin lightening in both black and Hispanic patients and support the use of sunscreen in the prevention and management of dyschromia in SOC patients.³⁹ Visible light also may play a role in melasma development, and thus use of sunscreens or makeup containing iron oxides are recommended.⁴⁰

Procedural treatments for facial hyperpigmentation include microdermabrasion, chemical peels, lasers, energy-based devices, and microneedling. There are many types and formulations of chemical peeling agents available; however, superficial and medium-depth chemical peels are recommended for SOC patients (Table 2). Deep chemical peels are not recommended for SOC patients due to the potential increased risk for PIH and scarring.

Cosmetic Enhancement in SOC Patients

Cosmetic procedures are gaining popularity in the SOC population and account for more than 20% of cosmetic procedures in the United States.⁴¹ Facial cosmetic concerns in SOC include dyschromia, benign growths (dermatosis papulosa nigra), hyperkinetic facial lines, volume loss, and skin laxity.⁴² Key principles to consider when treating SOC patients are the impact of ethnicity on aging and facial structure, the patient’s desired cosmetic outcome, tissue reaction to anticipated treatments, and the patient’s expectations for recommended therapies.

Aging in SOC Patients
Skin aging can be classified as intrinsic aging or extrinsic aging. Intrinsic aging is genetic and involves subsurface changes such as volume loss, muscle atrophy, and resorption of bony structure. Extrinsic aging (or photoaging) involves surface changes of the epidermis/dermis and manifests as mottled pigmentation, textural changes, and fine wrinkling. Due to the photoprotection of melanin (black skin=SPF 13.4), skin aging in SOC patients is delayed by 10 to 20 years.⁴³ In addition, SOC patients have more reactive collagen and can benefit from noninvasive cosmetic procedures such as fillers and skin-tightening procedures.⁴²

Cosmetic Treatments and Procedures
Dermatosis papulosa nigra (benign growths of skin that have a genetic predisposition)⁴⁴ occur mainly on the face but can involve the entire body. Treatment modalities include electrodesiccation, cryotherapy, scissor excision, and laser surgery.⁴⁵

Treatment of hyperkinetic facial lines with botulinum toxin type A is a safe and effective procedure in patients with SOC. Grimes and Shabazz⁴⁶ performed a 4-month, randomized, double-blind study that evaluated the treatment of glabellar lines in women with Fitzpatrick skin types V and VI. The results demonstrated that the duration of effects was the same in the patients who received either 20 or 30 U of botulinum toxin type A.⁴⁶ Dynamic rhytides (furrows and frown/scowl lines arising from laughing, frowning, or smiling) can be treated safely in patients with SOC using botulinum toxin type A off label for relaxation of the upper and lower hyperkinetic muscles that result in these unwanted signs of aging. Botulinum toxin type A often is used for etched-in crow’s-feet, which rarely are evident in SOC patients.⁴⁷ Facial shaping also can be accomplished by injecting botulinum toxin type A in combination with soft-tissue dermal fillers.⁴⁷

Although black individuals do not experience perioral rhytides at the frequency of white individuals, they experience a variety of other cosmetic issues related to skin sagging and sinking. Currently available hyaluronic acid (HA) fillers have been shown to be safe in patients with Fitzpatrick skin types IV through VI.⁴⁸ Two studies evaluated fillers in patients with SOC, specifically HA⁴⁹ and calcium hydroxylapatite,⁵⁰ focused on treatment of the nasolabial folds and the potential risk for dyspigmentation and keloidal scarring. Taylor et al⁴⁹ noted that the risk of hyperpigmentation was 6% to 9% for large- and small-particle HA, respectively, and was associated with the serial or multiple puncture injection technique. No hypertrophic or keloidal scarring occurred in both studies.^49,50

Facial contouring applications with fillers include glabellar lines, temples, nasal bridge, tear troughs, malar and submalar areas, nasolabial folds, radial lines, lips, marionette lines, mental crease, and chin. Hyaluronic acid fillers also can be used for lip enhancement.⁴⁷ Although white women are looking to increase the size of their lips, black women are seeking augmentation to restore their lip size to that of their youth. Black individuals do not experience the same frequency of perioral rhytides as white patients, but they experience a variety of other issues related to skin sagging and sinking. Unlike white women, enhancement of the vermilion border rarely is performed in black women due to development of rhytides, predominantly in the body of the lip below the vermilion border in response to volume loss in the upper lip while the lower lip usually maintains its same appearance.⁴⁷

Facial enhancement utilizing poly-L-lactic acid can be used safely in SOC patients.⁵¹ Poly-L-lactic acid microparticles induce collagen formation, leading to dermal thickening over 3 to 6 months; however, multiple sessions are required to achieve optimal aesthetic results.

Patients with more reactive collagen can benefit from noninvasive cosmetic procedures such as skin-tightening procedures.⁵² Radiofrequency and microfocused ultrasound are cosmetic procedures used to provide skin tightening and facial lifting. They are safe and effective treatments for patients with Fitzpatrick skin types IV to VI.⁵³ Histologically, there is less thinning of collagen bundles and elastic tissue in ethnic skin. Due to stimulation of collagen by these procedures, most SOC patients will experience a more enhanced response, requiring fewer treatment sessions than white individuals.

Conclusion

Medical and aesthetic facial concerns in SOC patients vary and can be a source of emotional and psychological distress that can negatively impact quality of life. The approach to the treatment of SOC patients should be a balance between tolerability and efficacy, considering the potential risk for PIH.

The approach to the treatment of common skin disorders and cosmetic concerns in patients with skin of color (SOC) requires the clinician to understand the biological differences, nuances, and special considerations that are unique to patients with darker skin types.^1-3 This article addresses 4 common facial concerns in SOC patients—acne, rosacea, facial hyperpigmentation, and cosmetic enhancement—and provides treatment recommendations and management pearls to assist the clinician with optimal outcomes for SOC patients.

Acne in SOC Patients

Acne vulgaris is one of the most common conditions that dermatologists treat and is estimated to affect 40 to 50 million individuals in the United States.¹ Many of these acne patients are individuals with SOC.^2-4 A study of 2835 females (aged 10–70 years) conducted in 4 different cities—Los Angeles, California; London, United Kingdom; Akita, Japan; and Rome, Italy—demonstrated acne prevalence of 37% in blacks, 32% in Hispanics, 30% in Asians, 24% in whites, and 23% in Continental Indians.⁵ Blacks, Hispanics, and Continental Indians demonstrated equal prevalence with comedonal and inflammatory acne. Asians displayed more inflammatory acne lesions than comedones. In contrast, whites demonstrated more comedones than inflammatory acne. Dyspigmentation, postinflammatory hyperpigmentation (PIH), and atrophic scars were more common in black and Hispanic females than other ethnicities.⁵ This study illustrated that acne-induced PIH is a common sequela in SOC patients and is the main reason they seek treatment.^6,7

The pathogenesis of acne is the same in all racial and ethnic groups: (1) follicular hyperkeratinization and the formation of a microcomedone caused by abnormal desquamation of the keratinocytes within the sebaceous follicle, (2) production of sebum by circulating androgens, (3) proliferation of Propionibacterium acnes, and (4) inflammation. Subclinical inflammation is present throughout all stages of acne, including normal-appearing skin, inflammatory lesions, comedones, and scarring, and may contribute to PIH in acne patients with SOC (Figure 1).⁸ A thorough history should be obtained from acne patients, including answers to the following questions⁷:

• What skin and hair care products do you use?
• Do you use sunscreen daily?
• What cosmetic products or makeup do you use?
• Do you use any ethnic skin care products, including skin lightening creams?
• Do you have a history of keloids?

It is important to ask these questions to assess if the SOC patient has developed pomade acne,⁹ acne cosmetica,¹⁰ or a potential risk of skin irritation from the use of skin care practices. It is best to take total control of the patient’s skin care regimen and discontinue use of toners, astringents, witch hazel, exfoliants, and rubbing alcohol, which may lead to skin dryness and irritation, particularly when combined with topical acne medications.

Treatment
Treatment of acne in SOC patients is similar to generally recommended treatments, with special considerations. Consider the following key points when treating acne in SOC patients:

• Treat acne early and aggressively to prevent or minimize subsequent PIH and acne scarring.
• Balance aggressive treatment with nonirritating topical skin care.
• Most importantly, target PIH in addition to acne and choose a regimen that limits skin irritation that might exacerbate existing PIH.⁷

Develop a maintenance program to control future breakouts. Topical agents can be used as monotherapy or in fixed combinations and may include benzoyl peroxide, antibiotics, dapsone, azelaic acid (AZA), and retinoids. Similar to white patients, topical retinoids remain a first-line treatment for acne in patients with SOC.^11,12

Tolerability must be managed in SOC acne patients. Therapeutic maneuvers that can be instituted should include a discussion on using gentle skin care, initiating therapy with a retinoid applied every other night starting with a low concentration and gradually titrating up, and applying a moisturizer before or after applying acne medication. Oral therapies consist of antibiotics (doxycycline, minocycline), retinoids (isotretinoin), and hormonal modulators (oral contraceptives, spironolactone). Isotretinoin, recommended for patients with nodulocystic acne, may play a possible role in treating acne-induced PIH.¹³

Two common procedural therapies for acne include comedone extraction and intralesional corticosteroid injection. A 6- to 8-week course of a topical retinoid prior to comedonal extraction may facilitate the procedure and is recommended in SOC patients to help reduce cutaneous trauma and PIH.¹¹ Inflammatory acne lesions can be treated with intralesional injection of triamcinolone acetonide 2.5 or 5.0 mg/mL, which usually reduces inflammation within 2 to 5 days.¹¹

Treatment of acne-induced PIH includes sun protection, topical and oral medications, chemical peels, lasers, and energy devices. Treatment of hypertrophic scarring and keloids involves intralesional injection of triamcinolone acetonide 20, 30, or 40 mg/mL every 4 weeks until the lesion is flat.¹¹

Superficial chemical peels can be used to treat acne and PIH in SOC patients,¹⁴ such as salicylic acid (20%–30%), glycolic acid (20%–70%), trichloroacetic acid (15%–30%), and Jessner peels.

Acne Scarring
Surgical approaches to acne scarring in patients with SOC include elliptical excision, punch excision, punch elevation, punch autografting, dermal grafting, dermal planning, subcutaneous incision (subcision), dermabrasion, microneedling, fillers, and laser skin resurfacing. The treatment of choice depends on the size, type, and depth of the scar and the clinician’s preference.

Lasers
Fractional photothermolysis has emerged as a treatment option for acne scars in SOC patients. This procedure produces microscopic columns of thermal injury in the epidermis and dermis, sparing the surrounding tissue and minimizing downtime and adverse events. Because fractional photothermolysis does not target melanin and produces limited epidermal injury, darker Fitzpatrick skin types (IV–VI) can be safely and effectively treated with this procedure.¹⁵

Rosacea in SOC Patients

Rosacea is a chronic inflammatory disorder that affects the vasculature and pilosebaceous units of the face. It commonly is seen in Fitzpatrick skin types I and II; however, rosacea can occur in all skin types (Figure 2). Triggers include emotional stress, extreme environmental temperatures, hot and spicy foods, red wine or alcohol, and topical irritants or allergens found in common cosmetic products.¹⁶

Data suggest that 4% of rosacea patients in the United States are of African, Latino, or Asian descent.¹¹ National Ambulatory Medical Care Survey data revealed that of 31.5 million rosacea visits, 2% of patients were black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino. In a 5-year longitudinal study of 2587 rosacea patients enrolled in Medicaid in North Carolina who were prescribed at least 1 topical treatment for rosacea, 16.27% were black and 10% were of a race other than white.¹⁷

Although the pathogenesis of rosacea is unclear, hypotheses include immune system abnormalities, neurogenic dysregulation, presence of microorganisms (eg, Demodex folliculorum), UV damage, and skin barrier dysfunction.¹⁸

The 4 major subtypes of rosacea are erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea.¹⁶ Interestingly, rosacea in SOC patients may present with hypopigmentation surrounding the borders of the facial erythema. For phymatous rosacea, isotretinoin may reduce incipient rhinophyma but must be carefully monitored and pregnancy must be excluded. Surgical or laser therapy may be indicated to recontour the nose if severe.

There are several skin conditions that can present with facial erythema in patients with SOC, including seborrheic dermatitis, systemic lupus erythematosus, and contact dermatitis. It is important to note that the detection of facial erythema in darker skin types may be difficult; therefore, laboratory evaluation (antinuclear antibodies), patch testing, and skin biopsy should be considered if the clinical diagnosis is unclear.

Treatment
Treatment of rosacea in SOC patients does not differ from other racial groups. Common strategies include gentle skin care, sun protection (sun protection factor 30+), and barrier repair creams. Topical agents include metronidazole, AZA, sodium sulfacetamide/sulfur, ivermectin, and retinoids.¹⁶ Oral treatments include antibiotics in the tetracycline family (eg, subantimicrobial dose doxycycline) and isotretinoin.¹⁶ Persistent erythema associated with rosacea can be treated with brimonidine¹⁹ and oxymetazoline.²⁰ Vascular lasers and intense pulsed light may be used to address the vascular components of rosacea²¹; however, the latter is not recommended in Fitzpatrick skin types IV through VI.

Facial Hyperpigmentation in SOC Patients

Hyperpigmentation disorders can be divided into conditions that affect Fitzpatrick skin types I through III and IV though VI. Mottled hyperpigmentation (photodamage) and solar lentigines occur in patients with lighter skin types as compared to melasma, PIH, and age-related (UV-induced) hyperpigmentation, which occur more commonly in patients with darker skin types. Facial hyperpigmentation is a common concern in SOC patients. In a survey of cosmetic concerns of 100 women with SOC, hyperpigmentation or dark spots (86%) and blotchy uneven skin (80%) were the top concerns.²² In addition, facial hyperpigmentation has been shown to negatively impact quality of life.²³

Postinflammatory hyperpigmentation occurs from a pathophysiological response to inflammation, cutaneous irritation or injury, and subsequent melanocyte lability. Postinflammatory hyperpigmentation is a common presenting concern in patients with SOC and is seen as a result of many inflammatory skin disorders (eg, acne, eczema) and dermatologic procedures (eg, adverse reaction to electrodesiccation, microdermabrasion, chemical peels, laser surgery).²⁴

Melasma is an acquired idiopathic disorder of hyperpigmentation and often referred to as the mask of pregnancy (Figure 3). It occurs on sun-exposed areas of skin, mainly in women with Fitzpatrick skin types III through V. Associated factors or triggers include pregnancy, hormonal treatments, exposure to UV radiation, and medications.²⁵ Hereditary factors play a role in more than 40% of cases.²⁶

Other not-so-common facial dyschromias include contact dermatitis, acanthosis nigricans, exogenous ochronosis, lichen planus pigmentosus (associated with frontal fibrosing alopecia),²⁷ drug-induced hyperpigmentation (associated with minocycline or diltiazem),^28,29 and UV-induced (age-related) hyperpigmentation.

Treatment
The treatment of hyperpigmentation should provide the following: (1) protection from sun exposure; (2) inhibition of tyrosinase, the enzyme responsible for the conversion of tyrosine to melanin; (3) inhibition of melanosome transfer from the melanocyte to the keratinocyte; (4) removal of melanin from the epidermis through exfoliation; and (5) destruction or disruption of melanin in the dermis.³⁰ Therapies for facial hyperpigmentation are listed in Table 1.

Topical therapies include prescription medications and nonprescription cosmeceuticals. Prescription medications include hydroquinone (HQ), topical retinoids, and AZA. Hydroquinone, a tyrosinase inhibitor, is the gold standard for skin lightening and often is used as a first-line therapy. It is used as a monotherapy (HQ 4%) or as a fixed combination with tretinoin 0.05% and fluocinolone 0.01%.³¹ Use caution with HQ in high concentrations (6% and higher) and low concentrations (2% [over-the-counter strength]) used long-term due to the potential risk of exogenous ochronosis.

Topical retinoids have been shown to be effective therapeutic agents for melasma and PIH. Tretinoin,³² tazarotene,³³ and adapalene³⁴ all have demonstrated efficacy for acne and acne-induced PIH in SOC patients. Patients must be monitored for the development of retinoid dermatitis and worsening of hyperpigmentation.

Azelaic acid is a naturally occurring dicarboxylic acid obtained from cultures of Malassezia furfur. Azelaic acid inhibits tyrosinase activity, DNA synthesis, and mitochondrial enzymes, thus blocking direct cytotoxic effects toward melanocytes. Azelaic acid is approved by the US Food and Drug Administration for acne in a 20% cream formulation and rosacea in 15% gel and foam formulations, and it is used off label for melasma and PIH.³⁵

Oral tranexamic acid is currently used as a hemostatic agent due to its ability to inhibit the plasminogen-plasmin pathway. In melasma, it blocks the interaction between melanocytes and keratinocytes in the epidermis and modulates the vascular component of melasma in the dermis. In an open-label study, 561 Asian melasma patients were treated with oral tranexamic acid 250 mg twice daily for 4 months. Results demonstrated improvement in 90% of patients, and 7.1% reported adverse effects (eg, abdominal bloating and pain, nausea, vomiting, headache, tinnitus, numbness, menstrual irregularities).³⁶ Coagulation screening should be monitored monthly, and any patient with a history of clotting abnormalities should be excluded from off-label treatment with oral tranexamic acid.

Nonprescription cosmeceuticals are available over-the-counter or are office dispensed.³⁷ For optimal results, cosmeceutical agents for skin lightening are used in combination. Most of these combinations are HQ free and have additive benefits such as a multimodal skin lightening agent containing key ingredients that correct and prevent skin pigmentation via several pathways affecting melanogenesis.³⁸ It is an excellent alternative to HQ for mottled and diffuse UV-induced hyperpigmentation and can be used for maintenance therapy in patients with melasma.

Photoprotection is an essential component of therapy for melasma and PIH, but there is a paucity of data on the benefits for SOC patients. Halder et al³⁹ performed a randomized prospective study of 89 black and Hispanic patients who applied sunscreen with a sun protection factor of 30 or 60 daily for 8 weeks. Clinical grading, triplicate L*A*B chromameter, and clinical photography were taken at baseline and weeks 4 and 8. The results demonstrated skin lightening in both black and Hispanic patients and support the use of sunscreen in the prevention and management of dyschromia in SOC patients.³⁹ Visible light also may play a role in melasma development, and thus use of sunscreens or makeup containing iron oxides are recommended.⁴⁰

Procedural treatments for facial hyperpigmentation include microdermabrasion, chemical peels, lasers, energy-based devices, and microneedling. There are many types and formulations of chemical peeling agents available; however, superficial and medium-depth chemical peels are recommended for SOC patients (Table 2). Deep chemical peels are not recommended for SOC patients due to the potential increased risk for PIH and scarring.

Cosmetic Enhancement in SOC Patients

Cosmetic procedures are gaining popularity in the SOC population and account for more than 20% of cosmetic procedures in the United States.⁴¹ Facial cosmetic concerns in SOC include dyschromia, benign growths (dermatosis papulosa nigra), hyperkinetic facial lines, volume loss, and skin laxity.⁴² Key principles to consider when treating SOC patients are the impact of ethnicity on aging and facial structure, the patient’s desired cosmetic outcome, tissue reaction to anticipated treatments, and the patient’s expectations for recommended therapies.

Aging in SOC Patients
Skin aging can be classified as intrinsic aging or extrinsic aging. Intrinsic aging is genetic and involves subsurface changes such as volume loss, muscle atrophy, and resorption of bony structure. Extrinsic aging (or photoaging) involves surface changes of the epidermis/dermis and manifests as mottled pigmentation, textural changes, and fine wrinkling. Due to the photoprotection of melanin (black skin=SPF 13.4), skin aging in SOC patients is delayed by 10 to 20 years.⁴³ In addition, SOC patients have more reactive collagen and can benefit from noninvasive cosmetic procedures such as fillers and skin-tightening procedures.⁴²

Cosmetic Treatments and Procedures
Dermatosis papulosa nigra (benign growths of skin that have a genetic predisposition)⁴⁴ occur mainly on the face but can involve the entire body. Treatment modalities include electrodesiccation, cryotherapy, scissor excision, and laser surgery.⁴⁵

Treatment of hyperkinetic facial lines with botulinum toxin type A is a safe and effective procedure in patients with SOC. Grimes and Shabazz⁴⁶ performed a 4-month, randomized, double-blind study that evaluated the treatment of glabellar lines in women with Fitzpatrick skin types V and VI. The results demonstrated that the duration of effects was the same in the patients who received either 20 or 30 U of botulinum toxin type A.⁴⁶ Dynamic rhytides (furrows and frown/scowl lines arising from laughing, frowning, or smiling) can be treated safely in patients with SOC using botulinum toxin type A off label for relaxation of the upper and lower hyperkinetic muscles that result in these unwanted signs of aging. Botulinum toxin type A often is used for etched-in crow’s-feet, which rarely are evident in SOC patients.⁴⁷ Facial shaping also can be accomplished by injecting botulinum toxin type A in combination with soft-tissue dermal fillers.⁴⁷

Although black individuals do not experience perioral rhytides at the frequency of white individuals, they experience a variety of other cosmetic issues related to skin sagging and sinking. Currently available hyaluronic acid (HA) fillers have been shown to be safe in patients with Fitzpatrick skin types IV through VI.⁴⁸ Two studies evaluated fillers in patients with SOC, specifically HA⁴⁹ and calcium hydroxylapatite,⁵⁰ focused on treatment of the nasolabial folds and the potential risk for dyspigmentation and keloidal scarring. Taylor et al⁴⁹ noted that the risk of hyperpigmentation was 6% to 9% for large- and small-particle HA, respectively, and was associated with the serial or multiple puncture injection technique. No hypertrophic or keloidal scarring occurred in both studies.^49,50

Facial contouring applications with fillers include glabellar lines, temples, nasal bridge, tear troughs, malar and submalar areas, nasolabial folds, radial lines, lips, marionette lines, mental crease, and chin. Hyaluronic acid fillers also can be used for lip enhancement.⁴⁷ Although white women are looking to increase the size of their lips, black women are seeking augmentation to restore their lip size to that of their youth. Black individuals do not experience the same frequency of perioral rhytides as white patients, but they experience a variety of other issues related to skin sagging and sinking. Unlike white women, enhancement of the vermilion border rarely is performed in black women due to development of rhytides, predominantly in the body of the lip below the vermilion border in response to volume loss in the upper lip while the lower lip usually maintains its same appearance.⁴⁷

Facial enhancement utilizing poly-L-lactic acid can be used safely in SOC patients.⁵¹ Poly-L-lactic acid microparticles induce collagen formation, leading to dermal thickening over 3 to 6 months; however, multiple sessions are required to achieve optimal aesthetic results.

Patients with more reactive collagen can benefit from noninvasive cosmetic procedures such as skin-tightening procedures.⁵² Radiofrequency and microfocused ultrasound are cosmetic procedures used to provide skin tightening and facial lifting. They are safe and effective treatments for patients with Fitzpatrick skin types IV to VI.⁵³ Histologically, there is less thinning of collagen bundles and elastic tissue in ethnic skin. Due to stimulation of collagen by these procedures, most SOC patients will experience a more enhanced response, requiring fewer treatment sessions than white individuals.

Conclusion

Medical and aesthetic facial concerns in SOC patients vary and can be a source of emotional and psychological distress that can negatively impact quality of life. The approach to the treatment of SOC patients should be a balance between tolerability and efficacy, considering the potential risk for PIH.

Perioral dermatitis is an acneform eruption presenting with erythematous papules, vesicles, and rarely pustules clustered around the orifices of the face. ¹ Lesions may be found near the eyes, mouth, and nose but typically spare the vermilion border of the lips. ² Nguyen and Eichenfield ³ preferred the term periorificial dermatitis (POD), which has since been adopted by others. ⁴ Patients may report pruritus, but there generally are no systemic symptoms unless patients have comorbid conditions such as atopic dermatitis. ⁵ Although this condition has been well examined in the literature on adults, data in the pediatric population are far more limited, consisting of case series and retrospective chart reviews. In 1979, Wilkinson et al ⁶ published a study of more than 200 patients with perioral dermatitis, but only 15 patients younger than 12 years were included.

Etiology

Although the exact pathogenesis of POD is unknown, a common denominator among many patients is prior exposure to topical corticosteroids.^3,7-9 Periorificial dermatitis also has been linked to the use of systemic corticosteroids in pediatric patients.¹⁰ The exact relationship between steroid use and dermatitis is unknown; it may be related to a change in the flora of hair follicles and in particular an association with fusiform bacteria–rich conditions.¹¹ Aside from steroid exposure, POD has been associated with the use of physical sunscreen in pediatric patients with dry skin,¹² rosin in chewing gum,¹³ and inhaled corticosteroids in those with asthma.¹⁴ In one case, a 15-year-old adolescent girl developed POD and swelling of the lips after 2 years of playing a flute made of cocus wood.^15,16

Epidemiology

In the largest chart review to date in the US pediatric population, Goel et al¹⁷ examined the clinical course of POD in 222 patients aged 3 months to 18 years at the Dermatology Clinic at the University of North Carolina Chapel Hill between June 2002 and March 2014. Consistent with prior studies, females seemed to be slightly more affected than males (55.4% vs 44.6%).¹⁷ Similarly, the patient population for a study conducted by Nguyen and Eichenfield³ consisted of more females (58% [46/79]) than males (42% [33/79]). Weston and Morelli⁹ conducted a retrospective chart review of steroid rosacea in 106 patients younger than 13 years, which included 29 patients younger than 3 years; the study included 46 males and 60 females.

Comorbidities and Family History

Goel et al¹⁷ (N=222) reported the following comorbidities associated with pediatric POD: atopic dermatitis (29.3%), asthma (14.9%), and allergies (9.9%). Steroid exposure was noted in 58.1% of patients.¹⁷ Similarly, Nguyen and Eichenfield³ (N=79) found that the most common comorbidities were atopic dermatitis (14%), keratosis pilaris (14%), viral infections (14%), acne (10%), and seborrheic dermatitis (10%). Family history of atopy was noted in 55% of patients and family history of rosacea was noted in 3%. In a case series of 11 pediatric patients, 3 (27%) had keratosis pilaris, 7 (64%) had a family history of atopy, and 2 (18%) had a family history of rosacea.⁸ Weston and Morelli⁹ found a much higher incidence of familial rosacea (20%) in 106 children with steroid rosacea. It is hard to interpret the role of genetic tendency in rosacea, as different populations have different background prevalence of rosacea and atopic dermatitis (ie, rosacea is immensely more common in white individuals).

Clinical Presentation

Periorificial dermatitis generally presents with small, pink- to flesh-colored papules in a perioral, periocular, and perinasal distribution. Although many patients are white, a particularly prominent variant has been noted in black children with papules that may be hyperpigmented.¹⁸ In a 2006 chart review in 79 pediatric POD patients aged 6 months to 18 years, Nguyen and Eichenfield³ reported that 92% (73/79) of patients presented for a facial rash with an average duration ranging from 2 weeks to 4 years. Interestingly, although Tempark and Shwayder¹ did not report burning associated with pediatric POD, Nguyen and Eichenfield³ found that 19% of patients reported pruritus and 4% reported burning or tenderness. Seventy-two percent of patients had been exposed to steroids for treatment of their dermatitis. Seventy percent had perioral involvement, 43% had perinasal involvement, 25% had periocular involvement, and 1% had a perivulvar rash; 64% of patients only had perioral, perinasal, and periocular involvement. In others, lesions also were found on the cheeks, chin, neck, and forehead. Perioral lesions were more likely to be found in patients younger than 5 years compared to those who were at least 5 years of age. Eighty-six percent of patients had erythema with or without scaling, 66% had papules, and 11% had pustules. Fewer than 3% had lichenification, telangiectases, or changes in pigmentation.³

Boeck et al¹⁹ described 7 pediatric patients with perioral dermatitis. Six (86%) patients had perioral lesions, and 6 (86%) had previously been treated with moderate- to high-potency topical corticosteroids. Skin prick tests were negative in 6 (86%) patients.¹⁹ In one case report, a 6-year-old boy did not present with the classic acneform lesions but rather sharply demarcated eczematous patches around the eyes, nose, and mouth. The rash began to fade after 2 weeks of using metronidazole gel 1%, and after 4 months he was only left with mild hyperpigmentation.⁴

Periorificial dermatitis was once thought to be a juvenile form of rosacea.⁵ In 1972, Savin et al⁸ described 11 pediatric patients with “rosacea-like” facial flushing, papules, pustules, and scaling over the cheeks, forehead, and chin. In some patients, the eyelids also were involved. At least 8 patients had been using potent topical corticosteroids and had noticed exacerbation of their skin lesions after stopping therapy.⁸

Variants of POD

Several other variants of POD have been described in pediatric patients including childhood granulomatous periorificial dermatitis (CGPD)(also known as facial Afro-Caribbean [childhood] eruption) and lupus miliaris disseminatus faciei. Childhood granulomatous periorificial dermatitis presents in prepubertal children as dome-shaped, red to yellow-brown, monomorphous papules around the eyes, nose, and mouth; there are no systemic findings.^20,21 It occurs equally in males and females and is more commonly seen in dark-skinned patients. Childhood granulomatous periorificial dermatitis usually resolves within a few months to years but may be associated with blepharitis or conjunctivitis.²⁰ Urbatsch et al²⁰ analyzed extrafacial lesions in 8 patients (aged 2–12 years) with CGPD. Lesions were found on the trunk (38% [3/8]), neck (25% [2/8]), ears (25% [2/8]), extremities (50% [4/8]), labia majora (38% [3/8]), and abdomen (13% [1/8]). In addition, 2 (25% [2/8]) patients had blepharitis.²⁰

Lupus miliaris disseminatus faciei, which occurs in adolescents and adults, commonly involves the eyelids and central areas of the face such as the nose and upper lips. Patients typically present with erythematous or flesh-colored papules.¹

Diagnosis

Diagnosis of POD is made clinically based on the observation of papules (and sometimes pustules) around the orifices of the face, sparing the vermilion border, together with a lack of comedones.¹⁷ Laboratory tests are not useful.⁵ Biopsies rarely are performed, and the results mimic those of rosacea, demonstrating a perifollicular lymphohistiocytic infiltrate, epithelioid cells, and occasionally giant cells.^5,22,23 Early papular lesions can show mild acanthosis, epidermal edema, and parakeratosis.²³ Biopsies in patients with CGPD reveal noncaseating perifollicular granulomas.²⁰

Treatment and Clinical Outcome

Although topical corticosteroids can improve facial lesions in pediatric POD, the eruption often rebounds when therapy is discontinued.¹ One therapy frequently used in adults is oral tetracyclines; however, these agents must not be used in patients younger than 9 years due to potential dental staining.⁴ The standards are either topical metronidazole twice daily with clearance in 3 to 8 weeks or oral erythromycin.⁷

In the review conducted by Goel et al,¹⁷ treatment included azithromycin (44.6%), topical metronidazole (42.3%), sodium sulfacetamide lotion (35.6%), oral antibiotic monotherapy (15.3%), topical agent monotherapy (44.6%), and combined oral and topical agent therapy (40.1%). Of those patients who presented for a follow-up visit (59%), 72% of cases resolved and 10.7% showed some improvement. For those patients who returned for follow-up, the average duration until symptom resolution was approximately 4 months. The most common side effects were pigmentation changes (1.8%), worsening of symptoms (1.8%), gastrointestinal upset (0.9%), irritant dermatitis (0.9%), and xerosis (0.5%).¹⁷

Changes were made to the treatment plans for 16 patients, most often due to inadequate treatment response.¹⁷ Five patients treated with sodium sulfacetamide lotion also were started on oral azithromycin. Four patients treated with oral antibiotics were given a topical agent (metronidazole or sodium sulfacetamide lotion). Other modifications included replacing sodium sulfacetamide lotion with topical metronidazole and an oral antibiotic (azithromycin or doxycycline, n=3), adjusting the doses of oral or topical medications (n=2), adding tacrolimus (n=1), and replacing topical metronidazole with sodium sulfacetamide lotion (n=1). Of the patients who underwent a change in treatment plan, 5 experienced symptom recurrence, 4 had mild improvement, and 1 patient had no improvement. Six patients were lost to follow-up.¹⁷

In the study conducted by Nguyen and Eichenfield,³ follow-up visits occurred approximately 3 months after the first visit. Fifty-two percent of patients used metronidazole alone or with another medication; for most of these patients, the POD cleared an average of 7 weeks after starting treatment, ranging from 1 to 24 weeks. The use of topical calcineurin inhibitors, sulfacetamide, hydrocortisone, or antifungal therapies was associated with persistence of the rash at the follow-up visit. In contrast, the use of metronidazole and/or oral erythromycin was associated with resolution of the rash at the follow-up visit. The investigators recommended the following regimen: topical metronidazole for 1 to 2 months and, if necessary, the addition of oral erythromycin.³

In the case series by Boeck et al,¹⁹ all patients were started on metronidazole gel 1% applied once daily for the first week, and then twice daily until the lesions resolved. All patients showed improvement after 4 to 6 weeks, and eventually the disease cleared between 3 and 6 months. All patients were still symptom free during a 2-year observation period.¹⁹

Manders and Lucky⁷ described 14 patients with POD (aged 9 months to 6.5 years). Eight patients used only metronidazole gel 0.75%, while 5 used the gel in combination with topical corticosteroids (21% [3/14]), oral erythromycin (7% [1/14]), or topical erythromycin (7% [1/14]); 1 patient remained on hydrocortisone 1% and cleared. Patients responded well within 1 to 8 weeks and were symptom free for up to 16 months. Mid- to high-potency steroids were discontinued in all patients.⁷

In some pediatric patients with CGPD, recovery occurs faster with the use of oral macrolides or tetracyclines, either alone or in combination with topical antibiotics or sulfur-based lotions.²⁰ Extrafacial lesions associated with CGPD do not appear to negatively impact treatment response or duration of disease. In the review conducted by Urbatsch et al,²⁰ 7 of 8 (88%) CGPD patients with extrafacial lesions were treated with oral agents including erythromycin, hydroxychloroquine, cyclosporine, minocycline, and azithromycin. Most of these patients also were using topical agents such as triamcinolone acetonide, desonide, metronidazole, and erythromycin. The time to resolution ranged from several weeks to 6 months.²⁰

Weston and Morelli⁹ described a treatment regimen for steroid rosacea. The study included data on 106 children (60 females, 46 males) who had been exposed to mostly class 7 low-potency agents. All patients were advised to immediately stop topical steroid therapy without gradual withdrawal and to begin oral erythromycin stearate 30 mg/kg daily in 2 doses per day for 4 weeks. Patients who were unable to tolerate erythromycin were advised to use topical clindamycin phosphate twice daily for 4 weeks (n=6). Eighty-six percent of patients showed resolution within 4 weeks, and 100% showed clearance by 8 weeks. Twenty-two percent of patients had clearance within 3 weeks. There was no difference in the duration until resolution for those who had used oral or topical antibiotics.⁹ A different study suggested that low-potency topical steroids can be used to control inflammation when weaning patients off of strong steroids.⁵

Differential Diagnosis

The differential diagnosis should include acne vulgaris, allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis, impetigo, dermatophyte infection, rosacea, and angiofibromas.⁴

Acne vulgaris commonly is found in older adolescents, and unlike POD, it will present with open or closed comedones.² In patients aged 1 to 7 years, acne is a reason to consider endocrine evaluation. Allergic contact dermatitis is extremely pruritic, and the lesions often are papulovesicular with active weeping or crusting. Patients with irritant contact dermatitis often report burning and pain, and papules and pustules typically are absent. A thorough history can help rule out allergic or irritant contact dermatitis. Seborrheic dermatitis presents with erythema and scaling of the scalp, eyebrows, and nasolabial folds; it tends to spare the perioral regions and also lacks papules.² The lesions of impetigo typically have a yellow-brown exudate, which forms a honey-colored crust.²⁴ Tinea faciei, unlike the other tinea infections, can have an extremely variable presentation. Lesions usually begin as scaly macules that develop raised borders with central hypopigmentation, but papules, vesicles, and crusts can be seen.²⁵ Potassium hydroxide preparation can help diagnose a fungal infection. Rosacea presents with flushing of the central face regions, sometimes accompanied by papules, pustules, and telangiectases.² Although rare, physicians must rule out angiofibromas. Typically found in patients older than 5 years, angiofibromas are pink or flesh-colored papules often found on the nasolabial folds, cheeks, and chin.² Many angiofibromas can be associated with tuberous sclerosis.

Conclusion

Diagnosis of POD is clinical and rests upon the finding of erythematous papules on the face near the eyes, mouth, and nose. Extrafacial lesions also have been described, particularly in pediatric patients with CGPD. Many patients will report a history of atopic dermatitis and asthma. Therapy for POD includes both topical and systemic agents. For those with mild disease, topical metronidazole commonly is used. For patients requiring oral antibiotics, tetracyclines or macrolides can be prescribed based on the age of the patient. Many pediatric patients who begin with both oral and topical agents can later be maintained on topical therapy, sometimes with a low-dose oral antibiotic. Periorificial dermatitis has an excellent prognosis and most pediatric patients show marked improvement within weeks to months.

Perioral dermatitis is an acneform eruption presenting with erythematous papules, vesicles, and rarely pustules clustered around the orifices of the face. ¹ Lesions may be found near the eyes, mouth, and nose but typically spare the vermilion border of the lips. ² Nguyen and Eichenfield ³ preferred the term periorificial dermatitis (POD), which has since been adopted by others. ⁴ Patients may report pruritus, but there generally are no systemic symptoms unless patients have comorbid conditions such as atopic dermatitis. ⁵ Although this condition has been well examined in the literature on adults, data in the pediatric population are far more limited, consisting of case series and retrospective chart reviews. In 1979, Wilkinson et al ⁶ published a study of more than 200 patients with perioral dermatitis, but only 15 patients younger than 12 years were included.

Etiology

Although the exact pathogenesis of POD is unknown, a common denominator among many patients is prior exposure to topical corticosteroids.^3,7-9 Periorificial dermatitis also has been linked to the use of systemic corticosteroids in pediatric patients.¹⁰ The exact relationship between steroid use and dermatitis is unknown; it may be related to a change in the flora of hair follicles and in particular an association with fusiform bacteria–rich conditions.¹¹ Aside from steroid exposure, POD has been associated with the use of physical sunscreen in pediatric patients with dry skin,¹² rosin in chewing gum,¹³ and inhaled corticosteroids in those with asthma.¹⁴ In one case, a 15-year-old adolescent girl developed POD and swelling of the lips after 2 years of playing a flute made of cocus wood.^15,16

Epidemiology

In the largest chart review to date in the US pediatric population, Goel et al¹⁷ examined the clinical course of POD in 222 patients aged 3 months to 18 years at the Dermatology Clinic at the University of North Carolina Chapel Hill between June 2002 and March 2014. Consistent with prior studies, females seemed to be slightly more affected than males (55.4% vs 44.6%).¹⁷ Similarly, the patient population for a study conducted by Nguyen and Eichenfield³ consisted of more females (58% [46/79]) than males (42% [33/79]). Weston and Morelli⁹ conducted a retrospective chart review of steroid rosacea in 106 patients younger than 13 years, which included 29 patients younger than 3 years; the study included 46 males and 60 females.

Comorbidities and Family History

Goel et al¹⁷ (N=222) reported the following comorbidities associated with pediatric POD: atopic dermatitis (29.3%), asthma (14.9%), and allergies (9.9%). Steroid exposure was noted in 58.1% of patients.¹⁷ Similarly, Nguyen and Eichenfield³ (N=79) found that the most common comorbidities were atopic dermatitis (14%), keratosis pilaris (14%), viral infections (14%), acne (10%), and seborrheic dermatitis (10%). Family history of atopy was noted in 55% of patients and family history of rosacea was noted in 3%. In a case series of 11 pediatric patients, 3 (27%) had keratosis pilaris, 7 (64%) had a family history of atopy, and 2 (18%) had a family history of rosacea.⁸ Weston and Morelli⁹ found a much higher incidence of familial rosacea (20%) in 106 children with steroid rosacea. It is hard to interpret the role of genetic tendency in rosacea, as different populations have different background prevalence of rosacea and atopic dermatitis (ie, rosacea is immensely more common in white individuals).

Clinical Presentation

Periorificial dermatitis generally presents with small, pink- to flesh-colored papules in a perioral, periocular, and perinasal distribution. Although many patients are white, a particularly prominent variant has been noted in black children with papules that may be hyperpigmented.¹⁸ In a 2006 chart review in 79 pediatric POD patients aged 6 months to 18 years, Nguyen and Eichenfield³ reported that 92% (73/79) of patients presented for a facial rash with an average duration ranging from 2 weeks to 4 years. Interestingly, although Tempark and Shwayder¹ did not report burning associated with pediatric POD, Nguyen and Eichenfield³ found that 19% of patients reported pruritus and 4% reported burning or tenderness. Seventy-two percent of patients had been exposed to steroids for treatment of their dermatitis. Seventy percent had perioral involvement, 43% had perinasal involvement, 25% had periocular involvement, and 1% had a perivulvar rash; 64% of patients only had perioral, perinasal, and periocular involvement. In others, lesions also were found on the cheeks, chin, neck, and forehead. Perioral lesions were more likely to be found in patients younger than 5 years compared to those who were at least 5 years of age. Eighty-six percent of patients had erythema with or without scaling, 66% had papules, and 11% had pustules. Fewer than 3% had lichenification, telangiectases, or changes in pigmentation.³

Boeck et al¹⁹ described 7 pediatric patients with perioral dermatitis. Six (86%) patients had perioral lesions, and 6 (86%) had previously been treated with moderate- to high-potency topical corticosteroids. Skin prick tests were negative in 6 (86%) patients.¹⁹ In one case report, a 6-year-old boy did not present with the classic acneform lesions but rather sharply demarcated eczematous patches around the eyes, nose, and mouth. The rash began to fade after 2 weeks of using metronidazole gel 1%, and after 4 months he was only left with mild hyperpigmentation.⁴

Periorificial dermatitis was once thought to be a juvenile form of rosacea.⁵ In 1972, Savin et al⁸ described 11 pediatric patients with “rosacea-like” facial flushing, papules, pustules, and scaling over the cheeks, forehead, and chin. In some patients, the eyelids also were involved. At least 8 patients had been using potent topical corticosteroids and had noticed exacerbation of their skin lesions after stopping therapy.⁸

Variants of POD

Several other variants of POD have been described in pediatric patients including childhood granulomatous periorificial dermatitis (CGPD)(also known as facial Afro-Caribbean [childhood] eruption) and lupus miliaris disseminatus faciei. Childhood granulomatous periorificial dermatitis presents in prepubertal children as dome-shaped, red to yellow-brown, monomorphous papules around the eyes, nose, and mouth; there are no systemic findings.^20,21 It occurs equally in males and females and is more commonly seen in dark-skinned patients. Childhood granulomatous periorificial dermatitis usually resolves within a few months to years but may be associated with blepharitis or conjunctivitis.²⁰ Urbatsch et al²⁰ analyzed extrafacial lesions in 8 patients (aged 2–12 years) with CGPD. Lesions were found on the trunk (38% [3/8]), neck (25% [2/8]), ears (25% [2/8]), extremities (50% [4/8]), labia majora (38% [3/8]), and abdomen (13% [1/8]). In addition, 2 (25% [2/8]) patients had blepharitis.²⁰

Lupus miliaris disseminatus faciei, which occurs in adolescents and adults, commonly involves the eyelids and central areas of the face such as the nose and upper lips. Patients typically present with erythematous or flesh-colored papules.¹

Diagnosis

Diagnosis of POD is made clinically based on the observation of papules (and sometimes pustules) around the orifices of the face, sparing the vermilion border, together with a lack of comedones.¹⁷ Laboratory tests are not useful.⁵ Biopsies rarely are performed, and the results mimic those of rosacea, demonstrating a perifollicular lymphohistiocytic infiltrate, epithelioid cells, and occasionally giant cells.^5,22,23 Early papular lesions can show mild acanthosis, epidermal edema, and parakeratosis.²³ Biopsies in patients with CGPD reveal noncaseating perifollicular granulomas.²⁰

Treatment and Clinical Outcome

Although topical corticosteroids can improve facial lesions in pediatric POD, the eruption often rebounds when therapy is discontinued.¹ One therapy frequently used in adults is oral tetracyclines; however, these agents must not be used in patients younger than 9 years due to potential dental staining.⁴ The standards are either topical metronidazole twice daily with clearance in 3 to 8 weeks or oral erythromycin.⁷

In the review conducted by Goel et al,¹⁷ treatment included azithromycin (44.6%), topical metronidazole (42.3%), sodium sulfacetamide lotion (35.6%), oral antibiotic monotherapy (15.3%), topical agent monotherapy (44.6%), and combined oral and topical agent therapy (40.1%). Of those patients who presented for a follow-up visit (59%), 72% of cases resolved and 10.7% showed some improvement. For those patients who returned for follow-up, the average duration until symptom resolution was approximately 4 months. The most common side effects were pigmentation changes (1.8%), worsening of symptoms (1.8%), gastrointestinal upset (0.9%), irritant dermatitis (0.9%), and xerosis (0.5%).¹⁷

Changes were made to the treatment plans for 16 patients, most often due to inadequate treatment response.¹⁷ Five patients treated with sodium sulfacetamide lotion also were started on oral azithromycin. Four patients treated with oral antibiotics were given a topical agent (metronidazole or sodium sulfacetamide lotion). Other modifications included replacing sodium sulfacetamide lotion with topical metronidazole and an oral antibiotic (azithromycin or doxycycline, n=3), adjusting the doses of oral or topical medications (n=2), adding tacrolimus (n=1), and replacing topical metronidazole with sodium sulfacetamide lotion (n=1). Of the patients who underwent a change in treatment plan, 5 experienced symptom recurrence, 4 had mild improvement, and 1 patient had no improvement. Six patients were lost to follow-up.¹⁷

In the study conducted by Nguyen and Eichenfield,³ follow-up visits occurred approximately 3 months after the first visit. Fifty-two percent of patients used metronidazole alone or with another medication; for most of these patients, the POD cleared an average of 7 weeks after starting treatment, ranging from 1 to 24 weeks. The use of topical calcineurin inhibitors, sulfacetamide, hydrocortisone, or antifungal therapies was associated with persistence of the rash at the follow-up visit. In contrast, the use of metronidazole and/or oral erythromycin was associated with resolution of the rash at the follow-up visit. The investigators recommended the following regimen: topical metronidazole for 1 to 2 months and, if necessary, the addition of oral erythromycin.³

In the case series by Boeck et al,¹⁹ all patients were started on metronidazole gel 1% applied once daily for the first week, and then twice daily until the lesions resolved. All patients showed improvement after 4 to 6 weeks, and eventually the disease cleared between 3 and 6 months. All patients were still symptom free during a 2-year observation period.¹⁹

Manders and Lucky⁷ described 14 patients with POD (aged 9 months to 6.5 years). Eight patients used only metronidazole gel 0.75%, while 5 used the gel in combination with topical corticosteroids (21% [3/14]), oral erythromycin (7% [1/14]), or topical erythromycin (7% [1/14]); 1 patient remained on hydrocortisone 1% and cleared. Patients responded well within 1 to 8 weeks and were symptom free for up to 16 months. Mid- to high-potency steroids were discontinued in all patients.⁷

In some pediatric patients with CGPD, recovery occurs faster with the use of oral macrolides or tetracyclines, either alone or in combination with topical antibiotics or sulfur-based lotions.²⁰ Extrafacial lesions associated with CGPD do not appear to negatively impact treatment response or duration of disease. In the review conducted by Urbatsch et al,²⁰ 7 of 8 (88%) CGPD patients with extrafacial lesions were treated with oral agents including erythromycin, hydroxychloroquine, cyclosporine, minocycline, and azithromycin. Most of these patients also were using topical agents such as triamcinolone acetonide, desonide, metronidazole, and erythromycin. The time to resolution ranged from several weeks to 6 months.²⁰

Weston and Morelli⁹ described a treatment regimen for steroid rosacea. The study included data on 106 children (60 females, 46 males) who had been exposed to mostly class 7 low-potency agents. All patients were advised to immediately stop topical steroid therapy without gradual withdrawal and to begin oral erythromycin stearate 30 mg/kg daily in 2 doses per day for 4 weeks. Patients who were unable to tolerate erythromycin were advised to use topical clindamycin phosphate twice daily for 4 weeks (n=6). Eighty-six percent of patients showed resolution within 4 weeks, and 100% showed clearance by 8 weeks. Twenty-two percent of patients had clearance within 3 weeks. There was no difference in the duration until resolution for those who had used oral or topical antibiotics.⁹ A different study suggested that low-potency topical steroids can be used to control inflammation when weaning patients off of strong steroids.⁵

Differential Diagnosis

The differential diagnosis should include acne vulgaris, allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis, impetigo, dermatophyte infection, rosacea, and angiofibromas.⁴

Acne vulgaris commonly is found in older adolescents, and unlike POD, it will present with open or closed comedones.² In patients aged 1 to 7 years, acne is a reason to consider endocrine evaluation. Allergic contact dermatitis is extremely pruritic, and the lesions often are papulovesicular with active weeping or crusting. Patients with irritant contact dermatitis often report burning and pain, and papules and pustules typically are absent. A thorough history can help rule out allergic or irritant contact dermatitis. Seborrheic dermatitis presents with erythema and scaling of the scalp, eyebrows, and nasolabial folds; it tends to spare the perioral regions and also lacks papules.² The lesions of impetigo typically have a yellow-brown exudate, which forms a honey-colored crust.²⁴ Tinea faciei, unlike the other tinea infections, can have an extremely variable presentation. Lesions usually begin as scaly macules that develop raised borders with central hypopigmentation, but papules, vesicles, and crusts can be seen.²⁵ Potassium hydroxide preparation can help diagnose a fungal infection. Rosacea presents with flushing of the central face regions, sometimes accompanied by papules, pustules, and telangiectases.² Although rare, physicians must rule out angiofibromas. Typically found in patients older than 5 years, angiofibromas are pink or flesh-colored papules often found on the nasolabial folds, cheeks, and chin.² Many angiofibromas can be associated with tuberous sclerosis.

Conclusion

Diagnosis of POD is clinical and rests upon the finding of erythematous papules on the face near the eyes, mouth, and nose. Extrafacial lesions also have been described, particularly in pediatric patients with CGPD. Many patients will report a history of atopic dermatitis and asthma. Therapy for POD includes both topical and systemic agents. For those with mild disease, topical metronidazole commonly is used. For patients requiring oral antibiotics, tetracyclines or macrolides can be prescribed based on the age of the patient. Many pediatric patients who begin with both oral and topical agents can later be maintained on topical therapy, sometimes with a low-dose oral antibiotic. Periorificial dermatitis has an excellent prognosis and most pediatric patients show marked improvement within weeks to months.

Perioral dermatitis is an acneform eruption presenting with erythematous papules, vesicles, and rarely pustules clustered around the orifices of the face. ¹ Lesions may be found near the eyes, mouth, and nose but typically spare the vermilion border of the lips. ² Nguyen and Eichenfield ³ preferred the term periorificial dermatitis (POD), which has since been adopted by others. ⁴ Patients may report pruritus, but there generally are no systemic symptoms unless patients have comorbid conditions such as atopic dermatitis. ⁵ Although this condition has been well examined in the literature on adults, data in the pediatric population are far more limited, consisting of case series and retrospective chart reviews. In 1979, Wilkinson et al ⁶ published a study of more than 200 patients with perioral dermatitis, but only 15 patients younger than 12 years were included.

Etiology

Although the exact pathogenesis of POD is unknown, a common denominator among many patients is prior exposure to topical corticosteroids.^3,7-9 Periorificial dermatitis also has been linked to the use of systemic corticosteroids in pediatric patients.¹⁰ The exact relationship between steroid use and dermatitis is unknown; it may be related to a change in the flora of hair follicles and in particular an association with fusiform bacteria–rich conditions.¹¹ Aside from steroid exposure, POD has been associated with the use of physical sunscreen in pediatric patients with dry skin,¹² rosin in chewing gum,¹³ and inhaled corticosteroids in those with asthma.¹⁴ In one case, a 15-year-old adolescent girl developed POD and swelling of the lips after 2 years of playing a flute made of cocus wood.^15,16

Epidemiology

In the largest chart review to date in the US pediatric population, Goel et al¹⁷ examined the clinical course of POD in 222 patients aged 3 months to 18 years at the Dermatology Clinic at the University of North Carolina Chapel Hill between June 2002 and March 2014. Consistent with prior studies, females seemed to be slightly more affected than males (55.4% vs 44.6%).¹⁷ Similarly, the patient population for a study conducted by Nguyen and Eichenfield³ consisted of more females (58% [46/79]) than males (42% [33/79]). Weston and Morelli⁹ conducted a retrospective chart review of steroid rosacea in 106 patients younger than 13 years, which included 29 patients younger than 3 years; the study included 46 males and 60 females.

Comorbidities and Family History

Goel et al¹⁷ (N=222) reported the following comorbidities associated with pediatric POD: atopic dermatitis (29.3%), asthma (14.9%), and allergies (9.9%). Steroid exposure was noted in 58.1% of patients.¹⁷ Similarly, Nguyen and Eichenfield³ (N=79) found that the most common comorbidities were atopic dermatitis (14%), keratosis pilaris (14%), viral infections (14%), acne (10%), and seborrheic dermatitis (10%). Family history of atopy was noted in 55% of patients and family history of rosacea was noted in 3%. In a case series of 11 pediatric patients, 3 (27%) had keratosis pilaris, 7 (64%) had a family history of atopy, and 2 (18%) had a family history of rosacea.⁸ Weston and Morelli⁹ found a much higher incidence of familial rosacea (20%) in 106 children with steroid rosacea. It is hard to interpret the role of genetic tendency in rosacea, as different populations have different background prevalence of rosacea and atopic dermatitis (ie, rosacea is immensely more common in white individuals).

Clinical Presentation

Periorificial dermatitis generally presents with small, pink- to flesh-colored papules in a perioral, periocular, and perinasal distribution. Although many patients are white, a particularly prominent variant has been noted in black children with papules that may be hyperpigmented.¹⁸ In a 2006 chart review in 79 pediatric POD patients aged 6 months to 18 years, Nguyen and Eichenfield³ reported that 92% (73/79) of patients presented for a facial rash with an average duration ranging from 2 weeks to 4 years. Interestingly, although Tempark and Shwayder¹ did not report burning associated with pediatric POD, Nguyen and Eichenfield³ found that 19% of patients reported pruritus and 4% reported burning or tenderness. Seventy-two percent of patients had been exposed to steroids for treatment of their dermatitis. Seventy percent had perioral involvement, 43% had perinasal involvement, 25% had periocular involvement, and 1% had a perivulvar rash; 64% of patients only had perioral, perinasal, and periocular involvement. In others, lesions also were found on the cheeks, chin, neck, and forehead. Perioral lesions were more likely to be found in patients younger than 5 years compared to those who were at least 5 years of age. Eighty-six percent of patients had erythema with or without scaling, 66% had papules, and 11% had pustules. Fewer than 3% had lichenification, telangiectases, or changes in pigmentation.³

Boeck et al¹⁹ described 7 pediatric patients with perioral dermatitis. Six (86%) patients had perioral lesions, and 6 (86%) had previously been treated with moderate- to high-potency topical corticosteroids. Skin prick tests were negative in 6 (86%) patients.¹⁹ In one case report, a 6-year-old boy did not present with the classic acneform lesions but rather sharply demarcated eczematous patches around the eyes, nose, and mouth. The rash began to fade after 2 weeks of using metronidazole gel 1%, and after 4 months he was only left with mild hyperpigmentation.⁴

Periorificial dermatitis was once thought to be a juvenile form of rosacea.⁵ In 1972, Savin et al⁸ described 11 pediatric patients with “rosacea-like” facial flushing, papules, pustules, and scaling over the cheeks, forehead, and chin. In some patients, the eyelids also were involved. At least 8 patients had been using potent topical corticosteroids and had noticed exacerbation of their skin lesions after stopping therapy.⁸

Variants of POD

Several other variants of POD have been described in pediatric patients including childhood granulomatous periorificial dermatitis (CGPD)(also known as facial Afro-Caribbean [childhood] eruption) and lupus miliaris disseminatus faciei. Childhood granulomatous periorificial dermatitis presents in prepubertal children as dome-shaped, red to yellow-brown, monomorphous papules around the eyes, nose, and mouth; there are no systemic findings.^20,21 It occurs equally in males and females and is more commonly seen in dark-skinned patients. Childhood granulomatous periorificial dermatitis usually resolves within a few months to years but may be associated with blepharitis or conjunctivitis.²⁰ Urbatsch et al²⁰ analyzed extrafacial lesions in 8 patients (aged 2–12 years) with CGPD. Lesions were found on the trunk (38% [3/8]), neck (25% [2/8]), ears (25% [2/8]), extremities (50% [4/8]), labia majora (38% [3/8]), and abdomen (13% [1/8]). In addition, 2 (25% [2/8]) patients had blepharitis.²⁰

Lupus miliaris disseminatus faciei, which occurs in adolescents and adults, commonly involves the eyelids and central areas of the face such as the nose and upper lips. Patients typically present with erythematous or flesh-colored papules.¹

Diagnosis

Diagnosis of POD is made clinically based on the observation of papules (and sometimes pustules) around the orifices of the face, sparing the vermilion border, together with a lack of comedones.¹⁷ Laboratory tests are not useful.⁵ Biopsies rarely are performed, and the results mimic those of rosacea, demonstrating a perifollicular lymphohistiocytic infiltrate, epithelioid cells, and occasionally giant cells.^5,22,23 Early papular lesions can show mild acanthosis, epidermal edema, and parakeratosis.²³ Biopsies in patients with CGPD reveal noncaseating perifollicular granulomas.²⁰

Treatment and Clinical Outcome

Although topical corticosteroids can improve facial lesions in pediatric POD, the eruption often rebounds when therapy is discontinued.¹ One therapy frequently used in adults is oral tetracyclines; however, these agents must not be used in patients younger than 9 years due to potential dental staining.⁴ The standards are either topical metronidazole twice daily with clearance in 3 to 8 weeks or oral erythromycin.⁷

In the review conducted by Goel et al,¹⁷ treatment included azithromycin (44.6%), topical metronidazole (42.3%), sodium sulfacetamide lotion (35.6%), oral antibiotic monotherapy (15.3%), topical agent monotherapy (44.6%), and combined oral and topical agent therapy (40.1%). Of those patients who presented for a follow-up visit (59%), 72% of cases resolved and 10.7% showed some improvement. For those patients who returned for follow-up, the average duration until symptom resolution was approximately 4 months. The most common side effects were pigmentation changes (1.8%), worsening of symptoms (1.8%), gastrointestinal upset (0.9%), irritant dermatitis (0.9%), and xerosis (0.5%).¹⁷

Changes were made to the treatment plans for 16 patients, most often due to inadequate treatment response.¹⁷ Five patients treated with sodium sulfacetamide lotion also were started on oral azithromycin. Four patients treated with oral antibiotics were given a topical agent (metronidazole or sodium sulfacetamide lotion). Other modifications included replacing sodium sulfacetamide lotion with topical metronidazole and an oral antibiotic (azithromycin or doxycycline, n=3), adjusting the doses of oral or topical medications (n=2), adding tacrolimus (n=1), and replacing topical metronidazole with sodium sulfacetamide lotion (n=1). Of the patients who underwent a change in treatment plan, 5 experienced symptom recurrence, 4 had mild improvement, and 1 patient had no improvement. Six patients were lost to follow-up.¹⁷

In the study conducted by Nguyen and Eichenfield,³ follow-up visits occurred approximately 3 months after the first visit. Fifty-two percent of patients used metronidazole alone or with another medication; for most of these patients, the POD cleared an average of 7 weeks after starting treatment, ranging from 1 to 24 weeks. The use of topical calcineurin inhibitors, sulfacetamide, hydrocortisone, or antifungal therapies was associated with persistence of the rash at the follow-up visit. In contrast, the use of metronidazole and/or oral erythromycin was associated with resolution of the rash at the follow-up visit. The investigators recommended the following regimen: topical metronidazole for 1 to 2 months and, if necessary, the addition of oral erythromycin.³

In the case series by Boeck et al,¹⁹ all patients were started on metronidazole gel 1% applied once daily for the first week, and then twice daily until the lesions resolved. All patients showed improvement after 4 to 6 weeks, and eventually the disease cleared between 3 and 6 months. All patients were still symptom free during a 2-year observation period.¹⁹

Manders and Lucky⁷ described 14 patients with POD (aged 9 months to 6.5 years). Eight patients used only metronidazole gel 0.75%, while 5 used the gel in combination with topical corticosteroids (21% [3/14]), oral erythromycin (7% [1/14]), or topical erythromycin (7% [1/14]); 1 patient remained on hydrocortisone 1% and cleared. Patients responded well within 1 to 8 weeks and were symptom free for up to 16 months. Mid- to high-potency steroids were discontinued in all patients.⁷

In some pediatric patients with CGPD, recovery occurs faster with the use of oral macrolides or tetracyclines, either alone or in combination with topical antibiotics or sulfur-based lotions.²⁰ Extrafacial lesions associated with CGPD do not appear to negatively impact treatment response or duration of disease. In the review conducted by Urbatsch et al,²⁰ 7 of 8 (88%) CGPD patients with extrafacial lesions were treated with oral agents including erythromycin, hydroxychloroquine, cyclosporine, minocycline, and azithromycin. Most of these patients also were using topical agents such as triamcinolone acetonide, desonide, metronidazole, and erythromycin. The time to resolution ranged from several weeks to 6 months.²⁰

Weston and Morelli⁹ described a treatment regimen for steroid rosacea. The study included data on 106 children (60 females, 46 males) who had been exposed to mostly class 7 low-potency agents. All patients were advised to immediately stop topical steroid therapy without gradual withdrawal and to begin oral erythromycin stearate 30 mg/kg daily in 2 doses per day for 4 weeks. Patients who were unable to tolerate erythromycin were advised to use topical clindamycin phosphate twice daily for 4 weeks (n=6). Eighty-six percent of patients showed resolution within 4 weeks, and 100% showed clearance by 8 weeks. Twenty-two percent of patients had clearance within 3 weeks. There was no difference in the duration until resolution for those who had used oral or topical antibiotics.⁹ A different study suggested that low-potency topical steroids can be used to control inflammation when weaning patients off of strong steroids.⁵

Differential Diagnosis

The differential diagnosis should include acne vulgaris, allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis, impetigo, dermatophyte infection, rosacea, and angiofibromas.⁴

Acne vulgaris commonly is found in older adolescents, and unlike POD, it will present with open or closed comedones.² In patients aged 1 to 7 years, acne is a reason to consider endocrine evaluation. Allergic contact dermatitis is extremely pruritic, and the lesions often are papulovesicular with active weeping or crusting. Patients with irritant contact dermatitis often report burning and pain, and papules and pustules typically are absent. A thorough history can help rule out allergic or irritant contact dermatitis. Seborrheic dermatitis presents with erythema and scaling of the scalp, eyebrows, and nasolabial folds; it tends to spare the perioral regions and also lacks papules.² The lesions of impetigo typically have a yellow-brown exudate, which forms a honey-colored crust.²⁴ Tinea faciei, unlike the other tinea infections, can have an extremely variable presentation. Lesions usually begin as scaly macules that develop raised borders with central hypopigmentation, but papules, vesicles, and crusts can be seen.²⁵ Potassium hydroxide preparation can help diagnose a fungal infection. Rosacea presents with flushing of the central face regions, sometimes accompanied by papules, pustules, and telangiectases.² Although rare, physicians must rule out angiofibromas. Typically found in patients older than 5 years, angiofibromas are pink or flesh-colored papules often found on the nasolabial folds, cheeks, and chin.² Many angiofibromas can be associated with tuberous sclerosis.

Conclusion

Diagnosis of POD is clinical and rests upon the finding of erythematous papules on the face near the eyes, mouth, and nose. Extrafacial lesions also have been described, particularly in pediatric patients with CGPD. Many patients will report a history of atopic dermatitis and asthma. Therapy for POD includes both topical and systemic agents. For those with mild disease, topical metronidazole commonly is used. For patients requiring oral antibiotics, tetracyclines or macrolides can be prescribed based on the age of the patient. Many pediatric patients who begin with both oral and topical agents can later be maintained on topical therapy, sometimes with a low-dose oral antibiotic. Periorificial dermatitis has an excellent prognosis and most pediatric patients show marked improvement within weeks to months.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

Physician diversity benefits patient care: Patients are more satisfied during race-concordant visits, report their physicians as more engaged and responsive to their needs, and experience notably longer visits.^1,2 Nonwhite physicians (ie, races and ethnicities that are underrepresented in medicine [URM] with respect to the general population) are more likely to care for underserved communities. Furthermore, increased diversity in the learning environment supports preparedness of all trainees to serve diverse patients.³ For these reasons, a more diverse physician workforce can contribute to better access to care in all communities, thus addressing health disparities.^1,4

Increasing diversity in the dermatology workforce has been identified as an emerging priority.⁵ Dermatology is one of the least diverse specialties,⁵ and the representation of URM dermatologists is lower compared to other medical specialties and the general US population. The proportion of specialty leaders from underrepresented backgrounds may be even smaller. The lack of diversity in academic dermatology has negative consequences for patients and communities. Increasing the diversity of resident trainees is the only way to improve the diversity gap within the dermatology workforce.⁶

Recent commentary on this topic has highlighted several priorities for addressing the dermatology diversity gap,^6-11 including the following: (1) making diversity an explicit goal in dermatology; (2) ensuring early exposure to dermatology in medical school; (3) supporting mentorship programs for minority medical students; (4) increasing medical student diversity; (5) encouraging that all dermatology program directors and leaders train in implicit bias; and (6) reviewing residency admission criteria to ensure they are objective and equitable, not biased against any applicants.

The process of reviewing residency selection criteria has begun. In 2017, Chen and Shinkai⁷ called for our specialty to rethink the selection process. The authors argued that emphasis on test scores, grades, and publications systematically disadvantages underrepresented minorities and students from lower socioeconomic statuses. The authors proposed several solutions: (1) make diversity an explicit goal of the selection process, (2) shift away from test scores for all applicants, (3) change the interview format, (4) prioritize other competencies such as observation skills, and (5) recruit and retain faculty who support URM trainees.⁷

Several dermatology leadership groups have taken action to promote programs that aim to improve diversity within dermatology. The Dermatology Diversity Champions initiative includes 6 US dermatology residency programs that are committed to increasing diversity and collaborate to evaluate pilot approaches. The American Academy of Dermatology President’s Conference on Diversity in Dermatology in Chicago, Illinois, in August 2017, as well as the focus on diversity in residency training programs at the Annual Meeting of the Association of Professors of Dermatology in Chicago, Illinois, in October 2017, are strong indicators that our specialty as a whole is aware and eager to embrace diversity as a priority. The American Academy of Dermatology President’s Conference, which was comprised of representatives from many leadership organizations and interest groups within dermatology, identified 3 action items: (1) increase the pipeline of URM students into medical school, (2) increase interest in dermatology among URM medical students, and (3) increase URM representation in residency training programs.

There are many strengths, weaknesses, opportunities, and threats/barriers (SWOT) to attaining this goal. Current strengths include strong support from dermatology leaders and activities that build on existing mentorship and diversity efforts by leaders within our specialty. SWOT analysis highlights several key opportunities of this mission, including connecting with the House of Medicine in shared efforts to improve diversity, as well as increased understanding of skin of color, health disparities, and implicit bias among physicians. Although faculty development will require time and financial investment, it will lead to tremendous benefits and opportunities for all dermatologists, including URM physicians. Other weaknesses and threats/barriers are outlined in the Figure.

Final Thoughts

We are far from reaching our goal of a diverse dermatology workforce, and the road ahead is long. We have a start and we have momentum. We can move forward by spreading the word that all types of diversity are a priority for our specialty. Making a true difference will require commitment and sustained efforts. Dermatology can lead the way as all of American medicine strives to attain workforce diversity.

Physician diversity benefits patient care: Patients are more satisfied during race-concordant visits, report their physicians as more engaged and responsive to their needs, and experience notably longer visits.^1,2 Nonwhite physicians (ie, races and ethnicities that are underrepresented in medicine [URM] with respect to the general population) are more likely to care for underserved communities. Furthermore, increased diversity in the learning environment supports preparedness of all trainees to serve diverse patients.³ For these reasons, a more diverse physician workforce can contribute to better access to care in all communities, thus addressing health disparities.^1,4

Increasing diversity in the dermatology workforce has been identified as an emerging priority.⁵ Dermatology is one of the least diverse specialties,⁵ and the representation of URM dermatologists is lower compared to other medical specialties and the general US population. The proportion of specialty leaders from underrepresented backgrounds may be even smaller. The lack of diversity in academic dermatology has negative consequences for patients and communities. Increasing the diversity of resident trainees is the only way to improve the diversity gap within the dermatology workforce.⁶

Recent commentary on this topic has highlighted several priorities for addressing the dermatology diversity gap,^6-11 including the following: (1) making diversity an explicit goal in dermatology; (2) ensuring early exposure to dermatology in medical school; (3) supporting mentorship programs for minority medical students; (4) increasing medical student diversity; (5) encouraging that all dermatology program directors and leaders train in implicit bias; and (6) reviewing residency admission criteria to ensure they are objective and equitable, not biased against any applicants.

The process of reviewing residency selection criteria has begun. In 2017, Chen and Shinkai⁷ called for our specialty to rethink the selection process. The authors argued that emphasis on test scores, grades, and publications systematically disadvantages underrepresented minorities and students from lower socioeconomic statuses. The authors proposed several solutions: (1) make diversity an explicit goal of the selection process, (2) shift away from test scores for all applicants, (3) change the interview format, (4) prioritize other competencies such as observation skills, and (5) recruit and retain faculty who support URM trainees.⁷

Several dermatology leadership groups have taken action to promote programs that aim to improve diversity within dermatology. The Dermatology Diversity Champions initiative includes 6 US dermatology residency programs that are committed to increasing diversity and collaborate to evaluate pilot approaches. The American Academy of Dermatology President’s Conference on Diversity in Dermatology in Chicago, Illinois, in August 2017, as well as the focus on diversity in residency training programs at the Annual Meeting of the Association of Professors of Dermatology in Chicago, Illinois, in October 2017, are strong indicators that our specialty as a whole is aware and eager to embrace diversity as a priority. The American Academy of Dermatology President’s Conference, which was comprised of representatives from many leadership organizations and interest groups within dermatology, identified 3 action items: (1) increase the pipeline of URM students into medical school, (2) increase interest in dermatology among URM medical students, and (3) increase URM representation in residency training programs.

There are many strengths, weaknesses, opportunities, and threats/barriers (SWOT) to attaining this goal. Current strengths include strong support from dermatology leaders and activities that build on existing mentorship and diversity efforts by leaders within our specialty. SWOT analysis highlights several key opportunities of this mission, including connecting with the House of Medicine in shared efforts to improve diversity, as well as increased understanding of skin of color, health disparities, and implicit bias among physicians. Although faculty development will require time and financial investment, it will lead to tremendous benefits and opportunities for all dermatologists, including URM physicians. Other weaknesses and threats/barriers are outlined in the Figure.

Final Thoughts

We are far from reaching our goal of a diverse dermatology workforce, and the road ahead is long. We have a start and we have momentum. We can move forward by spreading the word that all types of diversity are a priority for our specialty. Making a true difference will require commitment and sustained efforts. Dermatology can lead the way as all of American medicine strives to attain workforce diversity.

Physician diversity benefits patient care: Patients are more satisfied during race-concordant visits, report their physicians as more engaged and responsive to their needs, and experience notably longer visits.^1,2 Nonwhite physicians (ie, races and ethnicities that are underrepresented in medicine [URM] with respect to the general population) are more likely to care for underserved communities. Furthermore, increased diversity in the learning environment supports preparedness of all trainees to serve diverse patients.³ For these reasons, a more diverse physician workforce can contribute to better access to care in all communities, thus addressing health disparities.^1,4

Increasing diversity in the dermatology workforce has been identified as an emerging priority.⁵ Dermatology is one of the least diverse specialties,⁵ and the representation of URM dermatologists is lower compared to other medical specialties and the general US population. The proportion of specialty leaders from underrepresented backgrounds may be even smaller. The lack of diversity in academic dermatology has negative consequences for patients and communities. Increasing the diversity of resident trainees is the only way to improve the diversity gap within the dermatology workforce.⁶

Recent commentary on this topic has highlighted several priorities for addressing the dermatology diversity gap,^6-11 including the following: (1) making diversity an explicit goal in dermatology; (2) ensuring early exposure to dermatology in medical school; (3) supporting mentorship programs for minority medical students; (4) increasing medical student diversity; (5) encouraging that all dermatology program directors and leaders train in implicit bias; and (6) reviewing residency admission criteria to ensure they are objective and equitable, not biased against any applicants.

The process of reviewing residency selection criteria has begun. In 2017, Chen and Shinkai⁷ called for our specialty to rethink the selection process. The authors argued that emphasis on test scores, grades, and publications systematically disadvantages underrepresented minorities and students from lower socioeconomic statuses. The authors proposed several solutions: (1) make diversity an explicit goal of the selection process, (2) shift away from test scores for all applicants, (3) change the interview format, (4) prioritize other competencies such as observation skills, and (5) recruit and retain faculty who support URM trainees.⁷

Several dermatology leadership groups have taken action to promote programs that aim to improve diversity within dermatology. The Dermatology Diversity Champions initiative includes 6 US dermatology residency programs that are committed to increasing diversity and collaborate to evaluate pilot approaches. The American Academy of Dermatology President’s Conference on Diversity in Dermatology in Chicago, Illinois, in August 2017, as well as the focus on diversity in residency training programs at the Annual Meeting of the Association of Professors of Dermatology in Chicago, Illinois, in October 2017, are strong indicators that our specialty as a whole is aware and eager to embrace diversity as a priority. The American Academy of Dermatology President’s Conference, which was comprised of representatives from many leadership organizations and interest groups within dermatology, identified 3 action items: (1) increase the pipeline of URM students into medical school, (2) increase interest in dermatology among URM medical students, and (3) increase URM representation in residency training programs.

There are many strengths, weaknesses, opportunities, and threats/barriers (SWOT) to attaining this goal. Current strengths include strong support from dermatology leaders and activities that build on existing mentorship and diversity efforts by leaders within our specialty. SWOT analysis highlights several key opportunities of this mission, including connecting with the House of Medicine in shared efforts to improve diversity, as well as increased understanding of skin of color, health disparities, and implicit bias among physicians. Although faculty development will require time and financial investment, it will lead to tremendous benefits and opportunities for all dermatologists, including URM physicians. Other weaknesses and threats/barriers are outlined in the Figure.

Final Thoughts

We are far from reaching our goal of a diverse dermatology workforce, and the road ahead is long. We have a start and we have momentum. We can move forward by spreading the word that all types of diversity are a priority for our specialty. Making a true difference will require commitment and sustained efforts. Dermatology can lead the way as all of American medicine strives to attain workforce diversity.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.¹ As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.² Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.³ Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.² In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.³ The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.³ High BP-3 concentrations have also been recorded in the waters off the Canary Islands,⁴ Hawaii,³ and South Carolina.⁵

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.⁶ In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.⁷ Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.⁸ Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.⁹ Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.^10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,¹² and filter-feeding organisms, including marine abalone¹³ and the Mediterranean mussel.¹⁴ These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.¹⁵

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.¹⁶ When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.¹⁵ Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.¹⁷ One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.¹ As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.² Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.³ Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.² In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.³ The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.³ High BP-3 concentrations have also been recorded in the waters off the Canary Islands,⁴ Hawaii,³ and South Carolina.⁵

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.⁶ In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.⁷ Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.⁸ Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.⁹ Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.^10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,¹² and filter-feeding organisms, including marine abalone¹³ and the Mediterranean mussel.¹⁴ These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.¹⁵

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.¹⁶ When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.¹⁵ Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.¹⁷ One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.¹ As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.² Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.³ Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.² In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.³ The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.³ High BP-3 concentrations have also been recorded in the waters off the Canary Islands,⁴ Hawaii,³ and South Carolina.⁵

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.⁶ In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.⁷ Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.⁸ Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.⁹ Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.^10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,¹² and filter-feeding organisms, including marine abalone¹³ and the Mediterranean mussel.¹⁴ These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.¹⁵

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.¹⁶ When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.¹⁵ Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.¹⁷ One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

The Diagnosis: Fibroblastic Rheumatism

Routine histologic sections stained with hematoxylin and eosin demonstrated a noncircumscribed dermal proliferation of fibroblasts and myofibroblasts with thickened collagen bundles (Figure, A and B). Focally fragmented elastin fibers were noted with Verhoeff elastic tissue stain. Alcian blue stain did not show increased dermal mucin. With the clinical presentation and histologic findings described, we diagnosed the patient with fibroblastic rheumatism (FR). To date, the patient's condition has stabilized overall with skin lesions fading and minimal to no joint pain. Current therapies include adalimumab, mycophenolate mofetil 500 mg 3 times daily, and low-dose prednisone.

Fibroblastic rheumatism is a rare arthropathy with cutaneous findings initially described by Chaouat et al¹ in 1980. Age of onset varies, and the condition also has been observed in pediatric patients.² Fibroblastic rheumatism is characterized by sudden onset of firm, flesh-colored, subcutaneous nodules on periungual and periarticular surfaces.² Neck lesions rarely are described,^2-4 and cordlike plaques previously have not been reported in FR. Typically, patients develop diffusely swollen fingers, palmar thickening, sclerodactyly, and contractures. The eruption may be accompanied by Raynaud phenomenon as well as a progressive symmetric erosive arthropathy.^2,5

The clinical course in FR is variable. The cutaneous findings spontaneously may regress in months to years.^3,4 However, polyarthropathy often is destructive and progresses to disability.³ Response to therapy has been unpredictable, and the following treatments have been tried, generally with poor efficacy: aspirin, nonsteroidal anti-inflammatory drugs, hydroxychloroquine, colchicine, methotrexate, prednisone, infliximab, D-penicillamine, interferon alfa, and intensive physical therapy.^2-4,6 Histologic characteristics may include thickened collagen bundles along with a fibroblastic and myofibroblastic proliferation. Elastic fibers may be decreased or absent.^2,3,5

Clinical and histologic features in FR may mimic other entities; thus, clinical pathological correlation is essential in determining the correct diagnosis. Considerations in the differential diagnoses include multicentric reticulohistiocytosis (MRH), palisaded neutrophilic and granulomatous dermatitis, and scleroderma.

In MRH, a symmetric erosive arthritis of mainly distal interphalangeal joints typically precedes the cutaneous disease. Occurrence of arthritis mutilans is reported in approximately half of patients.⁴ Cutaneous manifestations typically include the presence of coral bead-like papules and nodules over the dorsal aspect of the hands, face, and neck. Unlike FR, MRH has a concomitant autoimmune disease in up to 20% of cases and an associated malignancy in up to 31% of cases, with breast and ovarian carcinomas most common. On histology, MRH is characterized by a nodular infiltrate of histiocytes and multinucleated giant cells with eosinophilic ground-glass cytoplasm.⁴ No notable collagen changes or fibroblastic proliferations typically are present.

Palisaded neutrophilic and granulomatous dermatitis, usually associated with rheumatoid arthritis or connective tissue disease, classically presents as annular plaques and indurated linear bands over the trunk and extremities. However, its clinical presentation is quite variable and may include pink to violaceous urticarialike; livedoid-appearing; or nonspecific papules, plaques, or nodules. Histology in palisaded neutrophilic and granulomatous dermatitis shows a dense dermal neutrophilic infiltrate associated with interstitial histiocytes having a palisading arrangement around degenerated collagen.⁷ No fibroblastic proliferation typically is present.

Scleroderma can be distinguished based on additional clinical and laboratory findings as well as histology showing thickened collagen bundles without fibroblastic proliferation.2 The histologic findings also may suggest inclusion of dermatofibroma or a scar in the differential diagnosis, though the clinical presentation of these entities would not support these diagnoses.  
 
Acknowledgments
We thank the patient for granting permission to share this information. We also thank Sheng Chen, MD, PhD (Lake Success, New York), for his dermatopathological contributions to the case.

The Diagnosis: Fibroblastic Rheumatism

Routine histologic sections stained with hematoxylin and eosin demonstrated a noncircumscribed dermal proliferation of fibroblasts and myofibroblasts with thickened collagen bundles (Figure, A and B). Focally fragmented elastin fibers were noted with Verhoeff elastic tissue stain. Alcian blue stain did not show increased dermal mucin. With the clinical presentation and histologic findings described, we diagnosed the patient with fibroblastic rheumatism (FR). To date, the patient's condition has stabilized overall with skin lesions fading and minimal to no joint pain. Current therapies include adalimumab, mycophenolate mofetil 500 mg 3 times daily, and low-dose prednisone.

Fibroblastic rheumatism is a rare arthropathy with cutaneous findings initially described by Chaouat et al¹ in 1980. Age of onset varies, and the condition also has been observed in pediatric patients.² Fibroblastic rheumatism is characterized by sudden onset of firm, flesh-colored, subcutaneous nodules on periungual and periarticular surfaces.² Neck lesions rarely are described,^2-4 and cordlike plaques previously have not been reported in FR. Typically, patients develop diffusely swollen fingers, palmar thickening, sclerodactyly, and contractures. The eruption may be accompanied by Raynaud phenomenon as well as a progressive symmetric erosive arthropathy.^2,5

The clinical course in FR is variable. The cutaneous findings spontaneously may regress in months to years.^3,4 However, polyarthropathy often is destructive and progresses to disability.³ Response to therapy has been unpredictable, and the following treatments have been tried, generally with poor efficacy: aspirin, nonsteroidal anti-inflammatory drugs, hydroxychloroquine, colchicine, methotrexate, prednisone, infliximab, D-penicillamine, interferon alfa, and intensive physical therapy.^2-4,6 Histologic characteristics may include thickened collagen bundles along with a fibroblastic and myofibroblastic proliferation. Elastic fibers may be decreased or absent.^2,3,5

Clinical and histologic features in FR may mimic other entities; thus, clinical pathological correlation is essential in determining the correct diagnosis. Considerations in the differential diagnoses include multicentric reticulohistiocytosis (MRH), palisaded neutrophilic and granulomatous dermatitis, and scleroderma.

In MRH, a symmetric erosive arthritis of mainly distal interphalangeal joints typically precedes the cutaneous disease. Occurrence of arthritis mutilans is reported in approximately half of patients.⁴ Cutaneous manifestations typically include the presence of coral bead-like papules and nodules over the dorsal aspect of the hands, face, and neck. Unlike FR, MRH has a concomitant autoimmune disease in up to 20% of cases and an associated malignancy in up to 31% of cases, with breast and ovarian carcinomas most common. On histology, MRH is characterized by a nodular infiltrate of histiocytes and multinucleated giant cells with eosinophilic ground-glass cytoplasm.⁴ No notable collagen changes or fibroblastic proliferations typically are present.

Palisaded neutrophilic and granulomatous dermatitis, usually associated with rheumatoid arthritis or connective tissue disease, classically presents as annular plaques and indurated linear bands over the trunk and extremities. However, its clinical presentation is quite variable and may include pink to violaceous urticarialike; livedoid-appearing; or nonspecific papules, plaques, or nodules. Histology in palisaded neutrophilic and granulomatous dermatitis shows a dense dermal neutrophilic infiltrate associated with interstitial histiocytes having a palisading arrangement around degenerated collagen.⁷ No fibroblastic proliferation typically is present.

Scleroderma can be distinguished based on additional clinical and laboratory findings as well as histology showing thickened collagen bundles without fibroblastic proliferation.2 The histologic findings also may suggest inclusion of dermatofibroma or a scar in the differential diagnosis, though the clinical presentation of these entities would not support these diagnoses.  
 
Acknowledgments
We thank the patient for granting permission to share this information. We also thank Sheng Chen, MD, PhD (Lake Success, New York), for his dermatopathological contributions to the case.

The Diagnosis: Fibroblastic Rheumatism

Routine histologic sections stained with hematoxylin and eosin demonstrated a noncircumscribed dermal proliferation of fibroblasts and myofibroblasts with thickened collagen bundles (Figure, A and B). Focally fragmented elastin fibers were noted with Verhoeff elastic tissue stain. Alcian blue stain did not show increased dermal mucin. With the clinical presentation and histologic findings described, we diagnosed the patient with fibroblastic rheumatism (FR). To date, the patient's condition has stabilized overall with skin lesions fading and minimal to no joint pain. Current therapies include adalimumab, mycophenolate mofetil 500 mg 3 times daily, and low-dose prednisone.

Fibroblastic rheumatism is a rare arthropathy with cutaneous findings initially described by Chaouat et al¹ in 1980. Age of onset varies, and the condition also has been observed in pediatric patients.² Fibroblastic rheumatism is characterized by sudden onset of firm, flesh-colored, subcutaneous nodules on periungual and periarticular surfaces.² Neck lesions rarely are described,^2-4 and cordlike plaques previously have not been reported in FR. Typically, patients develop diffusely swollen fingers, palmar thickening, sclerodactyly, and contractures. The eruption may be accompanied by Raynaud phenomenon as well as a progressive symmetric erosive arthropathy.^2,5

The clinical course in FR is variable. The cutaneous findings spontaneously may regress in months to years.^3,4 However, polyarthropathy often is destructive and progresses to disability.³ Response to therapy has been unpredictable, and the following treatments have been tried, generally with poor efficacy: aspirin, nonsteroidal anti-inflammatory drugs, hydroxychloroquine, colchicine, methotrexate, prednisone, infliximab, D-penicillamine, interferon alfa, and intensive physical therapy.^2-4,6 Histologic characteristics may include thickened collagen bundles along with a fibroblastic and myofibroblastic proliferation. Elastic fibers may be decreased or absent.^2,3,5

Clinical and histologic features in FR may mimic other entities; thus, clinical pathological correlation is essential in determining the correct diagnosis. Considerations in the differential diagnoses include multicentric reticulohistiocytosis (MRH), palisaded neutrophilic and granulomatous dermatitis, and scleroderma.

In MRH, a symmetric erosive arthritis of mainly distal interphalangeal joints typically precedes the cutaneous disease. Occurrence of arthritis mutilans is reported in approximately half of patients.⁴ Cutaneous manifestations typically include the presence of coral bead-like papules and nodules over the dorsal aspect of the hands, face, and neck. Unlike FR, MRH has a concomitant autoimmune disease in up to 20% of cases and an associated malignancy in up to 31% of cases, with breast and ovarian carcinomas most common. On histology, MRH is characterized by a nodular infiltrate of histiocytes and multinucleated giant cells with eosinophilic ground-glass cytoplasm.⁴ No notable collagen changes or fibroblastic proliferations typically are present.

Palisaded neutrophilic and granulomatous dermatitis, usually associated with rheumatoid arthritis or connective tissue disease, classically presents as annular plaques and indurated linear bands over the trunk and extremities. However, its clinical presentation is quite variable and may include pink to violaceous urticarialike; livedoid-appearing; or nonspecific papules, plaques, or nodules. Histology in palisaded neutrophilic and granulomatous dermatitis shows a dense dermal neutrophilic infiltrate associated with interstitial histiocytes having a palisading arrangement around degenerated collagen.⁷ No fibroblastic proliferation typically is present.

Scleroderma can be distinguished based on additional clinical and laboratory findings as well as histology showing thickened collagen bundles without fibroblastic proliferation.2 The histologic findings also may suggest inclusion of dermatofibroma or a scar in the differential diagnosis, though the clinical presentation of these entities would not support these diagnoses.  
 
Acknowledgments
We thank the patient for granting permission to share this information. We also thank Sheng Chen, MD, PhD (Lake Success, New York), for his dermatopathological contributions to the case.

The Diagnosis: Microcystic Adnexal Carcinoma

Microcystic adnexal carcinoma (MAC) is a rare, low-grade adnexal carcinoma consisting of both ductal and pilar differentiation.¹ It typically presents in young to middle-aged adults as a flesh-colored or yellow indurated plaque on the upper lip, medial cheek, or chin. Histologically, MACs exhibit a biphasic pattern consisting of epithelial islands of cords and lumina creating tadpolelike ducts intermixed with basaloid nests (quiz image). Keratin horn cysts are common superficially. A dense red sclerotic stroma is seen interspersed between the ducts and epithelial islands creating a "paisley tie" appearance. The lesion displays an infiltrative pattern and can be deeply invasive, extending down to the fat and muscle (quiz image, inset). Perineural invasion is common. Atypia, when present, is minimal or mild and mitoses are rare. Although this tumor's histologic pattern appears aggressive in nature, it lacks immunohistochemical staining such as p53, Ki-67, bcl-2, and c-erbB-2 that correlate with malignant behavior.² A common diagnostic pitfall is examination of a superficial biopsy in which an MAC may be mistakenly identified as another entity.

Syringomas are benign adnexal neoplasms with ductal differentiation.³ They are more common in women, especially those of Asian descent, and in patients with Down syndrome. They typically present as multiple small, firm, flesh-colored papules in the periorbital area or upper trunk. Histologically, syringomas also display comma-shaped tubules and ducts with a tadpolelike appearance and a dense red stroma creating a paisley tie-like pattern. Ductal cells have an abundant pink cytoplasm. Syringomas are well-circumscribed and more superficial than MACs without an infiltrative pattern. They lack mitotic activity or perineural invasion (Figure 1).

Desmoplastic trichoepithelioma (DTE) is a benign follicular neoplasm.⁴ It presents in adulthood with a female predominance. Clinically, it appears as a solitary flesh-colored to yellow annular plaque with raised borders and a depressed central area, often on the medial cheek. Histologically, DTEs are well-circumscribed with narrow branching cords lined with polygonal cells. A dense red stroma in combination with the epithelioid aggregates also creates the paisley tie-like pattern in this lesion. Retraction between collagen bundles within the stroma can be seen, helping distinguish this lesion from a morpheaform basal cell carcinoma (BCC), which has retraction between the epithelium and stroma. Immunohistochemistry also can be a useful tool to help differentiate DTEs from morpheaform BCCs in that sparse cytokeratin 20-positive Merkel cells can be seen within the basaloid islands of DTE but not BCC.⁵ Also seen with DTEs are numerous keratin horn cysts that commonly are filled with dystrophic calcifications. Cellular atypia and mitoses are not seen (Figure 2). Compared to MACs, DTEs lack abundant ductal structures and also contain papillary mesenchymal bodies and a more fibroblast-rich stroma.

Morpheaform BCC is an aggressive subtype of BCC. It presents as a scarlike plaque that gradually expands. Thin infiltrating strands of basaloid cells are seen haphazardly throughout a pink sclerotic stroma. Tadpolelike basaloid islands and rarely horn cysts can be seen scattered superficially, creating the paisley tie-like pattern. This lesion is more infiltrating than a syringoma or a DTE, and perineural invasion is common. Retraction is uncommon, but when present, it is seen between the epithelial cords and adjacent stroma (Figure 3).

Trichoadenoma is another benign neoplasm of follicular differentiation.⁶ It typically presents as a dome-shaped papule or plaque on the head or neck. Histologically it displays numerous dilated cystic spaces that reflect its origin from isthmic and infundibular differentiation. There is no attachment to the overlying epidermis. It can be distinguished from MAC, DTE, and syringoma due to a lack of basaloid aggregates and only a small number of non-cyst-forming epithelial cells (Figure 4).

The Diagnosis: Microcystic Adnexal Carcinoma

Microcystic adnexal carcinoma (MAC) is a rare, low-grade adnexal carcinoma consisting of both ductal and pilar differentiation.¹ It typically presents in young to middle-aged adults as a flesh-colored or yellow indurated plaque on the upper lip, medial cheek, or chin. Histologically, MACs exhibit a biphasic pattern consisting of epithelial islands of cords and lumina creating tadpolelike ducts intermixed with basaloid nests (quiz image). Keratin horn cysts are common superficially. A dense red sclerotic stroma is seen interspersed between the ducts and epithelial islands creating a "paisley tie" appearance. The lesion displays an infiltrative pattern and can be deeply invasive, extending down to the fat and muscle (quiz image, inset). Perineural invasion is common. Atypia, when present, is minimal or mild and mitoses are rare. Although this tumor's histologic pattern appears aggressive in nature, it lacks immunohistochemical staining such as p53, Ki-67, bcl-2, and c-erbB-2 that correlate with malignant behavior.² A common diagnostic pitfall is examination of a superficial biopsy in which an MAC may be mistakenly identified as another entity.

Syringomas are benign adnexal neoplasms with ductal differentiation.³ They are more common in women, especially those of Asian descent, and in patients with Down syndrome. They typically present as multiple small, firm, flesh-colored papules in the periorbital area or upper trunk. Histologically, syringomas also display comma-shaped tubules and ducts with a tadpolelike appearance and a dense red stroma creating a paisley tie-like pattern. Ductal cells have an abundant pink cytoplasm. Syringomas are well-circumscribed and more superficial than MACs without an infiltrative pattern. They lack mitotic activity or perineural invasion (Figure 1).

Desmoplastic trichoepithelioma (DTE) is a benign follicular neoplasm.⁴ It presents in adulthood with a female predominance. Clinically, it appears as a solitary flesh-colored to yellow annular plaque with raised borders and a depressed central area, often on the medial cheek. Histologically, DTEs are well-circumscribed with narrow branching cords lined with polygonal cells. A dense red stroma in combination with the epithelioid aggregates also creates the paisley tie-like pattern in this lesion. Retraction between collagen bundles within the stroma can be seen, helping distinguish this lesion from a morpheaform basal cell carcinoma (BCC), which has retraction between the epithelium and stroma. Immunohistochemistry also can be a useful tool to help differentiate DTEs from morpheaform BCCs in that sparse cytokeratin 20-positive Merkel cells can be seen within the basaloid islands of DTE but not BCC.⁵ Also seen with DTEs are numerous keratin horn cysts that commonly are filled with dystrophic calcifications. Cellular atypia and mitoses are not seen (Figure 2). Compared to MACs, DTEs lack abundant ductal structures and also contain papillary mesenchymal bodies and a more fibroblast-rich stroma.

Morpheaform BCC is an aggressive subtype of BCC. It presents as a scarlike plaque that gradually expands. Thin infiltrating strands of basaloid cells are seen haphazardly throughout a pink sclerotic stroma. Tadpolelike basaloid islands and rarely horn cysts can be seen scattered superficially, creating the paisley tie-like pattern. This lesion is more infiltrating than a syringoma or a DTE, and perineural invasion is common. Retraction is uncommon, but when present, it is seen between the epithelial cords and adjacent stroma (Figure 3).

Trichoadenoma is another benign neoplasm of follicular differentiation.⁶ It typically presents as a dome-shaped papule or plaque on the head or neck. Histologically it displays numerous dilated cystic spaces that reflect its origin from isthmic and infundibular differentiation. There is no attachment to the overlying epidermis. It can be distinguished from MAC, DTE, and syringoma due to a lack of basaloid aggregates and only a small number of non-cyst-forming epithelial cells (Figure 4).

The Diagnosis: Microcystic Adnexal Carcinoma

Microcystic adnexal carcinoma (MAC) is a rare, low-grade adnexal carcinoma consisting of both ductal and pilar differentiation.¹ It typically presents in young to middle-aged adults as a flesh-colored or yellow indurated plaque on the upper lip, medial cheek, or chin. Histologically, MACs exhibit a biphasic pattern consisting of epithelial islands of cords and lumina creating tadpolelike ducts intermixed with basaloid nests (quiz image). Keratin horn cysts are common superficially. A dense red sclerotic stroma is seen interspersed between the ducts and epithelial islands creating a "paisley tie" appearance. The lesion displays an infiltrative pattern and can be deeply invasive, extending down to the fat and muscle (quiz image, inset). Perineural invasion is common. Atypia, when present, is minimal or mild and mitoses are rare. Although this tumor's histologic pattern appears aggressive in nature, it lacks immunohistochemical staining such as p53, Ki-67, bcl-2, and c-erbB-2 that correlate with malignant behavior.² A common diagnostic pitfall is examination of a superficial biopsy in which an MAC may be mistakenly identified as another entity.

Syringomas are benign adnexal neoplasms with ductal differentiation.³ They are more common in women, especially those of Asian descent, and in patients with Down syndrome. They typically present as multiple small, firm, flesh-colored papules in the periorbital area or upper trunk. Histologically, syringomas also display comma-shaped tubules and ducts with a tadpolelike appearance and a dense red stroma creating a paisley tie-like pattern. Ductal cells have an abundant pink cytoplasm. Syringomas are well-circumscribed and more superficial than MACs without an infiltrative pattern. They lack mitotic activity or perineural invasion (Figure 1).

Desmoplastic trichoepithelioma (DTE) is a benign follicular neoplasm.⁴ It presents in adulthood with a female predominance. Clinically, it appears as a solitary flesh-colored to yellow annular plaque with raised borders and a depressed central area, often on the medial cheek. Histologically, DTEs are well-circumscribed with narrow branching cords lined with polygonal cells. A dense red stroma in combination with the epithelioid aggregates also creates the paisley tie-like pattern in this lesion. Retraction between collagen bundles within the stroma can be seen, helping distinguish this lesion from a morpheaform basal cell carcinoma (BCC), which has retraction between the epithelium and stroma. Immunohistochemistry also can be a useful tool to help differentiate DTEs from morpheaform BCCs in that sparse cytokeratin 20-positive Merkel cells can be seen within the basaloid islands of DTE but not BCC.⁵ Also seen with DTEs are numerous keratin horn cysts that commonly are filled with dystrophic calcifications. Cellular atypia and mitoses are not seen (Figure 2). Compared to MACs, DTEs lack abundant ductal structures and also contain papillary mesenchymal bodies and a more fibroblast-rich stroma.

Morpheaform BCC is an aggressive subtype of BCC. It presents as a scarlike plaque that gradually expands. Thin infiltrating strands of basaloid cells are seen haphazardly throughout a pink sclerotic stroma. Tadpolelike basaloid islands and rarely horn cysts can be seen scattered superficially, creating the paisley tie-like pattern. This lesion is more infiltrating than a syringoma or a DTE, and perineural invasion is common. Retraction is uncommon, but when present, it is seen between the epithelial cords and adjacent stroma (Figure 3).

Trichoadenoma is another benign neoplasm of follicular differentiation.⁶ It typically presents as a dome-shaped papule or plaque on the head or neck. Histologically it displays numerous dilated cystic spaces that reflect its origin from isthmic and infundibular differentiation. There is no attachment to the overlying epidermis. It can be distinguished from MAC, DTE, and syringoma due to a lack of basaloid aggregates and only a small number of non-cyst-forming epithelial cells (Figure 4).

To the Editor:

The combination of menthol and methyl salicylate found in a variety of over-the-counter (OTC) creams in conjunction with a heat source such as a heating pad used for musculoskeletal symptoms can be a dire combination due to increased systemic absorption with associated toxicity and localized effects ranging from contact dermatitis or irritation to burn or necrosis.^1-6 We present a case of localized burn due a combination of topical methyl salicylate and heating pad use. We also discuss 2 commonly encountered side effects in the literature—localized burns and systemic toxicity associated with percutaneous absorption—and provide specific considerations related to the geriatric and pediatric populations.

A 62-year-old woman with a history of eczematous dermatitis and osteoarthritis with pain of the left shoulder presented to the dermatology clinic with painful skin-related changes on the left arm of 1 week’s duration. She was prescribed acetaminophen and ibuprofen. However, she self-medicated the left shoulder pain with 2 OTC products containing topical menthol and/or methyl salicylate in combination with a heating pad and likely fell asleep with this combination therapy applied. She noticed the burn the next morning. On examination, the left arm exhibited a geometric, irregularly shaped, erythematous, scaly plaque with a sharp transverse linear demarcation proximally and numerous erythematous linear scaly plaques oriented in an axial orientation with less-defined borders distally (Figure). The patient was diagnosed with burn secondary to combination of topical methyl salicylate and heating pad use. The patient was advised to discontinue the topical medication and to use caution with the heating pad in the future. She was prescribed pramoxine-hydrocortisone lotion to be applied to the affected area twice daily up to 5 days weekly until resolution. Subsequent evaluations revealed progressive improvement with only mild postinflammatory hyperpigmentation noted at 6 months after the burn.

The US Food and Drug Administration (FDA) released statements in 2012 regarding concern for burns related to use of OTC musculoskeletal pain relievers, with 43 cases of burns reported due to methyl salicylate and menthol from 2004 to 2010. Most of the second- and third-degree burns occurred following topical applications of products containing either menthol monotherapy or a combination of methyl salicylate and menthol.^1,2 In 2006, the FDA had already ordered 5 firms to stop compounding topical pain relief formulations containing these ingredients, with concerns that it puts patients at increased risk because the compounded formulations had not received FDA approval.³ Despite package warnings, patients may not be aware of the concerning side effects and risks associated with use of OTC creams, especially in combination with occlusion or heating pad use. Our case highlights the importance of ongoing patient education and physician counseling when encountering patients with arthritis or musculoskeletal pain who may often try various OTC self-treatments for pain relief.⁷

In 2012, the FDA reports stated that the cases of mild to serious burns were associated with methyl salicylate and menthol usage, in some cases 24 hours after first usage. Typically, these effects occur when concentrations are more than either 3% menthol alone or a combination of more than 3% menthol and more than 10% methyl salicylate.^1,2 In our case, the patient had been using 2 different OTC products that may have contained as much as 11% menthol and/or 30% methyl salicylate. Electronic resources are available that disclose safety instructions including not to occlude the site, not to use on wounds, and not to be used in conjunction with a heating pad.^8,9 Skin breakdown and vasodilation are more likely to occur in a setting of heat and occlusion, which allows for more absorption and localized side effects.^4,10 Localized reactions may range from contact dermatitis⁴ to muscle necrosis.⁵

The most noteworthy case of localized destruction described a 62-year-old man who had applied topical methyl salicylate and menthol to the forearms, calves, and thighs, then intermittently used a heating pad for 15 to 20 minutes (total duration).⁵ He subsequently developed erythema and numerous 7.62- to 10.16-cm bullae, which was thought to be consistent with contact dermatitis. Three days later, he was found to have full-thickness cutaneous, fascial, and muscle necrosis in a linear pattern. He was hospitalized for approximately 1 year and treated with extensive debridement and a skin graft. His serum creatinine level increased from 0.7 mg per 100 mL to 2.7 mg per 100 mL (reference range, 0.6–1.2 mg/dL) with evidence of toxic nephrosis and persistent interstitial nephritis, demonstrating the severity of localized destruction that may result when combining these products with direct heat and potential subsequent systemic consequences of this combination.⁵

The systemic absorption of OTC formulations also has been studied. Morra et al¹⁰ studied 12 volunteers (6 women, 6 men) who applied either 5 g of methyl salicylate ointment 12.5% twice daily for 4 days to an area on the thigh (approximately equal to 567 mg salicylate) or trolamine cream 10% twice for 1 day. The participants underwent a break for 7 days and then switched to the alternate treatment. They found that 0.31 to 0.91 mg/L methyl salicylate was detected in the serum 1 hour after applying the ointment consisting of methyl salicylate, and 2 to 6 mg/L methyl salicylate was detected on day 4. Therapeutic serum salicylate levels are 150 to 300 mg/L. They found that approximately 22% of the methyl salicylate also was found in urine samples on day 4. Although these figures may appear small, this study was prompted when a 62-year-old man presented to the emergency department with symptoms of salicylate toxicity and a serum concentration of 518 mg/L from twice-daily use of an OTC formulation containing methyl salicylate over the course of multiple weeks.¹⁰ Additionally, those who have aspirin hypersensitivity should be cautious when using such products due to the risk for reported angioedema.⁴

Providers must exercise extreme caution while caring for geriatric patients, especially if patients are taking warfarin. The combined effects of warfarin and methyl salicylate have previously caused cutaneous purpura, gastrointestinal bleeding, and elevated international normalized ratio values.^4,10 Older individuals also have increased skin fragility, allowing microtraumatic insult to easily develop. This fragility, along with an overall decreased intactness of the skin barrier, may lead to increased skin absorption. Furthermore, the addition of applying any heat source places the geriatric patient at greater risk for adverse events.¹⁰

In considering the limits of age, the pediatric population also has been studied regarding salicylate toxicity. Most commonly, oral ingestion has caused fatalities, as oil of wintergreen has been cited as extremely dangerous for children if swallowed; doses as small as a teaspoon (5 mL: 7000 mg salicylate) have resulted in fatalities.^4,6 Although the consumption of a large amount of a cream- or ointment-based product is unlikely due to the consistency of the medication,⁶ the thought does merit consideration in the inquisitive toddler age group. For a 15-kg toddler, 150 mg/kg of aspirin or 2250 mg of aspirin, is considered the toxic level, which upon conversion to methyl salicylate levels using a 1.4 factor equates to 1607 mg of methyl salicylate to reach toxicity.⁶ If using a product with methyl salicylate 30% composition, 1 g of the product contains 300 mg of methyl salicylate; therefore if the toddler consumed approximately 5.3 g of the product (1607 mg methyl salicylate [toxic level] divided by 300 mg methyl salicylate per 1 g of product), he/she would reach toxic levels.^6,11 To put this into perspective, a 2-oz tube contains 57 g (approximately 10 times the toxic dose) of the product.⁸ Thus, although there is less concern overall for consumption of cream- or ointment-based methyl salicylate, there still is potential for harm if a small child were to ingest such a product containing higher percentages of methyl salicylate.⁶

There also have been reports of pediatric toxicity related to percutaneous absorption, even leading to pediatric fatality.^4,6 In particular, there was a case of a young boy hospitalized with ichthyosis who received escalating doses of percutaneous salicylate, which resulted in toxicity; when therapy was discontinued, he experienced full recovery.¹² In 2007, a 17-year-old adolescent girl died from methyl salicylate toxicity after numerous applications of salicylate-containing products in conjunction with medicated pads.⁷

Although the FDA has drawn attention and encouraged caution with use of OTC topical musculoskeletal pain relievers, the importance of ensuring patients are fully aware of potential burns, permanent skin or muscle damage, and even death if used inappropriately cannot be overstated. The FDA consumer health information website has 2 patient-directed handouts^2,3 that may be useful to post in patient waiting areas to increase overall understanding of the risks associated with OTC products containing methyl salicylate and menthol ingredients. Fortunately, our patient suffered only mild postinflammatory hyperpigmentation without substantial sustained consequences.

To the Editor:

The combination of menthol and methyl salicylate found in a variety of over-the-counter (OTC) creams in conjunction with a heat source such as a heating pad used for musculoskeletal symptoms can be a dire combination due to increased systemic absorption with associated toxicity and localized effects ranging from contact dermatitis or irritation to burn or necrosis.^1-6 We present a case of localized burn due a combination of topical methyl salicylate and heating pad use. We also discuss 2 commonly encountered side effects in the literature—localized burns and systemic toxicity associated with percutaneous absorption—and provide specific considerations related to the geriatric and pediatric populations.

A 62-year-old woman with a history of eczematous dermatitis and osteoarthritis with pain of the left shoulder presented to the dermatology clinic with painful skin-related changes on the left arm of 1 week’s duration. She was prescribed acetaminophen and ibuprofen. However, she self-medicated the left shoulder pain with 2 OTC products containing topical menthol and/or methyl salicylate in combination with a heating pad and likely fell asleep with this combination therapy applied. She noticed the burn the next morning. On examination, the left arm exhibited a geometric, irregularly shaped, erythematous, scaly plaque with a sharp transverse linear demarcation proximally and numerous erythematous linear scaly plaques oriented in an axial orientation with less-defined borders distally (Figure). The patient was diagnosed with burn secondary to combination of topical methyl salicylate and heating pad use. The patient was advised to discontinue the topical medication and to use caution with the heating pad in the future. She was prescribed pramoxine-hydrocortisone lotion to be applied to the affected area twice daily up to 5 days weekly until resolution. Subsequent evaluations revealed progressive improvement with only mild postinflammatory hyperpigmentation noted at 6 months after the burn.

The US Food and Drug Administration (FDA) released statements in 2012 regarding concern for burns related to use of OTC musculoskeletal pain relievers, with 43 cases of burns reported due to methyl salicylate and menthol from 2004 to 2010. Most of the second- and third-degree burns occurred following topical applications of products containing either menthol monotherapy or a combination of methyl salicylate and menthol.^1,2 In 2006, the FDA had already ordered 5 firms to stop compounding topical pain relief formulations containing these ingredients, with concerns that it puts patients at increased risk because the compounded formulations had not received FDA approval.³ Despite package warnings, patients may not be aware of the concerning side effects and risks associated with use of OTC creams, especially in combination with occlusion or heating pad use. Our case highlights the importance of ongoing patient education and physician counseling when encountering patients with arthritis or musculoskeletal pain who may often try various OTC self-treatments for pain relief.⁷

In 2012, the FDA reports stated that the cases of mild to serious burns were associated with methyl salicylate and menthol usage, in some cases 24 hours after first usage. Typically, these effects occur when concentrations are more than either 3% menthol alone or a combination of more than 3% menthol and more than 10% methyl salicylate.^1,2 In our case, the patient had been using 2 different OTC products that may have contained as much as 11% menthol and/or 30% methyl salicylate. Electronic resources are available that disclose safety instructions including not to occlude the site, not to use on wounds, and not to be used in conjunction with a heating pad.^8,9 Skin breakdown and vasodilation are more likely to occur in a setting of heat and occlusion, which allows for more absorption and localized side effects.^4,10 Localized reactions may range from contact dermatitis⁴ to muscle necrosis.⁵

The most noteworthy case of localized destruction described a 62-year-old man who had applied topical methyl salicylate and menthol to the forearms, calves, and thighs, then intermittently used a heating pad for 15 to 20 minutes (total duration).⁵ He subsequently developed erythema and numerous 7.62- to 10.16-cm bullae, which was thought to be consistent with contact dermatitis. Three days later, he was found to have full-thickness cutaneous, fascial, and muscle necrosis in a linear pattern. He was hospitalized for approximately 1 year and treated with extensive debridement and a skin graft. His serum creatinine level increased from 0.7 mg per 100 mL to 2.7 mg per 100 mL (reference range, 0.6–1.2 mg/dL) with evidence of toxic nephrosis and persistent interstitial nephritis, demonstrating the severity of localized destruction that may result when combining these products with direct heat and potential subsequent systemic consequences of this combination.⁵

The systemic absorption of OTC formulations also has been studied. Morra et al¹⁰ studied 12 volunteers (6 women, 6 men) who applied either 5 g of methyl salicylate ointment 12.5% twice daily for 4 days to an area on the thigh (approximately equal to 567 mg salicylate) or trolamine cream 10% twice for 1 day. The participants underwent a break for 7 days and then switched to the alternate treatment. They found that 0.31 to 0.91 mg/L methyl salicylate was detected in the serum 1 hour after applying the ointment consisting of methyl salicylate, and 2 to 6 mg/L methyl salicylate was detected on day 4. Therapeutic serum salicylate levels are 150 to 300 mg/L. They found that approximately 22% of the methyl salicylate also was found in urine samples on day 4. Although these figures may appear small, this study was prompted when a 62-year-old man presented to the emergency department with symptoms of salicylate toxicity and a serum concentration of 518 mg/L from twice-daily use of an OTC formulation containing methyl salicylate over the course of multiple weeks.¹⁰ Additionally, those who have aspirin hypersensitivity should be cautious when using such products due to the risk for reported angioedema.⁴

Providers must exercise extreme caution while caring for geriatric patients, especially if patients are taking warfarin. The combined effects of warfarin and methyl salicylate have previously caused cutaneous purpura, gastrointestinal bleeding, and elevated international normalized ratio values.^4,10 Older individuals also have increased skin fragility, allowing microtraumatic insult to easily develop. This fragility, along with an overall decreased intactness of the skin barrier, may lead to increased skin absorption. Furthermore, the addition of applying any heat source places the geriatric patient at greater risk for adverse events.¹⁰

In considering the limits of age, the pediatric population also has been studied regarding salicylate toxicity. Most commonly, oral ingestion has caused fatalities, as oil of wintergreen has been cited as extremely dangerous for children if swallowed; doses as small as a teaspoon (5 mL: 7000 mg salicylate) have resulted in fatalities.^4,6 Although the consumption of a large amount of a cream- or ointment-based product is unlikely due to the consistency of the medication,⁶ the thought does merit consideration in the inquisitive toddler age group. For a 15-kg toddler, 150 mg/kg of aspirin or 2250 mg of aspirin, is considered the toxic level, which upon conversion to methyl salicylate levels using a 1.4 factor equates to 1607 mg of methyl salicylate to reach toxicity.⁶ If using a product with methyl salicylate 30% composition, 1 g of the product contains 300 mg of methyl salicylate; therefore if the toddler consumed approximately 5.3 g of the product (1607 mg methyl salicylate [toxic level] divided by 300 mg methyl salicylate per 1 g of product), he/she would reach toxic levels.^6,11 To put this into perspective, a 2-oz tube contains 57 g (approximately 10 times the toxic dose) of the product.⁸ Thus, although there is less concern overall for consumption of cream- or ointment-based methyl salicylate, there still is potential for harm if a small child were to ingest such a product containing higher percentages of methyl salicylate.⁶

There also have been reports of pediatric toxicity related to percutaneous absorption, even leading to pediatric fatality.^4,6 In particular, there was a case of a young boy hospitalized with ichthyosis who received escalating doses of percutaneous salicylate, which resulted in toxicity; when therapy was discontinued, he experienced full recovery.¹² In 2007, a 17-year-old adolescent girl died from methyl salicylate toxicity after numerous applications of salicylate-containing products in conjunction with medicated pads.⁷

Although the FDA has drawn attention and encouraged caution with use of OTC topical musculoskeletal pain relievers, the importance of ensuring patients are fully aware of potential burns, permanent skin or muscle damage, and even death if used inappropriately cannot be overstated. The FDA consumer health information website has 2 patient-directed handouts^2,3 that may be useful to post in patient waiting areas to increase overall understanding of the risks associated with OTC products containing methyl salicylate and menthol ingredients. Fortunately, our patient suffered only mild postinflammatory hyperpigmentation without substantial sustained consequences.

To the Editor:

The combination of menthol and methyl salicylate found in a variety of over-the-counter (OTC) creams in conjunction with a heat source such as a heating pad used for musculoskeletal symptoms can be a dire combination due to increased systemic absorption with associated toxicity and localized effects ranging from contact dermatitis or irritation to burn or necrosis.^1-6 We present a case of localized burn due a combination of topical methyl salicylate and heating pad use. We also discuss 2 commonly encountered side effects in the literature—localized burns and systemic toxicity associated with percutaneous absorption—and provide specific considerations related to the geriatric and pediatric populations.

A 62-year-old woman with a history of eczematous dermatitis and osteoarthritis with pain of the left shoulder presented to the dermatology clinic with painful skin-related changes on the left arm of 1 week’s duration. She was prescribed acetaminophen and ibuprofen. However, she self-medicated the left shoulder pain with 2 OTC products containing topical menthol and/or methyl salicylate in combination with a heating pad and likely fell asleep with this combination therapy applied. She noticed the burn the next morning. On examination, the left arm exhibited a geometric, irregularly shaped, erythematous, scaly plaque with a sharp transverse linear demarcation proximally and numerous erythematous linear scaly plaques oriented in an axial orientation with less-defined borders distally (Figure). The patient was diagnosed with burn secondary to combination of topical methyl salicylate and heating pad use. The patient was advised to discontinue the topical medication and to use caution with the heating pad in the future. She was prescribed pramoxine-hydrocortisone lotion to be applied to the affected area twice daily up to 5 days weekly until resolution. Subsequent evaluations revealed progressive improvement with only mild postinflammatory hyperpigmentation noted at 6 months after the burn.

The US Food and Drug Administration (FDA) released statements in 2012 regarding concern for burns related to use of OTC musculoskeletal pain relievers, with 43 cases of burns reported due to methyl salicylate and menthol from 2004 to 2010. Most of the second- and third-degree burns occurred following topical applications of products containing either menthol monotherapy or a combination of methyl salicylate and menthol.^1,2 In 2006, the FDA had already ordered 5 firms to stop compounding topical pain relief formulations containing these ingredients, with concerns that it puts patients at increased risk because the compounded formulations had not received FDA approval.³ Despite package warnings, patients may not be aware of the concerning side effects and risks associated with use of OTC creams, especially in combination with occlusion or heating pad use. Our case highlights the importance of ongoing patient education and physician counseling when encountering patients with arthritis or musculoskeletal pain who may often try various OTC self-treatments for pain relief.⁷

In 2012, the FDA reports stated that the cases of mild to serious burns were associated with methyl salicylate and menthol usage, in some cases 24 hours after first usage. Typically, these effects occur when concentrations are more than either 3% menthol alone or a combination of more than 3% menthol and more than 10% methyl salicylate.^1,2 In our case, the patient had been using 2 different OTC products that may have contained as much as 11% menthol and/or 30% methyl salicylate. Electronic resources are available that disclose safety instructions including not to occlude the site, not to use on wounds, and not to be used in conjunction with a heating pad.^8,9 Skin breakdown and vasodilation are more likely to occur in a setting of heat and occlusion, which allows for more absorption and localized side effects.^4,10 Localized reactions may range from contact dermatitis⁴ to muscle necrosis.⁵

The most noteworthy case of localized destruction described a 62-year-old man who had applied topical methyl salicylate and menthol to the forearms, calves, and thighs, then intermittently used a heating pad for 15 to 20 minutes (total duration).⁵ He subsequently developed erythema and numerous 7.62- to 10.16-cm bullae, which was thought to be consistent with contact dermatitis. Three days later, he was found to have full-thickness cutaneous, fascial, and muscle necrosis in a linear pattern. He was hospitalized for approximately 1 year and treated with extensive debridement and a skin graft. His serum creatinine level increased from 0.7 mg per 100 mL to 2.7 mg per 100 mL (reference range, 0.6–1.2 mg/dL) with evidence of toxic nephrosis and persistent interstitial nephritis, demonstrating the severity of localized destruction that may result when combining these products with direct heat and potential subsequent systemic consequences of this combination.⁵

The systemic absorption of OTC formulations also has been studied. Morra et al¹⁰ studied 12 volunteers (6 women, 6 men) who applied either 5 g of methyl salicylate ointment 12.5% twice daily for 4 days to an area on the thigh (approximately equal to 567 mg salicylate) or trolamine cream 10% twice for 1 day. The participants underwent a break for 7 days and then switched to the alternate treatment. They found that 0.31 to 0.91 mg/L methyl salicylate was detected in the serum 1 hour after applying the ointment consisting of methyl salicylate, and 2 to 6 mg/L methyl salicylate was detected on day 4. Therapeutic serum salicylate levels are 150 to 300 mg/L. They found that approximately 22% of the methyl salicylate also was found in urine samples on day 4. Although these figures may appear small, this study was prompted when a 62-year-old man presented to the emergency department with symptoms of salicylate toxicity and a serum concentration of 518 mg/L from twice-daily use of an OTC formulation containing methyl salicylate over the course of multiple weeks.¹⁰ Additionally, those who have aspirin hypersensitivity should be cautious when using such products due to the risk for reported angioedema.⁴

Providers must exercise extreme caution while caring for geriatric patients, especially if patients are taking warfarin. The combined effects of warfarin and methyl salicylate have previously caused cutaneous purpura, gastrointestinal bleeding, and elevated international normalized ratio values.^4,10 Older individuals also have increased skin fragility, allowing microtraumatic insult to easily develop. This fragility, along with an overall decreased intactness of the skin barrier, may lead to increased skin absorption. Furthermore, the addition of applying any heat source places the geriatric patient at greater risk for adverse events.¹⁰

In considering the limits of age, the pediatric population also has been studied regarding salicylate toxicity. Most commonly, oral ingestion has caused fatalities, as oil of wintergreen has been cited as extremely dangerous for children if swallowed; doses as small as a teaspoon (5 mL: 7000 mg salicylate) have resulted in fatalities.^4,6 Although the consumption of a large amount of a cream- or ointment-based product is unlikely due to the consistency of the medication,⁶ the thought does merit consideration in the inquisitive toddler age group. For a 15-kg toddler, 150 mg/kg of aspirin or 2250 mg of aspirin, is considered the toxic level, which upon conversion to methyl salicylate levels using a 1.4 factor equates to 1607 mg of methyl salicylate to reach toxicity.⁶ If using a product with methyl salicylate 30% composition, 1 g of the product contains 300 mg of methyl salicylate; therefore if the toddler consumed approximately 5.3 g of the product (1607 mg methyl salicylate [toxic level] divided by 300 mg methyl salicylate per 1 g of product), he/she would reach toxic levels.^6,11 To put this into perspective, a 2-oz tube contains 57 g (approximately 10 times the toxic dose) of the product.⁸ Thus, although there is less concern overall for consumption of cream- or ointment-based methyl salicylate, there still is potential for harm if a small child were to ingest such a product containing higher percentages of methyl salicylate.⁶

There also have been reports of pediatric toxicity related to percutaneous absorption, even leading to pediatric fatality.^4,6 In particular, there was a case of a young boy hospitalized with ichthyosis who received escalating doses of percutaneous salicylate, which resulted in toxicity; when therapy was discontinued, he experienced full recovery.¹² In 2007, a 17-year-old adolescent girl died from methyl salicylate toxicity after numerous applications of salicylate-containing products in conjunction with medicated pads.⁷

Although the FDA has drawn attention and encouraged caution with use of OTC topical musculoskeletal pain relievers, the importance of ensuring patients are fully aware of potential burns, permanent skin or muscle damage, and even death if used inappropriately cannot be overstated. The FDA consumer health information website has 2 patient-directed handouts^2,3 that may be useful to post in patient waiting areas to increase overall understanding of the risks associated with OTC products containing methyl salicylate and menthol ingredients. Fortunately, our patient suffered only mild postinflammatory hyperpigmentation without substantial sustained consequences.