Acne

Isotretinoin is the most effective treatment of recalcitrant acne, but because of its teratogenicity and potential association with psychiatric adverse effects, it has been heavily regulated by the US Food and Drug Administration (FDA) through the iPLEDGE program since 2006.^1,2 To manage the risk of teratogenicity associated with isotretinoin, various pregnancy prevention programs have been developed, but none of these programs have demonstrated a zero fetal exposure rate. The FDA reported 122 isotretinoin-exposed pregnancies during the first year iPLEDGE was implemented, which was a slight increase from the 120 pregnancies reported the year after the implementation of the System to Manage Accutane-Related Teratogenicity program, iPLEDGE’s predecessor.³ The iPLEDGE program requires registration of all wholesalers distributing isotretinoin, all health care providers prescribing isotretinoin, all pharmacies dispensing isotretinoin, and all female and male patients prescribed isotretinoin to create a verifiable link that only enables patients who have met all criteria to pick up their prescriptions. For patients of reproductive potential, there are additional qualification criteria and monthly requirements; before receiving their prescription every month, patients of reproductive potential must undergo a urine or serum pregnancy test with negative results, and patients must be counseled by prescribers regarding the risks of the drug and verify they are using 2 methods of contraception (or practicing abstinence) each month before completing online questions that test their understanding of the drug’s side effects and their chosen methods of contraception.⁴ These requirements place burdens on both patients and prescribers. Studies have shown that in the 2 years after the implementation of iPLEDGE, there was a 29% decrease in isotretinoin prescriptions.^1-3

We conducted a survey study to see if clinicians chose not to prescribe isotretinoin to appropriate candidates specifically because of the administrative burden of iPLEDGE. Secondarily, we investigated the medications these clinicians would prescribe instead of isotretinoin.

Methods

In March 2020, we administered an anonymous online survey consisting of 12 multiple-choice questions to verified board-certified dermatologists in the United States using a social media group. The University of Rochester’s (Rochester, New York) institutional review board determined that our protocol met criteria for exemption (IRB STUDY00004693).

Statistical Analysis—Primary analyses used Pearson χ² tests to identify significant differences among respondent groups, practice settings, age of respondents, and time spent registering patients for iPLEDGE.

Results

Survey results from 510 respondents are summarized in the Table.

Burden of iPLEDGE—Of the respondents, 336 (65.9%) were frequent prescribers of isotretinoin, 166 (32.5%) were infrequent prescribers, and 8 (1.6%) were never prescribers. Significantly more isotretinoin prescribers estimated that their offices spend 16 to 30 minutes registering a new isotretinoin patient with the iPLEDGE program (289 [57.6%]) compared with 0 to 15 minutes (140 [27.9%]), 31 to 45 minutes (57 [11.3%]), and morethan 45 minutes (16 [3.2%])(χ²₃=22.09, P<.0001). Furthermore, 150 dermatologists reported sometimes not prescribing, and 2 reported never prescribing isotretinoin because of the burden of iPLEDGE.

Systemic Agents Prescribed Instead of Isotretinoin—Of the respondents, 73.0% (n=111) prescribed spironolactone to female patients and 88.8% (n=135) prescribed oral antibiotics to male patients instead of isotretinoin. Spironolactone typically is not prescribed to male patients with acne because of its feminizing side effects, such as gynecomastia.⁵ According to the American Academy of Dermatology guidelines on acne, systemic antibiotic usage should be limited to the shortest possible duration (ie, less than 3–4 months) because of potential bacterial resistance and reported associations with inflammatory bowel disease, Clostridium difficile infection, and candidiasis.^6,7

Prescriber Demographics—The frequency of not prescribing isotretinoin did not vary by practice setting (χ ²₄=6.44, P=.1689) but did vary by age of the dermatologist (χ²₃=15.57, P=.0014). Dermatologists younger than 46 years were more likely (Figure) to report not prescribing isotretinoin because of the administrative burden of iPLEDGE. We speculate that this is because younger dermatologists are less established in their practices and therefore may have less support to complete registration without interruption of clinic workflow.

Comment

The results of our survey suggest that the administrative burden of iPLEDGE may be compelling prescribers to refrain from prescribing isotretinoin therapy to appropriate candidates when it would otherwise be the drug of choice.

Recent Changes to iPLEDGE—The FDA recently approved a modification to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program based on the advocacy efforts from the American Academy of Dermatology. Starting December 13, 2021, the 3 patient risk categories were consolidated into 2 gender-neutral categories: patients who can get pregnant and patients who cannot get pregnant.⁸ The iPLEDGE website was transitioned to a new system, and all iPLEDGE REMS users had to update their iPLEDGE accounts. After the implementation of the modified program, user access issues arose, leading to delayed treatment when patients, providers, and pharmacists were all locked out of the online system; users also experienced long hold times with the call center.⁸ This change highlights the ongoing critical need for a streamlined program that increases patient access to isotretinoin while maintaining safety.

Study Limitations—The main limitation of this study was the inability to calculate a true response rate to our survey. We distributed the survey via social media to maintain anonymity of the respondents. We could not track how many saw the link to compare with the number of respondents. Therefore, the only way we could calculate a response rate was with the total number of members in the group, which fluctuated around 4000 at the time we administered the survey. We calculated that we would need at least 351 responses to have a 5% margin of error at 95% confidence for our results to be generalizable and significant. We ultimately received 510 responses, which gave us a 4.05% margin of error at 95% confidence and an estimated 12.7% response rate. Since some members of the group are not active and did not see the survey link, our true response rate was likely higher. Therefore, we concluded that the survey was successful, and our significant responses were representative of US dermatologists.

Suggestions to Improve iPLEDGE Process—Our survey study should facilitate further discussions on the importance of simplifying iPLEDGE. One suggestion for improving iPLEDGE is to remove the initial registration month so care is not delayed. Currently, a patient who can get pregnant must be on 2 forms of contraception for 30 days after they register as a patient before they are eligible to fill their prescription.⁴ This process is unnecessarily long and arduous and could be eliminated as long as the patient has already been on an effective form of contraception and has a negative pregnancy test on the day of registration. The need to repeat contraception comprehension questions monthly is redundant and also could be removed. Another suggestion is to remove the category of patients who cannot become pregnant from the system entirely. Isotretinoin does not appear to be associated with adverse psychiatric effects as shown through the systematic review and meta-analysis of numerous studies.⁹ If anything, the treatment of acne with isotretinoin appears to mitigate depressive symptoms. The iPLEDGE program does not manage this largely debunked idea. Because the program’s sole goal is to manage the risk of isotretinoin’s teratogenicity, the category of those who cannot become pregnant should not be included.

Conclusion

This survey highlights the burdens of iPLEDGE for dermatologists and the need for a more streamlined risk management program. The burden was felt equally among all practice types but especially by younger dermatologists (<46 years). This time-consuming program is deterring some dermatologists from prescribing isotretinoin and ultimately limiting patient access to an effective medication.

Acknowledgment—The authors thank all of the responding clinicians who provided insight into the impact of iPLEDGE on their isotretinoin prescribing patterns.

Isotretinoin is the most effective treatment of recalcitrant acne, but because of its teratogenicity and potential association with psychiatric adverse effects, it has been heavily regulated by the US Food and Drug Administration (FDA) through the iPLEDGE program since 2006.^1,2 To manage the risk of teratogenicity associated with isotretinoin, various pregnancy prevention programs have been developed, but none of these programs have demonstrated a zero fetal exposure rate. The FDA reported 122 isotretinoin-exposed pregnancies during the first year iPLEDGE was implemented, which was a slight increase from the 120 pregnancies reported the year after the implementation of the System to Manage Accutane-Related Teratogenicity program, iPLEDGE’s predecessor.³ The iPLEDGE program requires registration of all wholesalers distributing isotretinoin, all health care providers prescribing isotretinoin, all pharmacies dispensing isotretinoin, and all female and male patients prescribed isotretinoin to create a verifiable link that only enables patients who have met all criteria to pick up their prescriptions. For patients of reproductive potential, there are additional qualification criteria and monthly requirements; before receiving their prescription every month, patients of reproductive potential must undergo a urine or serum pregnancy test with negative results, and patients must be counseled by prescribers regarding the risks of the drug and verify they are using 2 methods of contraception (or practicing abstinence) each month before completing online questions that test their understanding of the drug’s side effects and their chosen methods of contraception.⁴ These requirements place burdens on both patients and prescribers. Studies have shown that in the 2 years after the implementation of iPLEDGE, there was a 29% decrease in isotretinoin prescriptions.^1-3

We conducted a survey study to see if clinicians chose not to prescribe isotretinoin to appropriate candidates specifically because of the administrative burden of iPLEDGE. Secondarily, we investigated the medications these clinicians would prescribe instead of isotretinoin.

Methods

In March 2020, we administered an anonymous online survey consisting of 12 multiple-choice questions to verified board-certified dermatologists in the United States using a social media group. The University of Rochester’s (Rochester, New York) institutional review board determined that our protocol met criteria for exemption (IRB STUDY00004693).

Statistical Analysis—Primary analyses used Pearson χ² tests to identify significant differences among respondent groups, practice settings, age of respondents, and time spent registering patients for iPLEDGE.

Results

Survey results from 510 respondents are summarized in the Table.

Burden of iPLEDGE—Of the respondents, 336 (65.9%) were frequent prescribers of isotretinoin, 166 (32.5%) were infrequent prescribers, and 8 (1.6%) were never prescribers. Significantly more isotretinoin prescribers estimated that their offices spend 16 to 30 minutes registering a new isotretinoin patient with the iPLEDGE program (289 [57.6%]) compared with 0 to 15 minutes (140 [27.9%]), 31 to 45 minutes (57 [11.3%]), and morethan 45 minutes (16 [3.2%])(χ²₃=22.09, P<.0001). Furthermore, 150 dermatologists reported sometimes not prescribing, and 2 reported never prescribing isotretinoin because of the burden of iPLEDGE.

Systemic Agents Prescribed Instead of Isotretinoin—Of the respondents, 73.0% (n=111) prescribed spironolactone to female patients and 88.8% (n=135) prescribed oral antibiotics to male patients instead of isotretinoin. Spironolactone typically is not prescribed to male patients with acne because of its feminizing side effects, such as gynecomastia.⁵ According to the American Academy of Dermatology guidelines on acne, systemic antibiotic usage should be limited to the shortest possible duration (ie, less than 3–4 months) because of potential bacterial resistance and reported associations with inflammatory bowel disease, Clostridium difficile infection, and candidiasis.^6,7

Prescriber Demographics—The frequency of not prescribing isotretinoin did not vary by practice setting (χ ²₄=6.44, P=.1689) but did vary by age of the dermatologist (χ²₃=15.57, P=.0014). Dermatologists younger than 46 years were more likely (Figure) to report not prescribing isotretinoin because of the administrative burden of iPLEDGE. We speculate that this is because younger dermatologists are less established in their practices and therefore may have less support to complete registration without interruption of clinic workflow.

Comment

The results of our survey suggest that the administrative burden of iPLEDGE may be compelling prescribers to refrain from prescribing isotretinoin therapy to appropriate candidates when it would otherwise be the drug of choice.

Recent Changes to iPLEDGE—The FDA recently approved a modification to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program based on the advocacy efforts from the American Academy of Dermatology. Starting December 13, 2021, the 3 patient risk categories were consolidated into 2 gender-neutral categories: patients who can get pregnant and patients who cannot get pregnant.⁸ The iPLEDGE website was transitioned to a new system, and all iPLEDGE REMS users had to update their iPLEDGE accounts. After the implementation of the modified program, user access issues arose, leading to delayed treatment when patients, providers, and pharmacists were all locked out of the online system; users also experienced long hold times with the call center.⁸ This change highlights the ongoing critical need for a streamlined program that increases patient access to isotretinoin while maintaining safety.

Study Limitations—The main limitation of this study was the inability to calculate a true response rate to our survey. We distributed the survey via social media to maintain anonymity of the respondents. We could not track how many saw the link to compare with the number of respondents. Therefore, the only way we could calculate a response rate was with the total number of members in the group, which fluctuated around 4000 at the time we administered the survey. We calculated that we would need at least 351 responses to have a 5% margin of error at 95% confidence for our results to be generalizable and significant. We ultimately received 510 responses, which gave us a 4.05% margin of error at 95% confidence and an estimated 12.7% response rate. Since some members of the group are not active and did not see the survey link, our true response rate was likely higher. Therefore, we concluded that the survey was successful, and our significant responses were representative of US dermatologists.

Suggestions to Improve iPLEDGE Process—Our survey study should facilitate further discussions on the importance of simplifying iPLEDGE. One suggestion for improving iPLEDGE is to remove the initial registration month so care is not delayed. Currently, a patient who can get pregnant must be on 2 forms of contraception for 30 days after they register as a patient before they are eligible to fill their prescription.⁴ This process is unnecessarily long and arduous and could be eliminated as long as the patient has already been on an effective form of contraception and has a negative pregnancy test on the day of registration. The need to repeat contraception comprehension questions monthly is redundant and also could be removed. Another suggestion is to remove the category of patients who cannot become pregnant from the system entirely. Isotretinoin does not appear to be associated with adverse psychiatric effects as shown through the systematic review and meta-analysis of numerous studies.⁹ If anything, the treatment of acne with isotretinoin appears to mitigate depressive symptoms. The iPLEDGE program does not manage this largely debunked idea. Because the program’s sole goal is to manage the risk of isotretinoin’s teratogenicity, the category of those who cannot become pregnant should not be included.

Conclusion

This survey highlights the burdens of iPLEDGE for dermatologists and the need for a more streamlined risk management program. The burden was felt equally among all practice types but especially by younger dermatologists (<46 years). This time-consuming program is deterring some dermatologists from prescribing isotretinoin and ultimately limiting patient access to an effective medication.

Acknowledgment—The authors thank all of the responding clinicians who provided insight into the impact of iPLEDGE on their isotretinoin prescribing patterns.

Isotretinoin is the most effective treatment of recalcitrant acne, but because of its teratogenicity and potential association with psychiatric adverse effects, it has been heavily regulated by the US Food and Drug Administration (FDA) through the iPLEDGE program since 2006.^1,2 To manage the risk of teratogenicity associated with isotretinoin, various pregnancy prevention programs have been developed, but none of these programs have demonstrated a zero fetal exposure rate. The FDA reported 122 isotretinoin-exposed pregnancies during the first year iPLEDGE was implemented, which was a slight increase from the 120 pregnancies reported the year after the implementation of the System to Manage Accutane-Related Teratogenicity program, iPLEDGE’s predecessor.³ The iPLEDGE program requires registration of all wholesalers distributing isotretinoin, all health care providers prescribing isotretinoin, all pharmacies dispensing isotretinoin, and all female and male patients prescribed isotretinoin to create a verifiable link that only enables patients who have met all criteria to pick up their prescriptions. For patients of reproductive potential, there are additional qualification criteria and monthly requirements; before receiving their prescription every month, patients of reproductive potential must undergo a urine or serum pregnancy test with negative results, and patients must be counseled by prescribers regarding the risks of the drug and verify they are using 2 methods of contraception (or practicing abstinence) each month before completing online questions that test their understanding of the drug’s side effects and their chosen methods of contraception.⁴ These requirements place burdens on both patients and prescribers. Studies have shown that in the 2 years after the implementation of iPLEDGE, there was a 29% decrease in isotretinoin prescriptions.^1-3

We conducted a survey study to see if clinicians chose not to prescribe isotretinoin to appropriate candidates specifically because of the administrative burden of iPLEDGE. Secondarily, we investigated the medications these clinicians would prescribe instead of isotretinoin.

Methods

In March 2020, we administered an anonymous online survey consisting of 12 multiple-choice questions to verified board-certified dermatologists in the United States using a social media group. The University of Rochester’s (Rochester, New York) institutional review board determined that our protocol met criteria for exemption (IRB STUDY00004693).

Statistical Analysis—Primary analyses used Pearson χ² tests to identify significant differences among respondent groups, practice settings, age of respondents, and time spent registering patients for iPLEDGE.

Results

Survey results from 510 respondents are summarized in the Table.

Burden of iPLEDGE—Of the respondents, 336 (65.9%) were frequent prescribers of isotretinoin, 166 (32.5%) were infrequent prescribers, and 8 (1.6%) were never prescribers. Significantly more isotretinoin prescribers estimated that their offices spend 16 to 30 minutes registering a new isotretinoin patient with the iPLEDGE program (289 [57.6%]) compared with 0 to 15 minutes (140 [27.9%]), 31 to 45 minutes (57 [11.3%]), and morethan 45 minutes (16 [3.2%])(χ²₃=22.09, P<.0001). Furthermore, 150 dermatologists reported sometimes not prescribing, and 2 reported never prescribing isotretinoin because of the burden of iPLEDGE.

Systemic Agents Prescribed Instead of Isotretinoin—Of the respondents, 73.0% (n=111) prescribed spironolactone to female patients and 88.8% (n=135) prescribed oral antibiotics to male patients instead of isotretinoin. Spironolactone typically is not prescribed to male patients with acne because of its feminizing side effects, such as gynecomastia.⁵ According to the American Academy of Dermatology guidelines on acne, systemic antibiotic usage should be limited to the shortest possible duration (ie, less than 3–4 months) because of potential bacterial resistance and reported associations with inflammatory bowel disease, Clostridium difficile infection, and candidiasis.^6,7

Prescriber Demographics—The frequency of not prescribing isotretinoin did not vary by practice setting (χ ²₄=6.44, P=.1689) but did vary by age of the dermatologist (χ²₃=15.57, P=.0014). Dermatologists younger than 46 years were more likely (Figure) to report not prescribing isotretinoin because of the administrative burden of iPLEDGE. We speculate that this is because younger dermatologists are less established in their practices and therefore may have less support to complete registration without interruption of clinic workflow.

Comment

The results of our survey suggest that the administrative burden of iPLEDGE may be compelling prescribers to refrain from prescribing isotretinoin therapy to appropriate candidates when it would otherwise be the drug of choice.

Recent Changes to iPLEDGE—The FDA recently approved a modification to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program based on the advocacy efforts from the American Academy of Dermatology. Starting December 13, 2021, the 3 patient risk categories were consolidated into 2 gender-neutral categories: patients who can get pregnant and patients who cannot get pregnant.⁸ The iPLEDGE website was transitioned to a new system, and all iPLEDGE REMS users had to update their iPLEDGE accounts. After the implementation of the modified program, user access issues arose, leading to delayed treatment when patients, providers, and pharmacists were all locked out of the online system; users also experienced long hold times with the call center.⁸ This change highlights the ongoing critical need for a streamlined program that increases patient access to isotretinoin while maintaining safety.

Study Limitations—The main limitation of this study was the inability to calculate a true response rate to our survey. We distributed the survey via social media to maintain anonymity of the respondents. We could not track how many saw the link to compare with the number of respondents. Therefore, the only way we could calculate a response rate was with the total number of members in the group, which fluctuated around 4000 at the time we administered the survey. We calculated that we would need at least 351 responses to have a 5% margin of error at 95% confidence for our results to be generalizable and significant. We ultimately received 510 responses, which gave us a 4.05% margin of error at 95% confidence and an estimated 12.7% response rate. Since some members of the group are not active and did not see the survey link, our true response rate was likely higher. Therefore, we concluded that the survey was successful, and our significant responses were representative of US dermatologists.

Suggestions to Improve iPLEDGE Process—Our survey study should facilitate further discussions on the importance of simplifying iPLEDGE. One suggestion for improving iPLEDGE is to remove the initial registration month so care is not delayed. Currently, a patient who can get pregnant must be on 2 forms of contraception for 30 days after they register as a patient before they are eligible to fill their prescription.⁴ This process is unnecessarily long and arduous and could be eliminated as long as the patient has already been on an effective form of contraception and has a negative pregnancy test on the day of registration. The need to repeat contraception comprehension questions monthly is redundant and also could be removed. Another suggestion is to remove the category of patients who cannot become pregnant from the system entirely. Isotretinoin does not appear to be associated with adverse psychiatric effects as shown through the systematic review and meta-analysis of numerous studies.⁹ If anything, the treatment of acne with isotretinoin appears to mitigate depressive symptoms. The iPLEDGE program does not manage this largely debunked idea. Because the program’s sole goal is to manage the risk of isotretinoin’s teratogenicity, the category of those who cannot become pregnant should not be included.

Conclusion

This survey highlights the burdens of iPLEDGE for dermatologists and the need for a more streamlined risk management program. The burden was felt equally among all practice types but especially by younger dermatologists (<46 years). This time-consuming program is deterring some dermatologists from prescribing isotretinoin and ultimately limiting patient access to an effective medication.

Acknowledgment—The authors thank all of the responding clinicians who provided insight into the impact of iPLEDGE on their isotretinoin prescribing patterns.

Since 1950, the terms “diet and skin” in the medical literature have markedly increased, said Vivian Shi, MD associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock, who talked about nutritional approaches for select skin diseases at MedscapeLive’s Women’s and Pediatric Dermatology Seminar.

Myths abound, but some associations of diet with skin diseases hold water, and diet tweaks could supplement treatments and improve results in patients with acne, hidradenitis suppurativa (HS), and rosacea, she said.
 

Acne

What’s known, Dr. Shi said, is that the prevalence of acne is substantially lower in non-Westernized countries, and that diets in those countries generally have a low glycemic load, which decreases IGF-1 insulinlike growth factor 1 (IGF-1) concentrations, an accepted risk factor for acne. The Western diet also includes the hormonal effects of cow’s milk products.

Whey protein, which is popular as a supplement, isn’t good for acne, Dr. Shi said. It takes a couple of hours to digest, while casein protein digests more slowly, over 5-7 hours. If casein protein isn’t acceptable, good alternatives to whey protein are hemp seed, plant protein blends (peas, seeds, berries), egg white, brown rice isolate, and soy isolate protein.

Dairy products increase IGF-1 levels, hormonal mediators that can make acne worse. In addition, industrial cow’s milk can contain anabolic steroids and growth factor, leading to sebogenesis, Dr. Shi said. As for the type of milk, skim milk tends to be the most acnegenic and associated with the highest blood levels of IGF-1.

Supplementing with omega-3 fatty acids and gamma-linolenic acid improved mild to moderate acne in a double-blind, controlled study. Researchers randomized 45 patients with mild to moderate acne to an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a gamma-linolenic acid group (borage oil with 400 mg gamma-linolenic acid) or a control group. After 10 weeks in both treatment groups, there was a significant reduction in inflammatory and noninflammatory lesions.

Those with acne are more likely to be deficient in Vitamin D, research suggests. Researchers also found that among those who had vitamin D deficiency, supplementing with 1,000 IU daily for 2 months reduced inflammatory lesions by 35% after 8 weeks, compared with a 6% reduction in the control group.

Other research has found that those with a low serum zinc level had more severe acne and that 30-200 mg of zinc orally for 2-4 months reduced inflammatory acne. However, Dr. Shi cautioned that those taking zinc for more than 2 months also need a copper supplement, as zinc reduces the amount of copper absorbed by the body.

Dr. Shi’s “do’s” diet list for acne patients is a follows: Paleolithic and Mediterranean diets, omega-3 fatty acids, gamma-linolenic acids, Vitamin D, zinc, tubers, legumes, vegetables, fruits, and fish.

Unknowns, she said, include chocolate, caffeine, green tea, and high salt.
 

Hidradenitis suppurativa

Patents with HS who follow a Mediterranean diet most closely have less severe disease, research has found. In this study, those patients with HS with the lowest adherence had a Sartorius HS score of 59.38, while those who followed it the most closely had a score of 39 (of 80).

In another study, patients with HS reported the following foods as exacerbating HS: sweets, bread/pasta/rice, dairy, and high-fat foods. Alleviating foods included vegetables, fruit, chicken, and fish.

Dr. Shi’s dietary recommendations for patients with HS: Follow a Mediterranean diet, avoid high fat foods and highly processed foods, and focus on eating more vegetables, fresh fruit, corn-based cereal, white meat, and fish.

A retrospective study of patients with Hurley stage 1 and 2 found that oral zinc gluconate, 90 mg a day, combined with 2% topical triclosan twice a day, resulted in significantly decreased HS scores and nodules and improved quality of life after 3 months. Expect vitamin D deficiency, she added.

Lastly, Dr. Shi recommended, if necessary, “weight loss to reduce the inflammatory burden.”
 

Rosacea

Dietary triggers for rosacea are thought to include high-fat foods, dairy foods, spicy foods, hot drinks, cinnamon, and vanilla.

A population-based case-control study in China, which evaluated 1,347 rosacea patients and 1,290 healthy controls, found that a high intake of fatty foods positively correlated with erythematotelangiectatic rosacea (ETR) and phymatous rosacea. High-frequency dairy intake negatively correlated with ETR and papulopustular rosacea, which was a surprise, she said. And in this study, no significant correlations were found between sweets, coffee, and spicy foods. That goes against the traditional thinking, she said, but this was a Chinese cohort and their diet is probably vastly different than those in the United States.

Other rosacea triggers, Dr. Shi said, are niacin-containing foods such as turkey, chicken breast, crustaceans, dried Shiitake mushrooms, peanuts, tuna, and liver, as well as cold drinks, and formalin-containing foods (fish, squid, tofu, wet noodles).

As the field of nutrigenics – how genes affect how the body responds to food – evolves, more answers about the impact of diet on these diseases will be forthcoming, Dr. Shi said.

In an interactive panel discussion, she was asked if she talks about diet with all her patients with acne, rosacea, and HS, or just those not responding to traditional therapy.

“I think it’s an important conversation to have,” Dr. Shi responded. “When I’m done with the medication [instructions], I say: ‘There is something else you can do to augment what I just told you.’ ” That’s when she explains the dietary information. She also has a handout on diet and routinely refers patients for dietary counseling.

MedscapeLive and this news organization are owned by the same parent company. Dr. Shi disclosed consulting, investigative and research funding from several sources, but not directly related to the content of her talk.

Since 1950, the terms “diet and skin” in the medical literature have markedly increased, said Vivian Shi, MD associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock, who talked about nutritional approaches for select skin diseases at MedscapeLive’s Women’s and Pediatric Dermatology Seminar.

Myths abound, but some associations of diet with skin diseases hold water, and diet tweaks could supplement treatments and improve results in patients with acne, hidradenitis suppurativa (HS), and rosacea, she said.
 

Acne

What’s known, Dr. Shi said, is that the prevalence of acne is substantially lower in non-Westernized countries, and that diets in those countries generally have a low glycemic load, which decreases IGF-1 insulinlike growth factor 1 (IGF-1) concentrations, an accepted risk factor for acne. The Western diet also includes the hormonal effects of cow’s milk products.

Whey protein, which is popular as a supplement, isn’t good for acne, Dr. Shi said. It takes a couple of hours to digest, while casein protein digests more slowly, over 5-7 hours. If casein protein isn’t acceptable, good alternatives to whey protein are hemp seed, plant protein blends (peas, seeds, berries), egg white, brown rice isolate, and soy isolate protein.

Dairy products increase IGF-1 levels, hormonal mediators that can make acne worse. In addition, industrial cow’s milk can contain anabolic steroids and growth factor, leading to sebogenesis, Dr. Shi said. As for the type of milk, skim milk tends to be the most acnegenic and associated with the highest blood levels of IGF-1.

Supplementing with omega-3 fatty acids and gamma-linolenic acid improved mild to moderate acne in a double-blind, controlled study. Researchers randomized 45 patients with mild to moderate acne to an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a gamma-linolenic acid group (borage oil with 400 mg gamma-linolenic acid) or a control group. After 10 weeks in both treatment groups, there was a significant reduction in inflammatory and noninflammatory lesions.

Those with acne are more likely to be deficient in Vitamin D, research suggests. Researchers also found that among those who had vitamin D deficiency, supplementing with 1,000 IU daily for 2 months reduced inflammatory lesions by 35% after 8 weeks, compared with a 6% reduction in the control group.

Other research has found that those with a low serum zinc level had more severe acne and that 30-200 mg of zinc orally for 2-4 months reduced inflammatory acne. However, Dr. Shi cautioned that those taking zinc for more than 2 months also need a copper supplement, as zinc reduces the amount of copper absorbed by the body.

Dr. Shi’s “do’s” diet list for acne patients is a follows: Paleolithic and Mediterranean diets, omega-3 fatty acids, gamma-linolenic acids, Vitamin D, zinc, tubers, legumes, vegetables, fruits, and fish.

Unknowns, she said, include chocolate, caffeine, green tea, and high salt.
 

Hidradenitis suppurativa

Patents with HS who follow a Mediterranean diet most closely have less severe disease, research has found. In this study, those patients with HS with the lowest adherence had a Sartorius HS score of 59.38, while those who followed it the most closely had a score of 39 (of 80).

In another study, patients with HS reported the following foods as exacerbating HS: sweets, bread/pasta/rice, dairy, and high-fat foods. Alleviating foods included vegetables, fruit, chicken, and fish.

Dr. Shi’s dietary recommendations for patients with HS: Follow a Mediterranean diet, avoid high fat foods and highly processed foods, and focus on eating more vegetables, fresh fruit, corn-based cereal, white meat, and fish.

A retrospective study of patients with Hurley stage 1 and 2 found that oral zinc gluconate, 90 mg a day, combined with 2% topical triclosan twice a day, resulted in significantly decreased HS scores and nodules and improved quality of life after 3 months. Expect vitamin D deficiency, she added.

Lastly, Dr. Shi recommended, if necessary, “weight loss to reduce the inflammatory burden.”
 

Rosacea

Dietary triggers for rosacea are thought to include high-fat foods, dairy foods, spicy foods, hot drinks, cinnamon, and vanilla.

A population-based case-control study in China, which evaluated 1,347 rosacea patients and 1,290 healthy controls, found that a high intake of fatty foods positively correlated with erythematotelangiectatic rosacea (ETR) and phymatous rosacea. High-frequency dairy intake negatively correlated with ETR and papulopustular rosacea, which was a surprise, she said. And in this study, no significant correlations were found between sweets, coffee, and spicy foods. That goes against the traditional thinking, she said, but this was a Chinese cohort and their diet is probably vastly different than those in the United States.

Other rosacea triggers, Dr. Shi said, are niacin-containing foods such as turkey, chicken breast, crustaceans, dried Shiitake mushrooms, peanuts, tuna, and liver, as well as cold drinks, and formalin-containing foods (fish, squid, tofu, wet noodles).

As the field of nutrigenics – how genes affect how the body responds to food – evolves, more answers about the impact of diet on these diseases will be forthcoming, Dr. Shi said.

In an interactive panel discussion, she was asked if she talks about diet with all her patients with acne, rosacea, and HS, or just those not responding to traditional therapy.

“I think it’s an important conversation to have,” Dr. Shi responded. “When I’m done with the medication [instructions], I say: ‘There is something else you can do to augment what I just told you.’ ” That’s when she explains the dietary information. She also has a handout on diet and routinely refers patients for dietary counseling.

MedscapeLive and this news organization are owned by the same parent company. Dr. Shi disclosed consulting, investigative and research funding from several sources, but not directly related to the content of her talk.

Since 1950, the terms “diet and skin” in the medical literature have markedly increased, said Vivian Shi, MD associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock, who talked about nutritional approaches for select skin diseases at MedscapeLive’s Women’s and Pediatric Dermatology Seminar.

Myths abound, but some associations of diet with skin diseases hold water, and diet tweaks could supplement treatments and improve results in patients with acne, hidradenitis suppurativa (HS), and rosacea, she said.
 

Acne

What’s known, Dr. Shi said, is that the prevalence of acne is substantially lower in non-Westernized countries, and that diets in those countries generally have a low glycemic load, which decreases IGF-1 insulinlike growth factor 1 (IGF-1) concentrations, an accepted risk factor for acne. The Western diet also includes the hormonal effects of cow’s milk products.

Whey protein, which is popular as a supplement, isn’t good for acne, Dr. Shi said. It takes a couple of hours to digest, while casein protein digests more slowly, over 5-7 hours. If casein protein isn’t acceptable, good alternatives to whey protein are hemp seed, plant protein blends (peas, seeds, berries), egg white, brown rice isolate, and soy isolate protein.

Dairy products increase IGF-1 levels, hormonal mediators that can make acne worse. In addition, industrial cow’s milk can contain anabolic steroids and growth factor, leading to sebogenesis, Dr. Shi said. As for the type of milk, skim milk tends to be the most acnegenic and associated with the highest blood levels of IGF-1.

Supplementing with omega-3 fatty acids and gamma-linolenic acid improved mild to moderate acne in a double-blind, controlled study. Researchers randomized 45 patients with mild to moderate acne to an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a gamma-linolenic acid group (borage oil with 400 mg gamma-linolenic acid) or a control group. After 10 weeks in both treatment groups, there was a significant reduction in inflammatory and noninflammatory lesions.

Those with acne are more likely to be deficient in Vitamin D, research suggests. Researchers also found that among those who had vitamin D deficiency, supplementing with 1,000 IU daily for 2 months reduced inflammatory lesions by 35% after 8 weeks, compared with a 6% reduction in the control group.

Other research has found that those with a low serum zinc level had more severe acne and that 30-200 mg of zinc orally for 2-4 months reduced inflammatory acne. However, Dr. Shi cautioned that those taking zinc for more than 2 months also need a copper supplement, as zinc reduces the amount of copper absorbed by the body.

Dr. Shi’s “do’s” diet list for acne patients is a follows: Paleolithic and Mediterranean diets, omega-3 fatty acids, gamma-linolenic acids, Vitamin D, zinc, tubers, legumes, vegetables, fruits, and fish.

Unknowns, she said, include chocolate, caffeine, green tea, and high salt.
 

Hidradenitis suppurativa

Patents with HS who follow a Mediterranean diet most closely have less severe disease, research has found. In this study, those patients with HS with the lowest adherence had a Sartorius HS score of 59.38, while those who followed it the most closely had a score of 39 (of 80).

In another study, patients with HS reported the following foods as exacerbating HS: sweets, bread/pasta/rice, dairy, and high-fat foods. Alleviating foods included vegetables, fruit, chicken, and fish.

Dr. Shi’s dietary recommendations for patients with HS: Follow a Mediterranean diet, avoid high fat foods and highly processed foods, and focus on eating more vegetables, fresh fruit, corn-based cereal, white meat, and fish.

A retrospective study of patients with Hurley stage 1 and 2 found that oral zinc gluconate, 90 mg a day, combined with 2% topical triclosan twice a day, resulted in significantly decreased HS scores and nodules and improved quality of life after 3 months. Expect vitamin D deficiency, she added.

Lastly, Dr. Shi recommended, if necessary, “weight loss to reduce the inflammatory burden.”
 

Rosacea

Dietary triggers for rosacea are thought to include high-fat foods, dairy foods, spicy foods, hot drinks, cinnamon, and vanilla.

A population-based case-control study in China, which evaluated 1,347 rosacea patients and 1,290 healthy controls, found that a high intake of fatty foods positively correlated with erythematotelangiectatic rosacea (ETR) and phymatous rosacea. High-frequency dairy intake negatively correlated with ETR and papulopustular rosacea, which was a surprise, she said. And in this study, no significant correlations were found between sweets, coffee, and spicy foods. That goes against the traditional thinking, she said, but this was a Chinese cohort and their diet is probably vastly different than those in the United States.

Other rosacea triggers, Dr. Shi said, are niacin-containing foods such as turkey, chicken breast, crustaceans, dried Shiitake mushrooms, peanuts, tuna, and liver, as well as cold drinks, and formalin-containing foods (fish, squid, tofu, wet noodles).

As the field of nutrigenics – how genes affect how the body responds to food – evolves, more answers about the impact of diet on these diseases will be forthcoming, Dr. Shi said.

In an interactive panel discussion, she was asked if she talks about diet with all her patients with acne, rosacea, and HS, or just those not responding to traditional therapy.

“I think it’s an important conversation to have,” Dr. Shi responded. “When I’m done with the medication [instructions], I say: ‘There is something else you can do to augment what I just told you.’ ” That’s when she explains the dietary information. She also has a handout on diet and routinely refers patients for dietary counseling.

MedscapeLive and this news organization are owned by the same parent company. Dr. Shi disclosed consulting, investigative and research funding from several sources, but not directly related to the content of her talk.

Alabama urged a federal court on June 28 to drop its block on the state’s ban on gender-affirming care for transgender youth, citing the Supreme Court’s recent decision to overturn Roe v. Wade.

Alabama Attorney General Steve Marshall said the high court ruled that abortion isn’t protected under the 14th Amendment because it’s not “deeply rooted” in the nation’s history, which he noted could be said about access to gender-affirming care as well, according to Axios.

“No one – adult or child – has a right to transitioning treatments that is deeply rooted in our Nation’s history and tradition,” he wrote in a court document.

“The State can thus regulate or prohibit those interventions for children, even if an adult wants the drugs for his child,” he wrote.

In May, a federal judge blocked part of Alabama’s Senate Bill 184, which makes it a felony for someone to “engage in or cause” certain types of medical care for transgender youths. The law, which was put in place in April, allows for criminal prosecution against doctors, parents, guardians, and anyone else who provides care to a minor. The penalties could result in up to 10 years in prison and up to $15,000 in fines.

At that time, U.S. District Judge Liles Burke issued an injunction to stop Alabama from enforcing the law and allow challenges, including one filed by the Department of Justice. Mr. Burke said the state provided “no credible evidence to show that transitioning medications are ‘experimental.’ ”

“While Defendants offer some evidence that transitioning medications pose certain risks, the uncontradicted record evidence is that at least twenty-two major medical associations in the United States endorse transitioning medications as well-established, evidence-based treatments for gender dysphoria in minors,” he wrote in the ruling.

Medical organizations such as the American Academy of Pediatrics, American Psychological Association, and American Medical Association have urged governors to oppose legislation this year that would restrict gender-affirming medical care, saying that such laws could have negative effects on the mental health of transgender youths.

But on June 28, Mr. Marshall focused on the Constitution and what he believes the recent overturn of Roe implies.

“Just as the parental relationship does not unlock a Due Process right allowing parents to obtain medical marijuana or abortions for their children, neither does it unlock a right to transitioning treatments,” he wrote.

“The Constitution reserves to the State – not courts or medical interest groups – the authority to determine that these sterilizing interventions are too dangerous for minors,” he said.

Since the Supreme Court overturned Roe, people have expressed concerns that lawsuits could now target several rights that are protected under the 14th Amendment, including same-sex relationships, marriage equality, and access to contraceptives.

Justice Clarence Thomas, who wrote a concurring opinion to the majority decision, said the Supreme Court, “in future cases” should reconsider “substantive due process precedents” under previous landmark cases such as Griswold v. Connecticut, Lawrence v. Texas, and Obergefell v. Hodges.

At the same time, Justice Brett Kavanaugh, who also wrote a concurring opinion, said the decision to overturn Roe was only focused on abortion, saying it “does not mean the overruling of those precedents, and does not threaten or cast doubt on those precedents.”

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

Alabama urged a federal court on June 28 to drop its block on the state’s ban on gender-affirming care for transgender youth, citing the Supreme Court’s recent decision to overturn Roe v. Wade.

Alabama Attorney General Steve Marshall said the high court ruled that abortion isn’t protected under the 14th Amendment because it’s not “deeply rooted” in the nation’s history, which he noted could be said about access to gender-affirming care as well, according to Axios.

“No one – adult or child – has a right to transitioning treatments that is deeply rooted in our Nation’s history and tradition,” he wrote in a court document.

“The State can thus regulate or prohibit those interventions for children, even if an adult wants the drugs for his child,” he wrote.

In May, a federal judge blocked part of Alabama’s Senate Bill 184, which makes it a felony for someone to “engage in or cause” certain types of medical care for transgender youths. The law, which was put in place in April, allows for criminal prosecution against doctors, parents, guardians, and anyone else who provides care to a minor. The penalties could result in up to 10 years in prison and up to $15,000 in fines.

At that time, U.S. District Judge Liles Burke issued an injunction to stop Alabama from enforcing the law and allow challenges, including one filed by the Department of Justice. Mr. Burke said the state provided “no credible evidence to show that transitioning medications are ‘experimental.’ ”

“While Defendants offer some evidence that transitioning medications pose certain risks, the uncontradicted record evidence is that at least twenty-two major medical associations in the United States endorse transitioning medications as well-established, evidence-based treatments for gender dysphoria in minors,” he wrote in the ruling.

Medical organizations such as the American Academy of Pediatrics, American Psychological Association, and American Medical Association have urged governors to oppose legislation this year that would restrict gender-affirming medical care, saying that such laws could have negative effects on the mental health of transgender youths.

But on June 28, Mr. Marshall focused on the Constitution and what he believes the recent overturn of Roe implies.

“Just as the parental relationship does not unlock a Due Process right allowing parents to obtain medical marijuana or abortions for their children, neither does it unlock a right to transitioning treatments,” he wrote.

“The Constitution reserves to the State – not courts or medical interest groups – the authority to determine that these sterilizing interventions are too dangerous for minors,” he said.

Since the Supreme Court overturned Roe, people have expressed concerns that lawsuits could now target several rights that are protected under the 14th Amendment, including same-sex relationships, marriage equality, and access to contraceptives.

Justice Clarence Thomas, who wrote a concurring opinion to the majority decision, said the Supreme Court, “in future cases” should reconsider “substantive due process precedents” under previous landmark cases such as Griswold v. Connecticut, Lawrence v. Texas, and Obergefell v. Hodges.

At the same time, Justice Brett Kavanaugh, who also wrote a concurring opinion, said the decision to overturn Roe was only focused on abortion, saying it “does not mean the overruling of those precedents, and does not threaten or cast doubt on those precedents.”

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

Alabama urged a federal court on June 28 to drop its block on the state’s ban on gender-affirming care for transgender youth, citing the Supreme Court’s recent decision to overturn Roe v. Wade.

Alabama Attorney General Steve Marshall said the high court ruled that abortion isn’t protected under the 14th Amendment because it’s not “deeply rooted” in the nation’s history, which he noted could be said about access to gender-affirming care as well, according to Axios.

“No one – adult or child – has a right to transitioning treatments that is deeply rooted in our Nation’s history and tradition,” he wrote in a court document.

“The State can thus regulate or prohibit those interventions for children, even if an adult wants the drugs for his child,” he wrote.

In May, a federal judge blocked part of Alabama’s Senate Bill 184, which makes it a felony for someone to “engage in or cause” certain types of medical care for transgender youths. The law, which was put in place in April, allows for criminal prosecution against doctors, parents, guardians, and anyone else who provides care to a minor. The penalties could result in up to 10 years in prison and up to $15,000 in fines.

At that time, U.S. District Judge Liles Burke issued an injunction to stop Alabama from enforcing the law and allow challenges, including one filed by the Department of Justice. Mr. Burke said the state provided “no credible evidence to show that transitioning medications are ‘experimental.’ ”

“While Defendants offer some evidence that transitioning medications pose certain risks, the uncontradicted record evidence is that at least twenty-two major medical associations in the United States endorse transitioning medications as well-established, evidence-based treatments for gender dysphoria in minors,” he wrote in the ruling.

Medical organizations such as the American Academy of Pediatrics, American Psychological Association, and American Medical Association have urged governors to oppose legislation this year that would restrict gender-affirming medical care, saying that such laws could have negative effects on the mental health of transgender youths.

But on June 28, Mr. Marshall focused on the Constitution and what he believes the recent overturn of Roe implies.

“Just as the parental relationship does not unlock a Due Process right allowing parents to obtain medical marijuana or abortions for their children, neither does it unlock a right to transitioning treatments,” he wrote.

“The Constitution reserves to the State – not courts or medical interest groups – the authority to determine that these sterilizing interventions are too dangerous for minors,” he said.

Since the Supreme Court overturned Roe, people have expressed concerns that lawsuits could now target several rights that are protected under the 14th Amendment, including same-sex relationships, marriage equality, and access to contraceptives.

Justice Clarence Thomas, who wrote a concurring opinion to the majority decision, said the Supreme Court, “in future cases” should reconsider “substantive due process precedents” under previous landmark cases such as Griswold v. Connecticut, Lawrence v. Texas, and Obergefell v. Hodges.

At the same time, Justice Brett Kavanaugh, who also wrote a concurring opinion, said the decision to overturn Roe was only focused on abortion, saying it “does not mean the overruling of those precedents, and does not threaten or cast doubt on those precedents.”

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

For generally healthy patients taking isotretinoin for acne and who have no underlying abnormalities or preexisting conditions that warrant further examination, it is sufficient to test ALT and triglycerides once at baseline, ideally within a month prior to the start of treatment, and a second time at peak dose.

Other tests such as complete blood cell counts and basic metabolic panels as well as specific laboratory tests such as LDL and HDL cholesterol should not be routinely monitored.

Those are key conclusions from a Delphi consensus study that included 22 acne experts from five continents and was published in JAMA Dermatology.

“Our results apply findings from recent literature and are in accordance with recent studies that have recommended against excessive laboratory monitoring,” senior corresponding author Arash Mostaghimi, MD, MPA, MPH, and coauthors wrote. “For instance, several studies in both teenagers and adults have shown that routine complete blood cell count laboratory tests are unnecessary without suspicion of an underlying abnormality and that rare abnormalities, if present, either resolved or remained stable without clinical impact on treatment. Likewise, liver function tests and lipid panels ordered at baseline and after 2 months of therapy were deemed sufficient if the clinical context and results do not suggest potential abnormalities.”

The authors also noted that, while published acne management guidelines exist, such as the American Academy of Dermatology work group guidelines and the National Institute for Health and Care Excellence guideline, “the specific recommendations surrounding laboratory monitoring frequency are nonstandardized and often nonspecific.”

To establish a consensus for isotretinoin laboratory monitoring, Dr. Mostaghimi, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to administer four rounds of electronic surveys to 22 board-certified dermatologists between 2021 and 2022. The primary outcome measured was whether participants could reach consensus on key isotretinoin lab monitoring parameters. Responses that failed to reach a threshold of 70% indicated no consensus.

The surveyed dermatologists had been in practice for a mean of 23.7 years, 54.5% were female, 54.5% practiced in an academic setting, and 63.9% were based in North America. They reached consensus for checking ALT within a month prior to initiation (89.5%) and at peak dose (89.5%), but not checking monthly (76.2%) or after completing treatment (73.7%). They also reached consensus on checking triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not to check monthly (84.2%) or after completing treatment (73.7%).

Meanwhile, consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all > 70%), as well as not checking gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), LDL cholesterol (73.7%), HDL cholesterol (73.7%), or C-reactive protein (77.3%).

“Additional research is required to determine best practices for laboratory measures that did not reach consensus,” the authors wrote. The study results “are intended to guide appropriate clinical decision-making,” they added. “Although our recommendations cannot replace clinical judgment based on the unique circumstances of individual patients, we believe they provide a framework for management of a typical, otherwise healthy patient being treated with isotretinoin for acne. More routine monitoring, or reduced monitoring, should be considered on a case-by-case basis accounting for the unique medical history, circumstances, and baseline abnormalities, if present, of each patient.”

“Practicing dermatologists, including myself, routinely check blood laboratory values during isotretinoin treatment,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “Even though just a small number of U.S.-based and international acne researchers were involved in this Delphi consensus statement, this article still makes us practicing clinicians feel more comfortable in checking fewer lab chemistries and also less frequently checking labs when we use isotretinoin.

“That said, I don’t think most of us are ready, because of legal reasons, to do that infrequent monitoring” during isotretinoin therapy, Dr. Green added. “I think most dermatologists do not routinely perform CBCs anymore, but we still feel obligated to check triglycerides and liver function more frequently” than recommended in the new study.

Dr. Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. Other authors reported serving as an adviser, a speaker consultant, investigator, and/or board member, or having received honoraria from different pharmaceutical companies; several authors had no disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

For generally healthy patients taking isotretinoin for acne and who have no underlying abnormalities or preexisting conditions that warrant further examination, it is sufficient to test ALT and triglycerides once at baseline, ideally within a month prior to the start of treatment, and a second time at peak dose.

Other tests such as complete blood cell counts and basic metabolic panels as well as specific laboratory tests such as LDL and HDL cholesterol should not be routinely monitored.

Those are key conclusions from a Delphi consensus study that included 22 acne experts from five continents and was published in JAMA Dermatology.

“Our results apply findings from recent literature and are in accordance with recent studies that have recommended against excessive laboratory monitoring,” senior corresponding author Arash Mostaghimi, MD, MPA, MPH, and coauthors wrote. “For instance, several studies in both teenagers and adults have shown that routine complete blood cell count laboratory tests are unnecessary without suspicion of an underlying abnormality and that rare abnormalities, if present, either resolved or remained stable without clinical impact on treatment. Likewise, liver function tests and lipid panels ordered at baseline and after 2 months of therapy were deemed sufficient if the clinical context and results do not suggest potential abnormalities.”

The authors also noted that, while published acne management guidelines exist, such as the American Academy of Dermatology work group guidelines and the National Institute for Health and Care Excellence guideline, “the specific recommendations surrounding laboratory monitoring frequency are nonstandardized and often nonspecific.”

To establish a consensus for isotretinoin laboratory monitoring, Dr. Mostaghimi, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to administer four rounds of electronic surveys to 22 board-certified dermatologists between 2021 and 2022. The primary outcome measured was whether participants could reach consensus on key isotretinoin lab monitoring parameters. Responses that failed to reach a threshold of 70% indicated no consensus.

The surveyed dermatologists had been in practice for a mean of 23.7 years, 54.5% were female, 54.5% practiced in an academic setting, and 63.9% were based in North America. They reached consensus for checking ALT within a month prior to initiation (89.5%) and at peak dose (89.5%), but not checking monthly (76.2%) or after completing treatment (73.7%). They also reached consensus on checking triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not to check monthly (84.2%) or after completing treatment (73.7%).

Meanwhile, consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all > 70%), as well as not checking gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), LDL cholesterol (73.7%), HDL cholesterol (73.7%), or C-reactive protein (77.3%).

“Additional research is required to determine best practices for laboratory measures that did not reach consensus,” the authors wrote. The study results “are intended to guide appropriate clinical decision-making,” they added. “Although our recommendations cannot replace clinical judgment based on the unique circumstances of individual patients, we believe they provide a framework for management of a typical, otherwise healthy patient being treated with isotretinoin for acne. More routine monitoring, or reduced monitoring, should be considered on a case-by-case basis accounting for the unique medical history, circumstances, and baseline abnormalities, if present, of each patient.”

“Practicing dermatologists, including myself, routinely check blood laboratory values during isotretinoin treatment,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “Even though just a small number of U.S.-based and international acne researchers were involved in this Delphi consensus statement, this article still makes us practicing clinicians feel more comfortable in checking fewer lab chemistries and also less frequently checking labs when we use isotretinoin.

“That said, I don’t think most of us are ready, because of legal reasons, to do that infrequent monitoring” during isotretinoin therapy, Dr. Green added. “I think most dermatologists do not routinely perform CBCs anymore, but we still feel obligated to check triglycerides and liver function more frequently” than recommended in the new study.

Dr. Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. Other authors reported serving as an adviser, a speaker consultant, investigator, and/or board member, or having received honoraria from different pharmaceutical companies; several authors had no disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

For generally healthy patients taking isotretinoin for acne and who have no underlying abnormalities or preexisting conditions that warrant further examination, it is sufficient to test ALT and triglycerides once at baseline, ideally within a month prior to the start of treatment, and a second time at peak dose.

Other tests such as complete blood cell counts and basic metabolic panels as well as specific laboratory tests such as LDL and HDL cholesterol should not be routinely monitored.

Those are key conclusions from a Delphi consensus study that included 22 acne experts from five continents and was published in JAMA Dermatology.

“Our results apply findings from recent literature and are in accordance with recent studies that have recommended against excessive laboratory monitoring,” senior corresponding author Arash Mostaghimi, MD, MPA, MPH, and coauthors wrote. “For instance, several studies in both teenagers and adults have shown that routine complete blood cell count laboratory tests are unnecessary without suspicion of an underlying abnormality and that rare abnormalities, if present, either resolved or remained stable without clinical impact on treatment. Likewise, liver function tests and lipid panels ordered at baseline and after 2 months of therapy were deemed sufficient if the clinical context and results do not suggest potential abnormalities.”

The authors also noted that, while published acne management guidelines exist, such as the American Academy of Dermatology work group guidelines and the National Institute for Health and Care Excellence guideline, “the specific recommendations surrounding laboratory monitoring frequency are nonstandardized and often nonspecific.”

To establish a consensus for isotretinoin laboratory monitoring, Dr. Mostaghimi, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to administer four rounds of electronic surveys to 22 board-certified dermatologists between 2021 and 2022. The primary outcome measured was whether participants could reach consensus on key isotretinoin lab monitoring parameters. Responses that failed to reach a threshold of 70% indicated no consensus.

The surveyed dermatologists had been in practice for a mean of 23.7 years, 54.5% were female, 54.5% practiced in an academic setting, and 63.9% were based in North America. They reached consensus for checking ALT within a month prior to initiation (89.5%) and at peak dose (89.5%), but not checking monthly (76.2%) or after completing treatment (73.7%). They also reached consensus on checking triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not to check monthly (84.2%) or after completing treatment (73.7%).

Meanwhile, consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all > 70%), as well as not checking gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), LDL cholesterol (73.7%), HDL cholesterol (73.7%), or C-reactive protein (77.3%).

“Additional research is required to determine best practices for laboratory measures that did not reach consensus,” the authors wrote. The study results “are intended to guide appropriate clinical decision-making,” they added. “Although our recommendations cannot replace clinical judgment based on the unique circumstances of individual patients, we believe they provide a framework for management of a typical, otherwise healthy patient being treated with isotretinoin for acne. More routine monitoring, or reduced monitoring, should be considered on a case-by-case basis accounting for the unique medical history, circumstances, and baseline abnormalities, if present, of each patient.”

“Practicing dermatologists, including myself, routinely check blood laboratory values during isotretinoin treatment,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “Even though just a small number of U.S.-based and international acne researchers were involved in this Delphi consensus statement, this article still makes us practicing clinicians feel more comfortable in checking fewer lab chemistries and also less frequently checking labs when we use isotretinoin.

“That said, I don’t think most of us are ready, because of legal reasons, to do that infrequent monitoring” during isotretinoin therapy, Dr. Green added. “I think most dermatologists do not routinely perform CBCs anymore, but we still feel obligated to check triglycerides and liver function more frequently” than recommended in the new study.

Dr. Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. Other authors reported serving as an adviser, a speaker consultant, investigator, and/or board member, or having received honoraria from different pharmaceutical companies; several authors had no disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

According to the US Department of Defense, the term readiness refers to the ability to recruit, train, deploy, and sustain military forces that will be ready to “fight tonight” and succeed in combat. Readiness is a top priority for military medicine, which functions to diagnose, treat, and rehabilitate service members so that they can return to the fight. This central concept drives programs across the military—from operational training events to the establishment of medical and dental standards. Readiness is tracked and scrutinized constantly, and although it is a shared responsibility, efforts to increase and sustain readiness often fall on support staff and military medical providers.

In recent years, there has been a greater awareness of the negative effects of mental illness, low morale, and suicidality on military readiness. In 2013, suicide accounted for 28.1% of all deaths that occurred in the US Armed Forces.¹ Put frankly, suicide was one of the leading causes of death among military members.

The most recent Marine Corps Order regarding the Marine Corps Suicide Prevention Program stated that “suicidal behaviors are a barrier to readiness that have lasting effects on Marines and Service Members attached to Marine Commands. . .Families, and the Marine Corps.” It goes on to say that “[e]ffective suicide prevention requires coordinated efforts within a prevention framework dedicated to promoting mental, physical, spiritual, and social fitness. . .[and] mitigating stressors that interfere with mission readiness.”² This statement supports the notion that preventing suicide is not just about treating mental illness; it also involves maximizing physical, spiritual, and social fitness. Although it is well established that various mental health disorders are associated with an increased risk for suicide, it is worth noting that, in one study, only half of individuals who died by suicide had a mental health disorder diagnosed prior to their death.³ These statistics translate to the military. The 2015 Department of Defense Suicide Event Report noted that only 28% of service members who died by suicide and 22% of members with attempted suicide had been documented as having sought mental health care and disclosed their potential for self-harm prior to the event.^1,4 In 2018, a study published by Ursano et al⁵ showed that 36.3% of US soldiers with a documented suicide attempt (N=9650) had no prior mental health diagnoses.

Expanding the scope to include mental health issues in general, only 29% of service members who reported experiencing a mental health problem actually sought mental health care in that same period. Overall, approximately 40% of service members with a reported perceived need for mental health care actually sought care over their entire course of service time,¹ which raises concern for a large population of undiagnosed and undertreated mental illnesses across the military. In response to these statistics, Reger et al³ posited that it is “essential that suicide prevention efforts move outside the silo of mental health.” The authors went on to challenge health care providers across all specialties and civilians alike to take responsibility in understanding, recognizing, and mitigating risk factors for suicide in the general population.³ Although treating a service member’s acne or offering to stand duty for a service member who has been under a great deal of stress in their personal life may appear to be indirect ways of reducing suicide in the US military, they actually may be the most critical means of prevention in a culture that emphasizes resilience and self-reliance, where seeking help for mental health struggles could be perceived as weakness.¹

In this review article, we discuss the concept of cutaneous body image (CBI) and its associated outcomes on health, satisfaction, and quality of life in military service members. We then examine the intersections between common dermatologic conditions, CBI, and mental health and explore the ability and role of the military dermatologist to serve as a positive influence on military readiness.

What is cutaneous body image?

Cutaneous body image is “the individual’s mental perception of his or her skin and its appendages (ie, hair, nails).”⁶ It is measured objectively using the Cutaneous Body Image Scale, a questionnaire that includes 7 items related to the overall satisfaction with the appearance of skin, color of skin, skin of the face, complexion of the face, hair, fingernails, and toenails. Each question is rated using a 10-point Likert scale (0=not at all; 10=very markedly).⁶

Some degree of CBI dissatisfaction is expected and has been shown in the general population at large; for example, more than 56% of women older than 30 years report some degree of dissatisfaction with their skin. Similarly, data from the American Society of Plastic Surgeons showed that while 10.9 million cosmetic procedures were performed in 2006, 9.1 million of them involved minimally invasive procedures such as botulinum toxin type A injections with the purpose of skin rejuvenation and improvement of facial appearance.⁷ However, lower than average CBI can contribute to considerable psychosocial morbidity. Dissatisfaction with CBI is associated with self-consciousness, feelings of inferiority, and social exclusion. These symptoms can be grouped into a construct called interpersonal sensitivity (IS). A 2013 study by Gupta and Gupta⁶ investigated the relationship between CBI, IS, and suicidal ideation among 312 consenting nonclinical participants in Canada. The study found that greater dissatisfaction with an individual’s CBI correlated to increased IS and increased rates of suicidal ideation and intentional self-injury.⁶

Cutaneous body image is particularly relevant to dermatologists, as many common dermatoses can cause cosmetically disfiguring skin conditions; for example, acne and rosacea have the propensity to cause notable disfigurement to the facial unit. Other common conditions such as atopic dermatitis or psoriasis can flare with stress and thereby throw patients into a vicious cycle of physical and psychosocial stress caused by social stigma, cosmetic disfigurement, and reduced CBI, in turn leading to worsening of the disease at hand. Dermatologists need to be aware that common dermatoses can impact a patient’s mental health via poor CBI.⁸ Similarly, dermatologists may be empowered by the awareness that treating common dermatoses, especially those associated with poor cosmesis, have 2-fold benefits—on the skin condition itself and on the patient’s mental health.

How are common dermatoses associated with mental health?

Acne—Acne is one of the most common skin diseases, so much so that in many cases acne has become an accepted and expected part of adolescence and young adulthood. Studies estimate that 85% of the US population aged 12 to 25 years have acne.⁹ For some adults, acne persists even longer, with 1% to 5% of adults reporting to have active lesions at 40 years of age.¹⁰ Acne is a multifactorial skin disease of the pilosebaceous unit that results in the development of inflammatory papules, pustules, and cysts. These lesions are most common on the face but can extend to other areas of the body, such as the chest and back.¹¹ Although the active lesions can be painful and disfiguring, if left untreated, acne may lead to permanent disfigurement and scarring, which can have long-lasting psychosocial impacts.

Individuals with acne have an increased likelihood of self-consciousness, social isolation, depression, and suicidal ideation. This relationship has been well established for decades. In the 1990s, a small study reported that 7 of 16 (43.8%) cases of completed suicide in dermatology patients were in patients with acne.¹² In a recent meta-analysis including 2,276,798 participants across 5 separate studies, researchers found that suicide was positively associated with acne, carrying an odds ratio of 1.50 (95% CI, 1.09-2.06).¹³

Rosacea—Rosacea is a common chronic inflammatory skin disease characterized by facial erythema, telangiectasia, phymatous changes, papules, pustules, and ocular irritation. The estimated worldwide prevalence is 5.5%.¹⁴ In addition to discomfort and irritation of the skin and eyes, rosacea often carries a higher risk of psychological and psychosocial distress due to its potentially disfiguring nature. Rosacea patients are at greater risk for having anxiety disorders and depression,¹⁵ and a 2018 study by Alinia et al¹⁶ showed that there is a direct relationship between rosacea severity and the actual level of depression.Although disease improvement certainly leads to improvements in quality of life and psychosocial status, Alinia et al¹⁶ noted that depression often is associated with poor treatment adherence due to poor motivation and hopelessness. It is critical that dermatologists are aware of these associations and maintain close follow-up with patients, even when the condition is not life-threatening, such as rosacea.

Hidradenitis Suppurativa—Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the pilosebaceous unit that is characterized by the development of painful, malodorous, draining abscesses, fistulas, sinus tracts, and scars in sensitive areas such as the axillae, breasts, groin, and perineum.¹⁷ In severe cases, surgery may be required to excise affected areas. Compared to other cutaneous disease, HS is considered one of the most life-impacting disorders.¹⁸ The physical symptoms themselves often are debilitating, and patients often report considerable psychosocial and psychological impairment with decreased quality of life. Major depression frequently is noted, with 1 in 4 adults with HS also being depressed. In a large cross-sectional analysis of 38,140 adults and 1162 pediatric patients with HS, Wright et al¹⁷ reported the prevalence of depression among adults with HS as 30.0% compared to 16.9% in healthy controls. In children, the prevalence of depression was 11.7% compared to 4.1% in the general population.¹⁷ Similarly, 1 out of every 5 patients with HS experiences anxiety.¹⁸

In the military population, HS often can be duty limiting. The disease requires constant attention to wound care and frequent medical visits. For many service members operating in field training or combat environments, opportunities for and access to showers and basic hygiene is limited. Uniforms and additional necessary combat gear often are thick and occlusive. Taken as a whole, these factors may contribute to worsening of the disease and in severe cases are simply not conducive to the successful management of the condition. However, given the most commonly involved body areas and the nature of the disease, many service members with HS may feel embarrassed to disclose their condition. In uniform, the disease is not easily visible, and for unaware persons, the frequency of medical visits and limited duty status may seem unnecessary. This perception of a service member’s lack of productivity due to an unseen disease may further add to the psychosocial stress they experience.

What treatment options can be considered for military service members?

The treatments for acne, rosacea, and HS are outlined in the eTable.^11,19 Also noted are specific considerations when managing an active-duty service member due to various operational duty restrictions and constraints.

Final Thoughts

Maintaining readiness in the military is essential to the ability to not only “fight tonight” but also to win tonight in whatever operational or combat mission a service member may be. Although many factors impact readiness, the rates of suicide within the armed forces cannot be ignored. Suicide not only eliminates the readiness of the deceased service member but has lasting ripple effects on the overall readiness of their unit and command at large. Most suicides in the military occur in personnel with no prior documented mental health diagnoses or treatment. Therefore, it is the responsibility of all service members to recognize and mitigate stressors and risk factors that may lead to mental health distress and suicidality. In the medical corps, this translates to a responsibility of all medical specialists to recognize and understand unique risk factors for suicidality and to do as much as they can to reduce these risks. For military dermatologists and for civilian physicians treating military service members, it is imperative to predict and understand the relationship between common dermatoses; reduced satisfaction with CBI; and increased risk for mental health illness, self-harm, and suicide. Military dermatologists, as well as other specialists, may be limited in the care they are able to provide due to manpower, staffing, demand, and institutional guidelines; however, to better serve those who serve in a holistic manner, consideration must be given to rethink what is “medically essential” and “cosmetic” and leverage the available skills, techniques, and equipment to increase the readiness of the force.

According to the US Department of Defense, the term readiness refers to the ability to recruit, train, deploy, and sustain military forces that will be ready to “fight tonight” and succeed in combat. Readiness is a top priority for military medicine, which functions to diagnose, treat, and rehabilitate service members so that they can return to the fight. This central concept drives programs across the military—from operational training events to the establishment of medical and dental standards. Readiness is tracked and scrutinized constantly, and although it is a shared responsibility, efforts to increase and sustain readiness often fall on support staff and military medical providers.

In recent years, there has been a greater awareness of the negative effects of mental illness, low morale, and suicidality on military readiness. In 2013, suicide accounted for 28.1% of all deaths that occurred in the US Armed Forces.¹ Put frankly, suicide was one of the leading causes of death among military members.

The most recent Marine Corps Order regarding the Marine Corps Suicide Prevention Program stated that “suicidal behaviors are a barrier to readiness that have lasting effects on Marines and Service Members attached to Marine Commands. . .Families, and the Marine Corps.” It goes on to say that “[e]ffective suicide prevention requires coordinated efforts within a prevention framework dedicated to promoting mental, physical, spiritual, and social fitness. . .[and] mitigating stressors that interfere with mission readiness.”² This statement supports the notion that preventing suicide is not just about treating mental illness; it also involves maximizing physical, spiritual, and social fitness. Although it is well established that various mental health disorders are associated with an increased risk for suicide, it is worth noting that, in one study, only half of individuals who died by suicide had a mental health disorder diagnosed prior to their death.³ These statistics translate to the military. The 2015 Department of Defense Suicide Event Report noted that only 28% of service members who died by suicide and 22% of members with attempted suicide had been documented as having sought mental health care and disclosed their potential for self-harm prior to the event.^1,4 In 2018, a study published by Ursano et al⁵ showed that 36.3% of US soldiers with a documented suicide attempt (N=9650) had no prior mental health diagnoses.

Expanding the scope to include mental health issues in general, only 29% of service members who reported experiencing a mental health problem actually sought mental health care in that same period. Overall, approximately 40% of service members with a reported perceived need for mental health care actually sought care over their entire course of service time,¹ which raises concern for a large population of undiagnosed and undertreated mental illnesses across the military. In response to these statistics, Reger et al³ posited that it is “essential that suicide prevention efforts move outside the silo of mental health.” The authors went on to challenge health care providers across all specialties and civilians alike to take responsibility in understanding, recognizing, and mitigating risk factors for suicide in the general population.³ Although treating a service member’s acne or offering to stand duty for a service member who has been under a great deal of stress in their personal life may appear to be indirect ways of reducing suicide in the US military, they actually may be the most critical means of prevention in a culture that emphasizes resilience and self-reliance, where seeking help for mental health struggles could be perceived as weakness.¹

In this review article, we discuss the concept of cutaneous body image (CBI) and its associated outcomes on health, satisfaction, and quality of life in military service members. We then examine the intersections between common dermatologic conditions, CBI, and mental health and explore the ability and role of the military dermatologist to serve as a positive influence on military readiness.

What is cutaneous body image?

Cutaneous body image is “the individual’s mental perception of his or her skin and its appendages (ie, hair, nails).”⁶ It is measured objectively using the Cutaneous Body Image Scale, a questionnaire that includes 7 items related to the overall satisfaction with the appearance of skin, color of skin, skin of the face, complexion of the face, hair, fingernails, and toenails. Each question is rated using a 10-point Likert scale (0=not at all; 10=very markedly).⁶

Some degree of CBI dissatisfaction is expected and has been shown in the general population at large; for example, more than 56% of women older than 30 years report some degree of dissatisfaction with their skin. Similarly, data from the American Society of Plastic Surgeons showed that while 10.9 million cosmetic procedures were performed in 2006, 9.1 million of them involved minimally invasive procedures such as botulinum toxin type A injections with the purpose of skin rejuvenation and improvement of facial appearance.⁷ However, lower than average CBI can contribute to considerable psychosocial morbidity. Dissatisfaction with CBI is associated with self-consciousness, feelings of inferiority, and social exclusion. These symptoms can be grouped into a construct called interpersonal sensitivity (IS). A 2013 study by Gupta and Gupta⁶ investigated the relationship between CBI, IS, and suicidal ideation among 312 consenting nonclinical participants in Canada. The study found that greater dissatisfaction with an individual’s CBI correlated to increased IS and increased rates of suicidal ideation and intentional self-injury.⁶

Cutaneous body image is particularly relevant to dermatologists, as many common dermatoses can cause cosmetically disfiguring skin conditions; for example, acne and rosacea have the propensity to cause notable disfigurement to the facial unit. Other common conditions such as atopic dermatitis or psoriasis can flare with stress and thereby throw patients into a vicious cycle of physical and psychosocial stress caused by social stigma, cosmetic disfigurement, and reduced CBI, in turn leading to worsening of the disease at hand. Dermatologists need to be aware that common dermatoses can impact a patient’s mental health via poor CBI.⁸ Similarly, dermatologists may be empowered by the awareness that treating common dermatoses, especially those associated with poor cosmesis, have 2-fold benefits—on the skin condition itself and on the patient’s mental health.

How are common dermatoses associated with mental health?

Acne—Acne is one of the most common skin diseases, so much so that in many cases acne has become an accepted and expected part of adolescence and young adulthood. Studies estimate that 85% of the US population aged 12 to 25 years have acne.⁹ For some adults, acne persists even longer, with 1% to 5% of adults reporting to have active lesions at 40 years of age.¹⁰ Acne is a multifactorial skin disease of the pilosebaceous unit that results in the development of inflammatory papules, pustules, and cysts. These lesions are most common on the face but can extend to other areas of the body, such as the chest and back.¹¹ Although the active lesions can be painful and disfiguring, if left untreated, acne may lead to permanent disfigurement and scarring, which can have long-lasting psychosocial impacts.

Individuals with acne have an increased likelihood of self-consciousness, social isolation, depression, and suicidal ideation. This relationship has been well established for decades. In the 1990s, a small study reported that 7 of 16 (43.8%) cases of completed suicide in dermatology patients were in patients with acne.¹² In a recent meta-analysis including 2,276,798 participants across 5 separate studies, researchers found that suicide was positively associated with acne, carrying an odds ratio of 1.50 (95% CI, 1.09-2.06).¹³

Rosacea—Rosacea is a common chronic inflammatory skin disease characterized by facial erythema, telangiectasia, phymatous changes, papules, pustules, and ocular irritation. The estimated worldwide prevalence is 5.5%.¹⁴ In addition to discomfort and irritation of the skin and eyes, rosacea often carries a higher risk of psychological and psychosocial distress due to its potentially disfiguring nature. Rosacea patients are at greater risk for having anxiety disorders and depression,¹⁵ and a 2018 study by Alinia et al¹⁶ showed that there is a direct relationship between rosacea severity and the actual level of depression.Although disease improvement certainly leads to improvements in quality of life and psychosocial status, Alinia et al¹⁶ noted that depression often is associated with poor treatment adherence due to poor motivation and hopelessness. It is critical that dermatologists are aware of these associations and maintain close follow-up with patients, even when the condition is not life-threatening, such as rosacea.

Hidradenitis Suppurativa—Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the pilosebaceous unit that is characterized by the development of painful, malodorous, draining abscesses, fistulas, sinus tracts, and scars in sensitive areas such as the axillae, breasts, groin, and perineum.¹⁷ In severe cases, surgery may be required to excise affected areas. Compared to other cutaneous disease, HS is considered one of the most life-impacting disorders.¹⁸ The physical symptoms themselves often are debilitating, and patients often report considerable psychosocial and psychological impairment with decreased quality of life. Major depression frequently is noted, with 1 in 4 adults with HS also being depressed. In a large cross-sectional analysis of 38,140 adults and 1162 pediatric patients with HS, Wright et al¹⁷ reported the prevalence of depression among adults with HS as 30.0% compared to 16.9% in healthy controls. In children, the prevalence of depression was 11.7% compared to 4.1% in the general population.¹⁷ Similarly, 1 out of every 5 patients with HS experiences anxiety.¹⁸

In the military population, HS often can be duty limiting. The disease requires constant attention to wound care and frequent medical visits. For many service members operating in field training or combat environments, opportunities for and access to showers and basic hygiene is limited. Uniforms and additional necessary combat gear often are thick and occlusive. Taken as a whole, these factors may contribute to worsening of the disease and in severe cases are simply not conducive to the successful management of the condition. However, given the most commonly involved body areas and the nature of the disease, many service members with HS may feel embarrassed to disclose their condition. In uniform, the disease is not easily visible, and for unaware persons, the frequency of medical visits and limited duty status may seem unnecessary. This perception of a service member’s lack of productivity due to an unseen disease may further add to the psychosocial stress they experience.

What treatment options can be considered for military service members?

The treatments for acne, rosacea, and HS are outlined in the eTable.^11,19 Also noted are specific considerations when managing an active-duty service member due to various operational duty restrictions and constraints.

Final Thoughts

Maintaining readiness in the military is essential to the ability to not only “fight tonight” but also to win tonight in whatever operational or combat mission a service member may be. Although many factors impact readiness, the rates of suicide within the armed forces cannot be ignored. Suicide not only eliminates the readiness of the deceased service member but has lasting ripple effects on the overall readiness of their unit and command at large. Most suicides in the military occur in personnel with no prior documented mental health diagnoses or treatment. Therefore, it is the responsibility of all service members to recognize and mitigate stressors and risk factors that may lead to mental health distress and suicidality. In the medical corps, this translates to a responsibility of all medical specialists to recognize and understand unique risk factors for suicidality and to do as much as they can to reduce these risks. For military dermatologists and for civilian physicians treating military service members, it is imperative to predict and understand the relationship between common dermatoses; reduced satisfaction with CBI; and increased risk for mental health illness, self-harm, and suicide. Military dermatologists, as well as other specialists, may be limited in the care they are able to provide due to manpower, staffing, demand, and institutional guidelines; however, to better serve those who serve in a holistic manner, consideration must be given to rethink what is “medically essential” and “cosmetic” and leverage the available skills, techniques, and equipment to increase the readiness of the force.

According to the US Department of Defense, the term readiness refers to the ability to recruit, train, deploy, and sustain military forces that will be ready to “fight tonight” and succeed in combat. Readiness is a top priority for military medicine, which functions to diagnose, treat, and rehabilitate service members so that they can return to the fight. This central concept drives programs across the military—from operational training events to the establishment of medical and dental standards. Readiness is tracked and scrutinized constantly, and although it is a shared responsibility, efforts to increase and sustain readiness often fall on support staff and military medical providers.

In recent years, there has been a greater awareness of the negative effects of mental illness, low morale, and suicidality on military readiness. In 2013, suicide accounted for 28.1% of all deaths that occurred in the US Armed Forces.¹ Put frankly, suicide was one of the leading causes of death among military members.

The most recent Marine Corps Order regarding the Marine Corps Suicide Prevention Program stated that “suicidal behaviors are a barrier to readiness that have lasting effects on Marines and Service Members attached to Marine Commands. . .Families, and the Marine Corps.” It goes on to say that “[e]ffective suicide prevention requires coordinated efforts within a prevention framework dedicated to promoting mental, physical, spiritual, and social fitness. . .[and] mitigating stressors that interfere with mission readiness.”² This statement supports the notion that preventing suicide is not just about treating mental illness; it also involves maximizing physical, spiritual, and social fitness. Although it is well established that various mental health disorders are associated with an increased risk for suicide, it is worth noting that, in one study, only half of individuals who died by suicide had a mental health disorder diagnosed prior to their death.³ These statistics translate to the military. The 2015 Department of Defense Suicide Event Report noted that only 28% of service members who died by suicide and 22% of members with attempted suicide had been documented as having sought mental health care and disclosed their potential for self-harm prior to the event.^1,4 In 2018, a study published by Ursano et al⁵ showed that 36.3% of US soldiers with a documented suicide attempt (N=9650) had no prior mental health diagnoses.

Expanding the scope to include mental health issues in general, only 29% of service members who reported experiencing a mental health problem actually sought mental health care in that same period. Overall, approximately 40% of service members with a reported perceived need for mental health care actually sought care over their entire course of service time,¹ which raises concern for a large population of undiagnosed and undertreated mental illnesses across the military. In response to these statistics, Reger et al³ posited that it is “essential that suicide prevention efforts move outside the silo of mental health.” The authors went on to challenge health care providers across all specialties and civilians alike to take responsibility in understanding, recognizing, and mitigating risk factors for suicide in the general population.³ Although treating a service member’s acne or offering to stand duty for a service member who has been under a great deal of stress in their personal life may appear to be indirect ways of reducing suicide in the US military, they actually may be the most critical means of prevention in a culture that emphasizes resilience and self-reliance, where seeking help for mental health struggles could be perceived as weakness.¹

In this review article, we discuss the concept of cutaneous body image (CBI) and its associated outcomes on health, satisfaction, and quality of life in military service members. We then examine the intersections between common dermatologic conditions, CBI, and mental health and explore the ability and role of the military dermatologist to serve as a positive influence on military readiness.

What is cutaneous body image?

Cutaneous body image is “the individual’s mental perception of his or her skin and its appendages (ie, hair, nails).”⁶ It is measured objectively using the Cutaneous Body Image Scale, a questionnaire that includes 7 items related to the overall satisfaction with the appearance of skin, color of skin, skin of the face, complexion of the face, hair, fingernails, and toenails. Each question is rated using a 10-point Likert scale (0=not at all; 10=very markedly).⁶

Some degree of CBI dissatisfaction is expected and has been shown in the general population at large; for example, more than 56% of women older than 30 years report some degree of dissatisfaction with their skin. Similarly, data from the American Society of Plastic Surgeons showed that while 10.9 million cosmetic procedures were performed in 2006, 9.1 million of them involved minimally invasive procedures such as botulinum toxin type A injections with the purpose of skin rejuvenation and improvement of facial appearance.⁷ However, lower than average CBI can contribute to considerable psychosocial morbidity. Dissatisfaction with CBI is associated with self-consciousness, feelings of inferiority, and social exclusion. These symptoms can be grouped into a construct called interpersonal sensitivity (IS). A 2013 study by Gupta and Gupta⁶ investigated the relationship between CBI, IS, and suicidal ideation among 312 consenting nonclinical participants in Canada. The study found that greater dissatisfaction with an individual’s CBI correlated to increased IS and increased rates of suicidal ideation and intentional self-injury.⁶

Cutaneous body image is particularly relevant to dermatologists, as many common dermatoses can cause cosmetically disfiguring skin conditions; for example, acne and rosacea have the propensity to cause notable disfigurement to the facial unit. Other common conditions such as atopic dermatitis or psoriasis can flare with stress and thereby throw patients into a vicious cycle of physical and psychosocial stress caused by social stigma, cosmetic disfigurement, and reduced CBI, in turn leading to worsening of the disease at hand. Dermatologists need to be aware that common dermatoses can impact a patient’s mental health via poor CBI.⁸ Similarly, dermatologists may be empowered by the awareness that treating common dermatoses, especially those associated with poor cosmesis, have 2-fold benefits—on the skin condition itself and on the patient’s mental health.

How are common dermatoses associated with mental health?

Acne—Acne is one of the most common skin diseases, so much so that in many cases acne has become an accepted and expected part of adolescence and young adulthood. Studies estimate that 85% of the US population aged 12 to 25 years have acne.⁹ For some adults, acne persists even longer, with 1% to 5% of adults reporting to have active lesions at 40 years of age.¹⁰ Acne is a multifactorial skin disease of the pilosebaceous unit that results in the development of inflammatory papules, pustules, and cysts. These lesions are most common on the face but can extend to other areas of the body, such as the chest and back.¹¹ Although the active lesions can be painful and disfiguring, if left untreated, acne may lead to permanent disfigurement and scarring, which can have long-lasting psychosocial impacts.

Individuals with acne have an increased likelihood of self-consciousness, social isolation, depression, and suicidal ideation. This relationship has been well established for decades. In the 1990s, a small study reported that 7 of 16 (43.8%) cases of completed suicide in dermatology patients were in patients with acne.¹² In a recent meta-analysis including 2,276,798 participants across 5 separate studies, researchers found that suicide was positively associated with acne, carrying an odds ratio of 1.50 (95% CI, 1.09-2.06).¹³

Rosacea—Rosacea is a common chronic inflammatory skin disease characterized by facial erythema, telangiectasia, phymatous changes, papules, pustules, and ocular irritation. The estimated worldwide prevalence is 5.5%.¹⁴ In addition to discomfort and irritation of the skin and eyes, rosacea often carries a higher risk of psychological and psychosocial distress due to its potentially disfiguring nature. Rosacea patients are at greater risk for having anxiety disorders and depression,¹⁵ and a 2018 study by Alinia et al¹⁶ showed that there is a direct relationship between rosacea severity and the actual level of depression.Although disease improvement certainly leads to improvements in quality of life and psychosocial status, Alinia et al¹⁶ noted that depression often is associated with poor treatment adherence due to poor motivation and hopelessness. It is critical that dermatologists are aware of these associations and maintain close follow-up with patients, even when the condition is not life-threatening, such as rosacea.

Hidradenitis Suppurativa—Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the pilosebaceous unit that is characterized by the development of painful, malodorous, draining abscesses, fistulas, sinus tracts, and scars in sensitive areas such as the axillae, breasts, groin, and perineum.¹⁷ In severe cases, surgery may be required to excise affected areas. Compared to other cutaneous disease, HS is considered one of the most life-impacting disorders.¹⁸ The physical symptoms themselves often are debilitating, and patients often report considerable psychosocial and psychological impairment with decreased quality of life. Major depression frequently is noted, with 1 in 4 adults with HS also being depressed. In a large cross-sectional analysis of 38,140 adults and 1162 pediatric patients with HS, Wright et al¹⁷ reported the prevalence of depression among adults with HS as 30.0% compared to 16.9% in healthy controls. In children, the prevalence of depression was 11.7% compared to 4.1% in the general population.¹⁷ Similarly, 1 out of every 5 patients with HS experiences anxiety.¹⁸

In the military population, HS often can be duty limiting. The disease requires constant attention to wound care and frequent medical visits. For many service members operating in field training or combat environments, opportunities for and access to showers and basic hygiene is limited. Uniforms and additional necessary combat gear often are thick and occlusive. Taken as a whole, these factors may contribute to worsening of the disease and in severe cases are simply not conducive to the successful management of the condition. However, given the most commonly involved body areas and the nature of the disease, many service members with HS may feel embarrassed to disclose their condition. In uniform, the disease is not easily visible, and for unaware persons, the frequency of medical visits and limited duty status may seem unnecessary. This perception of a service member’s lack of productivity due to an unseen disease may further add to the psychosocial stress they experience.

What treatment options can be considered for military service members?

The treatments for acne, rosacea, and HS are outlined in the eTable.^11,19 Also noted are specific considerations when managing an active-duty service member due to various operational duty restrictions and constraints.

Final Thoughts

Maintaining readiness in the military is essential to the ability to not only “fight tonight” but also to win tonight in whatever operational or combat mission a service member may be. Although many factors impact readiness, the rates of suicide within the armed forces cannot be ignored. Suicide not only eliminates the readiness of the deceased service member but has lasting ripple effects on the overall readiness of their unit and command at large. Most suicides in the military occur in personnel with no prior documented mental health diagnoses or treatment. Therefore, it is the responsibility of all service members to recognize and mitigate stressors and risk factors that may lead to mental health distress and suicidality. In the medical corps, this translates to a responsibility of all medical specialists to recognize and understand unique risk factors for suicidality and to do as much as they can to reduce these risks. For military dermatologists and for civilian physicians treating military service members, it is imperative to predict and understand the relationship between common dermatoses; reduced satisfaction with CBI; and increased risk for mental health illness, self-harm, and suicide. Military dermatologists, as well as other specialists, may be limited in the care they are able to provide due to manpower, staffing, demand, and institutional guidelines; however, to better serve those who serve in a holistic manner, consideration must be given to rethink what is “medically essential” and “cosmetic” and leverage the available skills, techniques, and equipment to increase the readiness of the force.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

The use of isotretinoin to treat acne was not associated with an increase in adverse neuropsychiatric outcomes, compared with the use of oral antibiotics, in a large retrospective cohort study published in the British Journal of Dermatology.

Although severe neuropsychiatric effects associated with isotretinoin therapy in patients with acne have been reported, “the evidence base ... is mixed and inconclusive,” and many studies are small, Seena Fazel, MBChB, MD, of the department of psychiatry, Oxford University, England, and co-authors write in the study.

The study results suggest that isotretinoin is conferring protection against adverse neuropsychiatric outcomes, particularly when compared with using oral antibiotics to treat acne, Dr. Fazel, professor of forensic psychiatry at Oxford University and the study’s senior author, said in an interview.

In the study, the investigators reviewed electronic health records (2013-2019) from a primarily United States–based dataset (TriNetX) of patients with acne aged 12-27 who had been followed for up to 1 year after their prescriptions had been dispensed.

There were four arms: those prescribed isotretinoin (30,866), oral antibiotics (44,748), topical anti-acne treatments (108,367), and those who had not been prescribed any acne treatment (78,666). The primary outcomes were diagnoses of a neuropsychiatric disorder (psychotic, mood, anxiety, personality, behavioral, and sleep disorders; and non-fatal self-harm) within one year of being prescribed treatment.

After using propensity score matching to adjust for confounders at baseline, the investigators determined that the odds ratio for any incident neuropsychiatric outcomes among patients with acne treated with isotretinoin was 0.80 (95% confidence interval, 0.74-0.87), compared with patients on oral antibiotics; 0.94 (95% CI, 0.87-1.02), compared with patients on topical anti-acne medications; and 1.06 (95% CI, 0.97-1.16), compared with those without a prescription for anti-acne medicines.

Side effects of isotretinoin – such as headache, dry mouth, and fatigue – were higher among those on isotretinoin than in the other three groups.

The authors concluded that isotretinoin was not independently linked to excess adverse neuropsychiatric outcomes at a population level. “We observed a consistent association between increasing acne severity as indicated by anti-acne treatment options and incidence of adverse neuropsychiatric outcomes, but the findings showed that isotretinoin exposure did not add to the risk of neuropsychiatric adverse outcomes over and above what was associated with oral antibiotics,” they write.

Isotretinoin treatment “appeared to mitigate the excess neuropsychiatric risk associated with recalcitrant moderate-to-severe acne,” they add.

The dermatology community has been interested in the impact isotretinoin has on mental health, and “I think clinically, they see that people get better on isotretinoin and their mental health improves,” Dr. Fazel told this news organization.

Asked to comment on the study results, John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, commended the investigators for the design of the trial.

“One of the strengths of this study is that they use a technique called propensity-score matching, where you try to make the groups of patients similar with respect to their other characteristics to minimize the risks of confounding and bias in the study, which I think is a real strength,” he told this news organization. “The other thing that they do, which I think is a strength, is to think about the impact of acne severity on these outcomes, because we know acne itself is associated with depression and risk for suicide and other neuropsychiatric outcomes.”

Including a cohort of patients who had acne and received oral antibiotics for comparison “is a nice way to address the potential for confounding by severity and confounding by indication,” Dr. Barbieri said. “Those who get antibiotics usually have more severe acne. They may not have it as severely as those who get isotretinoin, but it is a nice approach to account for background levels of depression and neuropsychiatric outcomes in patients with acne. I think that is a real strength of the study. This is one of the best studies to have looked at this question.” 

However, although the study found that isotretinoin decreased the excess psychiatric risk associated with refractory moderate-to-severe acne, it does not rule out the possibility that individuals may experience an adverse psychiatric outcome while on isotretinoin, Dr. Barbieri said.

“While I think on a population level, we absolutely can feel reassured by these data, I do think there are individual patients who have idiosyncratic, unpredictable reactions to isotretinoin where they have mood changes, whether it be irritability, depression, or other mood changes,” he cautioned. “Given the association of acne itself with mental health comorbidities, it is important to screen for comorbidities such as depression in all patients with acne.”

The study was funded by the Wellcome Trust, which provided Dr. Fazel and the first author with financial support for the study. One author is an employee of TriNetX; the other authors had no relevant disclosures. Dr. Barbieri reported no financial disclosures. He is cochair of the AAD’s Acne Guidelines Workgroup and associate editor at JAMA Dermatology.

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

The use of isotretinoin to treat acne was not associated with an increase in adverse neuropsychiatric outcomes, compared with the use of oral antibiotics, in a large retrospective cohort study published in the British Journal of Dermatology.

Although severe neuropsychiatric effects associated with isotretinoin therapy in patients with acne have been reported, “the evidence base ... is mixed and inconclusive,” and many studies are small, Seena Fazel, MBChB, MD, of the department of psychiatry, Oxford University, England, and co-authors write in the study.

The study results suggest that isotretinoin is conferring protection against adverse neuropsychiatric outcomes, particularly when compared with using oral antibiotics to treat acne, Dr. Fazel, professor of forensic psychiatry at Oxford University and the study’s senior author, said in an interview.

In the study, the investigators reviewed electronic health records (2013-2019) from a primarily United States–based dataset (TriNetX) of patients with acne aged 12-27 who had been followed for up to 1 year after their prescriptions had been dispensed.

There were four arms: those prescribed isotretinoin (30,866), oral antibiotics (44,748), topical anti-acne treatments (108,367), and those who had not been prescribed any acne treatment (78,666). The primary outcomes were diagnoses of a neuropsychiatric disorder (psychotic, mood, anxiety, personality, behavioral, and sleep disorders; and non-fatal self-harm) within one year of being prescribed treatment.

After using propensity score matching to adjust for confounders at baseline, the investigators determined that the odds ratio for any incident neuropsychiatric outcomes among patients with acne treated with isotretinoin was 0.80 (95% confidence interval, 0.74-0.87), compared with patients on oral antibiotics; 0.94 (95% CI, 0.87-1.02), compared with patients on topical anti-acne medications; and 1.06 (95% CI, 0.97-1.16), compared with those without a prescription for anti-acne medicines.

Side effects of isotretinoin – such as headache, dry mouth, and fatigue – were higher among those on isotretinoin than in the other three groups.

The authors concluded that isotretinoin was not independently linked to excess adverse neuropsychiatric outcomes at a population level. “We observed a consistent association between increasing acne severity as indicated by anti-acne treatment options and incidence of adverse neuropsychiatric outcomes, but the findings showed that isotretinoin exposure did not add to the risk of neuropsychiatric adverse outcomes over and above what was associated with oral antibiotics,” they write.

Isotretinoin treatment “appeared to mitigate the excess neuropsychiatric risk associated with recalcitrant moderate-to-severe acne,” they add.

The dermatology community has been interested in the impact isotretinoin has on mental health, and “I think clinically, they see that people get better on isotretinoin and their mental health improves,” Dr. Fazel told this news organization.

Asked to comment on the study results, John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, commended the investigators for the design of the trial.

“One of the strengths of this study is that they use a technique called propensity-score matching, where you try to make the groups of patients similar with respect to their other characteristics to minimize the risks of confounding and bias in the study, which I think is a real strength,” he told this news organization. “The other thing that they do, which I think is a strength, is to think about the impact of acne severity on these outcomes, because we know acne itself is associated with depression and risk for suicide and other neuropsychiatric outcomes.”

Including a cohort of patients who had acne and received oral antibiotics for comparison “is a nice way to address the potential for confounding by severity and confounding by indication,” Dr. Barbieri said. “Those who get antibiotics usually have more severe acne. They may not have it as severely as those who get isotretinoin, but it is a nice approach to account for background levels of depression and neuropsychiatric outcomes in patients with acne. I think that is a real strength of the study. This is one of the best studies to have looked at this question.” 

However, although the study found that isotretinoin decreased the excess psychiatric risk associated with refractory moderate-to-severe acne, it does not rule out the possibility that individuals may experience an adverse psychiatric outcome while on isotretinoin, Dr. Barbieri said.

“While I think on a population level, we absolutely can feel reassured by these data, I do think there are individual patients who have idiosyncratic, unpredictable reactions to isotretinoin where they have mood changes, whether it be irritability, depression, or other mood changes,” he cautioned. “Given the association of acne itself with mental health comorbidities, it is important to screen for comorbidities such as depression in all patients with acne.”

The study was funded by the Wellcome Trust, which provided Dr. Fazel and the first author with financial support for the study. One author is an employee of TriNetX; the other authors had no relevant disclosures. Dr. Barbieri reported no financial disclosures. He is cochair of the AAD’s Acne Guidelines Workgroup and associate editor at JAMA Dermatology.

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

The use of isotretinoin to treat acne was not associated with an increase in adverse neuropsychiatric outcomes, compared with the use of oral antibiotics, in a large retrospective cohort study published in the British Journal of Dermatology.

Although severe neuropsychiatric effects associated with isotretinoin therapy in patients with acne have been reported, “the evidence base ... is mixed and inconclusive,” and many studies are small, Seena Fazel, MBChB, MD, of the department of psychiatry, Oxford University, England, and co-authors write in the study.

The study results suggest that isotretinoin is conferring protection against adverse neuropsychiatric outcomes, particularly when compared with using oral antibiotics to treat acne, Dr. Fazel, professor of forensic psychiatry at Oxford University and the study’s senior author, said in an interview.

In the study, the investigators reviewed electronic health records (2013-2019) from a primarily United States–based dataset (TriNetX) of patients with acne aged 12-27 who had been followed for up to 1 year after their prescriptions had been dispensed.

There were four arms: those prescribed isotretinoin (30,866), oral antibiotics (44,748), topical anti-acne treatments (108,367), and those who had not been prescribed any acne treatment (78,666). The primary outcomes were diagnoses of a neuropsychiatric disorder (psychotic, mood, anxiety, personality, behavioral, and sleep disorders; and non-fatal self-harm) within one year of being prescribed treatment.

After using propensity score matching to adjust for confounders at baseline, the investigators determined that the odds ratio for any incident neuropsychiatric outcomes among patients with acne treated with isotretinoin was 0.80 (95% confidence interval, 0.74-0.87), compared with patients on oral antibiotics; 0.94 (95% CI, 0.87-1.02), compared with patients on topical anti-acne medications; and 1.06 (95% CI, 0.97-1.16), compared with those without a prescription for anti-acne medicines.

Side effects of isotretinoin – such as headache, dry mouth, and fatigue – were higher among those on isotretinoin than in the other three groups.

The authors concluded that isotretinoin was not independently linked to excess adverse neuropsychiatric outcomes at a population level. “We observed a consistent association between increasing acne severity as indicated by anti-acne treatment options and incidence of adverse neuropsychiatric outcomes, but the findings showed that isotretinoin exposure did not add to the risk of neuropsychiatric adverse outcomes over and above what was associated with oral antibiotics,” they write.

Isotretinoin treatment “appeared to mitigate the excess neuropsychiatric risk associated with recalcitrant moderate-to-severe acne,” they add.

The dermatology community has been interested in the impact isotretinoin has on mental health, and “I think clinically, they see that people get better on isotretinoin and their mental health improves,” Dr. Fazel told this news organization.

Asked to comment on the study results, John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, commended the investigators for the design of the trial.

“One of the strengths of this study is that they use a technique called propensity-score matching, where you try to make the groups of patients similar with respect to their other characteristics to minimize the risks of confounding and bias in the study, which I think is a real strength,” he told this news organization. “The other thing that they do, which I think is a strength, is to think about the impact of acne severity on these outcomes, because we know acne itself is associated with depression and risk for suicide and other neuropsychiatric outcomes.”

Including a cohort of patients who had acne and received oral antibiotics for comparison “is a nice way to address the potential for confounding by severity and confounding by indication,” Dr. Barbieri said. “Those who get antibiotics usually have more severe acne. They may not have it as severely as those who get isotretinoin, but it is a nice approach to account for background levels of depression and neuropsychiatric outcomes in patients with acne. I think that is a real strength of the study. This is one of the best studies to have looked at this question.” 

However, although the study found that isotretinoin decreased the excess psychiatric risk associated with refractory moderate-to-severe acne, it does not rule out the possibility that individuals may experience an adverse psychiatric outcome while on isotretinoin, Dr. Barbieri said.

“While I think on a population level, we absolutely can feel reassured by these data, I do think there are individual patients who have idiosyncratic, unpredictable reactions to isotretinoin where they have mood changes, whether it be irritability, depression, or other mood changes,” he cautioned. “Given the association of acne itself with mental health comorbidities, it is important to screen for comorbidities such as depression in all patients with acne.”

The study was funded by the Wellcome Trust, which provided Dr. Fazel and the first author with financial support for the study. One author is an employee of TriNetX; the other authors had no relevant disclosures. Dr. Barbieri reported no financial disclosures. He is cochair of the AAD’s Acne Guidelines Workgroup and associate editor at JAMA Dermatology.

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

My inspiration to write about cupping this month stems from the perception that everyone seems to be talking about it, from a facialist who suggested it for me to a coworker who swears by cupping to treat her allergies. Cupping is by no means a novel procedure. Its use as a health therapy dates back thousands of years to ancient Egypt (1500 BCE), ancient Greece (described by Hippocrates), ancient Rome (described by the Greek physician Galen), China (during the Han dynasty, 206 BCE to 220 CE) and traditional Islamic culture.¹ Over the past decade, the popularity of this ancient procedure has been increasing in the United States.¹ Cupping has been applied as a remedy for various dermatologic and medical conditions, including herpes zoster, headaches, diminished appetite, maldigestion, abscess evacuation, narcolepsy, pain, fever, dysmenorrhea, and gout.^1,2

Theories on the mechanism(s) of action

The practice of cupping is differentiated into dry and wet cupping.^1,2 Traditionally, with dry cupping, a flame is applied to heat the air inside a thick glass cup (rather than the cup itself).¹ The cup is placed on the skin surface, and negative pressure suctions the skin into the cup. Wet cupping differs mainly from dry cupping in that it involves blood-letting. Cups made of either silicone or glass of varying size and shapes are used. Modern adaptations to cupping include needle, herbal, and pulsatile cupping, as well as a “moving cupping” technique (vs. traditionally stationary cups).¹

Thinkstock

There are several theories, many of which are derived from the nondermatologic literature (that is, pain management), as to how cupping may deliver a clinical benefit. Some theories are based in scientific and medical principles, whereas other theories are more whimsical – specifically, that cupping draws out evil spirits.² Studies of dry cupping have suggested that the procedure results in increased oxygenation of muscles via a local increase in oxygenated hemoglobin, which may help improve muscular activity and reduce pain.¹ As theorized by Lowe in 2017, negative pressure exerted by dry cupping leads to stretching and dilation of capillaries, which increases blood flow.³ Wet cupping has been shown to increase heat shock protein 70 (HSP70) and beta-endorphin expression in rat models, which is thought to facilitate pain management.1 Removal of oxidants and reduction of reactive oxygen species in the blood is believed to be among the benefits of wet cupping.¹
 

Cupping in general dermatology

While cupping has been used to treat a wide array of medical conditions, the ancient practice has been utilized in dermatology as a therapy mainly for herpes zoster and associated postherpetic neuralgia, as well as various inflammatory conditions.

Herpes zoster

In 2010, Cao et al. reported on their systematic review of wet cupping after completing searches of multiple databases (that is, PubMed, the Cochrane Library [Issue 3, 2008], China Network Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database). They identified eight randomized controlled trials involving 651 patients, with meta-analyses revealing that wet cupping performed better than medications in terms of the number of “cured” patients, number of patients with improved symptoms, and a lower incidence of postherpetic neuralgia. Wet cupping, in addition to medication, was also found to be superior to medication alone in multiple patients. The researchers concluded that wet cupping appears to effectively treat herpes zoster.⁴ However, the study failed to identify which medications were used to treat herpes zoster. In the United States, common medications for herpes zoster include acyclovir, valacyclovir, steroids, gabapentin, and other neuromodulators. Without knowing which medications were used, it is difficult to compare cupping to medication in terms of efficacy in treating herpes zoster.

Urticaria

Urticaria (hives) is an inflammatory skin condition that can be very uncomfortable for patients but often resolves without intervention within several months after onset. In 2001, Li and Ding reported on the treatment with cupping of 40 patients with urticaria. The cure rate among the treatment group was cited as 55%, compared with 30% in the control group, who were treated with a traditional Chinese remedy and an unidentified first-generation antihistamine.^1,5 In 2020, Xiao et al. conducted a systematic review and meta-analysis of cupping therapy for patients with chronic urticaria. They identified 13 comparisons from 12 randomized controlled trials involving 842 subjects. The investigators found no significant differences between wet cupping and medication usage. They also found that cupping combined with antihistamine treatment was superior to antihistamines alone, and cupping therapy with acupuncture was more effective than acupuncture alone. The investigators did call for caution, citing the poor quality of the studies reviewed.⁶

It is important to note that it is difficult to attribute resolution of urticaria to the use of cupping given the self-resolution often associated with this condition. Antihistamines are the mainstay of therapy for urticaria, but in my personal experience, patients are not entirely satisfied with the level of symptom control with antihistamines alone and often search for alternative therapies to control the pesky hives and associated itch. In 2014, omalizumab (Xolair) was approved for treating chronic idiopathic urticaria, which has helped patients control symptoms of chronic idiopathic urticaria without needing to take antihistamines. There was no indication that the studies reviewed by Xiao et al. compared cupping against this new effective treatment. Therefore, these studies comparing cupping to medical management are outdated.

Acne, eczema, and psoriasis

Soliman’s 2018 review of cupping in dermatology included a few studies on these common cutaneous conditions. For instance, a 2013 single-blind prospective study by Xu et al. reported on the results of patients with moderate acne who received wet cupping (in the form of prickling bloodletting) twice weekly for 6 weeks.⁷ They reported that patients demonstrated improvement in the global acne grading system (GAGS) score by the end of the trial.^1,7 Unfortunately, cupping was not compared with standard acne treatments (that is, benzoyl peroxide, topical and oral antibiotics, isotretinoin, topical retinoids, spironolactone).

In evaluating cupping for acute eczema, wet cupping was compared with oral loratadine and topical ointments in a 2007 study by Yao and Li. They divided 88 cases into treatment and control groups, with the former group (n = 46) receiving bloodletting puncturing and cupping and the control group (n = 42) receiving oral loratadine and topical Pairuisong (an herbal ointment used in Chinese medicine). The investigators observed no significant difference in total effective rates but a superior difference in the rates of responses that were considered “cured” and “markedly effective” in favor of the cupping treatment.^1,8 However, a case report by Hon et al. has indicated that cupping therapy may be associated with more harm than benefit when used as an eczema treatment.^1,9

In addition, it is important to note that the past 5 years have been gamechanging in the management of chronic eczema in terms of the array of novel and effective therapies (e.g., dupilumab and JAK inhibitors) and chronic moderate-to-severe eczema has become very treatable. Similarly, acute eczema is often successfully managed with topical steroids, calcineurin inhibitors, and emollients. As such, there is no compelling reason to consider an unproven treatment such as cupping.

In 2020, Xing et al. reviewed 16 randomized controlled trials assessing the use of “moving cupping” for plaque psoriasis, with 1,164 patients meeting inclusion criteria. Moving cupping was found to be significantly more effective than “no-moving” cupping therapy, and moving cupping, combined with medications, performed better than medications alone.¹⁰ None of the trials evaluated in this study included randomized controlled trials that compared patients using any of the more modern psoriasis medications, specifically biologics. And, again, the studies evaluated were not of the highest quality.

The data that support cupping, as summarized above, are based mostly on case reports, and strong double-blind prospective studies are lacking. Additionally, most of the studies cited gauged the efficacy of cupping using qualitative endpoints, rather than standardized quantitative endpoints and scales. Moreover, spontaneous remission of various dermatoses can occur, or they can improve over time, including acute eczema, psoriasis, and, especially, urticaria.
 

Adverse effects of cupping

Often alternative therapies are seen as “benign” and without adverse effects. However, complications can result from cupping. Trauma can be induced from the cupping itself by damaging superficial blood vessels and causing bruising.^1,11 Blistering can also occur secondary to the suction effect, and the epidermal and dermal layers of the skin can be separated.^1,11 Further, burns and discoloration have also been noted secondary to heat, trauma, and post inflammatory pigmentary changes.^1,11 Another risk of cupping is the Koebner phenomenon, which occurs with psoriasis, with new lesions appearing in traumatized skin.¹² Other adverse outcomes that have been reported with cupping include reactivation of herpes simplex virus secondary to skin trauma, iron deficiency anemia (secondary to blood loss), panniculitis, infections, and residual marks mistaken for signs of child abuse.^1,11

Cupping in aesthetic dermatology

Facial cupping, a distinct practice from body cupping used to treat general dermatology conditions described previously, is also increasing in popularity. This practice is usually conducted in association with a facial or facial acupuncture by an aesthetician or other licensed professional. It can also be performed using at-home kits. The marketing claims for facial cupping cite improved tightening and contouring of facial skin, increased facial microcirculation and collagen synthesis, and enhanced lymphatic flow to aid with facial puffiness or swelling. One supposed mechanism for these benefits is that cupping increases blood flow. Interestingly, there was a 2020 animal study in which photoacoustic imaging of a mouse ear revealed increased temporary blood flow in the cupping microenvironment.¹³ Currently, however, there is no evidence in the English scientific literature that supports facial cupping. The benefits attributed to facial cupping for aesthetic purposes have emerged only in personal anecdotes. The temporary increase in blood flow may induce inflammation and swelling that adds volume to the face and temporarily diminishes wrinkles. However, this temporary plumpness may be associated with adverse effects, such as local trauma, irritation, bruising, postinflammatory pigmentary alteration, or even herpes reactivation. In my opinion, the possible adverse effects of cupping outweigh any potential benefit, especially given the insufficient evidence supporting the utility of cupping for cosmetic enhancement.

Summary

There is increasing interest among patients to incorporate complementary and alternative medicine – including the ancient tradition of cupping – in managing medical dermatologic conditions. However, current evidence supporting cupping as an effective therapeutic strategy is not strong, with most studies to date appearing to be of poor quality or not sufficiently convincing to displace standard therapies. Our medical strategies for managing chronic dermatologic conditions, particularly inflammatory disorders, continue to improve from both a safety and a proven efficacy standpoint. Therefore, I would not forgo medical management in favor of cupping. While cupping can be used as an adjunct therapy, I would caution patients about possible adverse side effects. In the aesthetic world, cupping is also gaining popularity, but this trend is also not supported by current evidence or studies, at least in the Western literature.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Write to her at dermnews@mdedge.com or message her on Instragram @DrChloeGoldman. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other disclosures.

References

1. Soliman Y et al. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Jun;27(2):103-7.

2. França K and Lotti T. Advances in Integrative Dermatology. John Wiley & Sons, 2019.

3. Lowe DT. Complement Ther Clin Pract. 2017 Nov;29:162-8.

4.Cao H et al. Altern Ther Health Med. 2010 Nov-Dec;16(6):48-54.

5. Li L and Ding J. J Tradit Chin Med. 2001 Mar;21(1):37-8.

6. Xiao XJ et al. J Integr Med. 2020 Jul;18(4):303-12.

7. Xu J et al. J Tradit Chin Med. 2013 Dec;33(6):752-6.

8. Yao J et al. Zhongguo Zhen Jiu. 2007; Jun;27(6):424-6.

9. Hon KL et al. Case Rep Pediatr. 2013;2013:605829.

10. Xing M et al. Medicine (Baltimore). 2020 Oct 9;99(41):e22539.

11. Kim TH et al. Eur J Integr Med. 2014 Aug 1;6(4):434-40.

12. Vender R and Vender R. J Cutan Med Surg. 2015 May-Jun;19(3):320-2.

13. Zhou Y et al. Biomed Opt Express. 2020 Apr 6;11(5):2394-401.

This article was updated 4/25/22.

My inspiration to write about cupping this month stems from the perception that everyone seems to be talking about it, from a facialist who suggested it for me to a coworker who swears by cupping to treat her allergies. Cupping is by no means a novel procedure. Its use as a health therapy dates back thousands of years to ancient Egypt (1500 BCE), ancient Greece (described by Hippocrates), ancient Rome (described by the Greek physician Galen), China (during the Han dynasty, 206 BCE to 220 CE) and traditional Islamic culture.¹ Over the past decade, the popularity of this ancient procedure has been increasing in the United States.¹ Cupping has been applied as a remedy for various dermatologic and medical conditions, including herpes zoster, headaches, diminished appetite, maldigestion, abscess evacuation, narcolepsy, pain, fever, dysmenorrhea, and gout.^1,2

Theories on the mechanism(s) of action

The practice of cupping is differentiated into dry and wet cupping.^1,2 Traditionally, with dry cupping, a flame is applied to heat the air inside a thick glass cup (rather than the cup itself).¹ The cup is placed on the skin surface, and negative pressure suctions the skin into the cup. Wet cupping differs mainly from dry cupping in that it involves blood-letting. Cups made of either silicone or glass of varying size and shapes are used. Modern adaptations to cupping include needle, herbal, and pulsatile cupping, as well as a “moving cupping” technique (vs. traditionally stationary cups).¹

Thinkstock

There are several theories, many of which are derived from the nondermatologic literature (that is, pain management), as to how cupping may deliver a clinical benefit. Some theories are based in scientific and medical principles, whereas other theories are more whimsical – specifically, that cupping draws out evil spirits.² Studies of dry cupping have suggested that the procedure results in increased oxygenation of muscles via a local increase in oxygenated hemoglobin, which may help improve muscular activity and reduce pain.¹ As theorized by Lowe in 2017, negative pressure exerted by dry cupping leads to stretching and dilation of capillaries, which increases blood flow.³ Wet cupping has been shown to increase heat shock protein 70 (HSP70) and beta-endorphin expression in rat models, which is thought to facilitate pain management.1 Removal of oxidants and reduction of reactive oxygen species in the blood is believed to be among the benefits of wet cupping.¹
 

Cupping in general dermatology

While cupping has been used to treat a wide array of medical conditions, the ancient practice has been utilized in dermatology as a therapy mainly for herpes zoster and associated postherpetic neuralgia, as well as various inflammatory conditions.

Herpes zoster

In 2010, Cao et al. reported on their systematic review of wet cupping after completing searches of multiple databases (that is, PubMed, the Cochrane Library [Issue 3, 2008], China Network Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database). They identified eight randomized controlled trials involving 651 patients, with meta-analyses revealing that wet cupping performed better than medications in terms of the number of “cured” patients, number of patients with improved symptoms, and a lower incidence of postherpetic neuralgia. Wet cupping, in addition to medication, was also found to be superior to medication alone in multiple patients. The researchers concluded that wet cupping appears to effectively treat herpes zoster.⁴ However, the study failed to identify which medications were used to treat herpes zoster. In the United States, common medications for herpes zoster include acyclovir, valacyclovir, steroids, gabapentin, and other neuromodulators. Without knowing which medications were used, it is difficult to compare cupping to medication in terms of efficacy in treating herpes zoster.

Urticaria

Urticaria (hives) is an inflammatory skin condition that can be very uncomfortable for patients but often resolves without intervention within several months after onset. In 2001, Li and Ding reported on the treatment with cupping of 40 patients with urticaria. The cure rate among the treatment group was cited as 55%, compared with 30% in the control group, who were treated with a traditional Chinese remedy and an unidentified first-generation antihistamine.^1,5 In 2020, Xiao et al. conducted a systematic review and meta-analysis of cupping therapy for patients with chronic urticaria. They identified 13 comparisons from 12 randomized controlled trials involving 842 subjects. The investigators found no significant differences between wet cupping and medication usage. They also found that cupping combined with antihistamine treatment was superior to antihistamines alone, and cupping therapy with acupuncture was more effective than acupuncture alone. The investigators did call for caution, citing the poor quality of the studies reviewed.⁶

It is important to note that it is difficult to attribute resolution of urticaria to the use of cupping given the self-resolution often associated with this condition. Antihistamines are the mainstay of therapy for urticaria, but in my personal experience, patients are not entirely satisfied with the level of symptom control with antihistamines alone and often search for alternative therapies to control the pesky hives and associated itch. In 2014, omalizumab (Xolair) was approved for treating chronic idiopathic urticaria, which has helped patients control symptoms of chronic idiopathic urticaria without needing to take antihistamines. There was no indication that the studies reviewed by Xiao et al. compared cupping against this new effective treatment. Therefore, these studies comparing cupping to medical management are outdated.

Acne, eczema, and psoriasis

Soliman’s 2018 review of cupping in dermatology included a few studies on these common cutaneous conditions. For instance, a 2013 single-blind prospective study by Xu et al. reported on the results of patients with moderate acne who received wet cupping (in the form of prickling bloodletting) twice weekly for 6 weeks.⁷ They reported that patients demonstrated improvement in the global acne grading system (GAGS) score by the end of the trial.^1,7 Unfortunately, cupping was not compared with standard acne treatments (that is, benzoyl peroxide, topical and oral antibiotics, isotretinoin, topical retinoids, spironolactone).

In evaluating cupping for acute eczema, wet cupping was compared with oral loratadine and topical ointments in a 2007 study by Yao and Li. They divided 88 cases into treatment and control groups, with the former group (n = 46) receiving bloodletting puncturing and cupping and the control group (n = 42) receiving oral loratadine and topical Pairuisong (an herbal ointment used in Chinese medicine). The investigators observed no significant difference in total effective rates but a superior difference in the rates of responses that were considered “cured” and “markedly effective” in favor of the cupping treatment.^1,8 However, a case report by Hon et al. has indicated that cupping therapy may be associated with more harm than benefit when used as an eczema treatment.^1,9

In addition, it is important to note that the past 5 years have been gamechanging in the management of chronic eczema in terms of the array of novel and effective therapies (e.g., dupilumab and JAK inhibitors) and chronic moderate-to-severe eczema has become very treatable. Similarly, acute eczema is often successfully managed with topical steroids, calcineurin inhibitors, and emollients. As such, there is no compelling reason to consider an unproven treatment such as cupping.

In 2020, Xing et al. reviewed 16 randomized controlled trials assessing the use of “moving cupping” for plaque psoriasis, with 1,164 patients meeting inclusion criteria. Moving cupping was found to be significantly more effective than “no-moving” cupping therapy, and moving cupping, combined with medications, performed better than medications alone.¹⁰ None of the trials evaluated in this study included randomized controlled trials that compared patients using any of the more modern psoriasis medications, specifically biologics. And, again, the studies evaluated were not of the highest quality.

The data that support cupping, as summarized above, are based mostly on case reports, and strong double-blind prospective studies are lacking. Additionally, most of the studies cited gauged the efficacy of cupping using qualitative endpoints, rather than standardized quantitative endpoints and scales. Moreover, spontaneous remission of various dermatoses can occur, or they can improve over time, including acute eczema, psoriasis, and, especially, urticaria.
 

Adverse effects of cupping

Often alternative therapies are seen as “benign” and without adverse effects. However, complications can result from cupping. Trauma can be induced from the cupping itself by damaging superficial blood vessels and causing bruising.^1,11 Blistering can also occur secondary to the suction effect, and the epidermal and dermal layers of the skin can be separated.^1,11 Further, burns and discoloration have also been noted secondary to heat, trauma, and post inflammatory pigmentary changes.^1,11 Another risk of cupping is the Koebner phenomenon, which occurs with psoriasis, with new lesions appearing in traumatized skin.¹² Other adverse outcomes that have been reported with cupping include reactivation of herpes simplex virus secondary to skin trauma, iron deficiency anemia (secondary to blood loss), panniculitis, infections, and residual marks mistaken for signs of child abuse.^1,11

Cupping in aesthetic dermatology

Facial cupping, a distinct practice from body cupping used to treat general dermatology conditions described previously, is also increasing in popularity. This practice is usually conducted in association with a facial or facial acupuncture by an aesthetician or other licensed professional. It can also be performed using at-home kits. The marketing claims for facial cupping cite improved tightening and contouring of facial skin, increased facial microcirculation and collagen synthesis, and enhanced lymphatic flow to aid with facial puffiness or swelling. One supposed mechanism for these benefits is that cupping increases blood flow. Interestingly, there was a 2020 animal study in which photoacoustic imaging of a mouse ear revealed increased temporary blood flow in the cupping microenvironment.¹³ Currently, however, there is no evidence in the English scientific literature that supports facial cupping. The benefits attributed to facial cupping for aesthetic purposes have emerged only in personal anecdotes. The temporary increase in blood flow may induce inflammation and swelling that adds volume to the face and temporarily diminishes wrinkles. However, this temporary plumpness may be associated with adverse effects, such as local trauma, irritation, bruising, postinflammatory pigmentary alteration, or even herpes reactivation. In my opinion, the possible adverse effects of cupping outweigh any potential benefit, especially given the insufficient evidence supporting the utility of cupping for cosmetic enhancement.

Summary

There is increasing interest among patients to incorporate complementary and alternative medicine – including the ancient tradition of cupping – in managing medical dermatologic conditions. However, current evidence supporting cupping as an effective therapeutic strategy is not strong, with most studies to date appearing to be of poor quality or not sufficiently convincing to displace standard therapies. Our medical strategies for managing chronic dermatologic conditions, particularly inflammatory disorders, continue to improve from both a safety and a proven efficacy standpoint. Therefore, I would not forgo medical management in favor of cupping. While cupping can be used as an adjunct therapy, I would caution patients about possible adverse side effects. In the aesthetic world, cupping is also gaining popularity, but this trend is also not supported by current evidence or studies, at least in the Western literature.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Write to her at dermnews@mdedge.com or message her on Instragram @DrChloeGoldman. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other disclosures.

References

1. Soliman Y et al. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Jun;27(2):103-7.

2. França K and Lotti T. Advances in Integrative Dermatology. John Wiley & Sons, 2019.

3. Lowe DT. Complement Ther Clin Pract. 2017 Nov;29:162-8.

4.Cao H et al. Altern Ther Health Med. 2010 Nov-Dec;16(6):48-54.

5. Li L and Ding J. J Tradit Chin Med. 2001 Mar;21(1):37-8.

6. Xiao XJ et al. J Integr Med. 2020 Jul;18(4):303-12.

7. Xu J et al. J Tradit Chin Med. 2013 Dec;33(6):752-6.

8. Yao J et al. Zhongguo Zhen Jiu. 2007; Jun;27(6):424-6.

9. Hon KL et al. Case Rep Pediatr. 2013;2013:605829.

10. Xing M et al. Medicine (Baltimore). 2020 Oct 9;99(41):e22539.

11. Kim TH et al. Eur J Integr Med. 2014 Aug 1;6(4):434-40.

12. Vender R and Vender R. J Cutan Med Surg. 2015 May-Jun;19(3):320-2.

13. Zhou Y et al. Biomed Opt Express. 2020 Apr 6;11(5):2394-401.

This article was updated 4/25/22.

My inspiration to write about cupping this month stems from the perception that everyone seems to be talking about it, from a facialist who suggested it for me to a coworker who swears by cupping to treat her allergies. Cupping is by no means a novel procedure. Its use as a health therapy dates back thousands of years to ancient Egypt (1500 BCE), ancient Greece (described by Hippocrates), ancient Rome (described by the Greek physician Galen), China (during the Han dynasty, 206 BCE to 220 CE) and traditional Islamic culture.¹ Over the past decade, the popularity of this ancient procedure has been increasing in the United States.¹ Cupping has been applied as a remedy for various dermatologic and medical conditions, including herpes zoster, headaches, diminished appetite, maldigestion, abscess evacuation, narcolepsy, pain, fever, dysmenorrhea, and gout.^1,2

Theories on the mechanism(s) of action

The practice of cupping is differentiated into dry and wet cupping.^1,2 Traditionally, with dry cupping, a flame is applied to heat the air inside a thick glass cup (rather than the cup itself).¹ The cup is placed on the skin surface, and negative pressure suctions the skin into the cup. Wet cupping differs mainly from dry cupping in that it involves blood-letting. Cups made of either silicone or glass of varying size and shapes are used. Modern adaptations to cupping include needle, herbal, and pulsatile cupping, as well as a “moving cupping” technique (vs. traditionally stationary cups).¹

Thinkstock

There are several theories, many of which are derived from the nondermatologic literature (that is, pain management), as to how cupping may deliver a clinical benefit. Some theories are based in scientific and medical principles, whereas other theories are more whimsical – specifically, that cupping draws out evil spirits.² Studies of dry cupping have suggested that the procedure results in increased oxygenation of muscles via a local increase in oxygenated hemoglobin, which may help improve muscular activity and reduce pain.¹ As theorized by Lowe in 2017, negative pressure exerted by dry cupping leads to stretching and dilation of capillaries, which increases blood flow.³ Wet cupping has been shown to increase heat shock protein 70 (HSP70) and beta-endorphin expression in rat models, which is thought to facilitate pain management.1 Removal of oxidants and reduction of reactive oxygen species in the blood is believed to be among the benefits of wet cupping.¹
 

Cupping in general dermatology

While cupping has been used to treat a wide array of medical conditions, the ancient practice has been utilized in dermatology as a therapy mainly for herpes zoster and associated postherpetic neuralgia, as well as various inflammatory conditions.

Herpes zoster

In 2010, Cao et al. reported on their systematic review of wet cupping after completing searches of multiple databases (that is, PubMed, the Cochrane Library [Issue 3, 2008], China Network Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database). They identified eight randomized controlled trials involving 651 patients, with meta-analyses revealing that wet cupping performed better than medications in terms of the number of “cured” patients, number of patients with improved symptoms, and a lower incidence of postherpetic neuralgia. Wet cupping, in addition to medication, was also found to be superior to medication alone in multiple patients. The researchers concluded that wet cupping appears to effectively treat herpes zoster.⁴ However, the study failed to identify which medications were used to treat herpes zoster. In the United States, common medications for herpes zoster include acyclovir, valacyclovir, steroids, gabapentin, and other neuromodulators. Without knowing which medications were used, it is difficult to compare cupping to medication in terms of efficacy in treating herpes zoster.

Urticaria

Urticaria (hives) is an inflammatory skin condition that can be very uncomfortable for patients but often resolves without intervention within several months after onset. In 2001, Li and Ding reported on the treatment with cupping of 40 patients with urticaria. The cure rate among the treatment group was cited as 55%, compared with 30% in the control group, who were treated with a traditional Chinese remedy and an unidentified first-generation antihistamine.^1,5 In 2020, Xiao et al. conducted a systematic review and meta-analysis of cupping therapy for patients with chronic urticaria. They identified 13 comparisons from 12 randomized controlled trials involving 842 subjects. The investigators found no significant differences between wet cupping and medication usage. They also found that cupping combined with antihistamine treatment was superior to antihistamines alone, and cupping therapy with acupuncture was more effective than acupuncture alone. The investigators did call for caution, citing the poor quality of the studies reviewed.⁶

It is important to note that it is difficult to attribute resolution of urticaria to the use of cupping given the self-resolution often associated with this condition. Antihistamines are the mainstay of therapy for urticaria, but in my personal experience, patients are not entirely satisfied with the level of symptom control with antihistamines alone and often search for alternative therapies to control the pesky hives and associated itch. In 2014, omalizumab (Xolair) was approved for treating chronic idiopathic urticaria, which has helped patients control symptoms of chronic idiopathic urticaria without needing to take antihistamines. There was no indication that the studies reviewed by Xiao et al. compared cupping against this new effective treatment. Therefore, these studies comparing cupping to medical management are outdated.

Acne, eczema, and psoriasis

Soliman’s 2018 review of cupping in dermatology included a few studies on these common cutaneous conditions. For instance, a 2013 single-blind prospective study by Xu et al. reported on the results of patients with moderate acne who received wet cupping (in the form of prickling bloodletting) twice weekly for 6 weeks.⁷ They reported that patients demonstrated improvement in the global acne grading system (GAGS) score by the end of the trial.^1,7 Unfortunately, cupping was not compared with standard acne treatments (that is, benzoyl peroxide, topical and oral antibiotics, isotretinoin, topical retinoids, spironolactone).

In evaluating cupping for acute eczema, wet cupping was compared with oral loratadine and topical ointments in a 2007 study by Yao and Li. They divided 88 cases into treatment and control groups, with the former group (n = 46) receiving bloodletting puncturing and cupping and the control group (n = 42) receiving oral loratadine and topical Pairuisong (an herbal ointment used in Chinese medicine). The investigators observed no significant difference in total effective rates but a superior difference in the rates of responses that were considered “cured” and “markedly effective” in favor of the cupping treatment.^1,8 However, a case report by Hon et al. has indicated that cupping therapy may be associated with more harm than benefit when used as an eczema treatment.^1,9

In addition, it is important to note that the past 5 years have been gamechanging in the management of chronic eczema in terms of the array of novel and effective therapies (e.g., dupilumab and JAK inhibitors) and chronic moderate-to-severe eczema has become very treatable. Similarly, acute eczema is often successfully managed with topical steroids, calcineurin inhibitors, and emollients. As such, there is no compelling reason to consider an unproven treatment such as cupping.

In 2020, Xing et al. reviewed 16 randomized controlled trials assessing the use of “moving cupping” for plaque psoriasis, with 1,164 patients meeting inclusion criteria. Moving cupping was found to be significantly more effective than “no-moving” cupping therapy, and moving cupping, combined with medications, performed better than medications alone.¹⁰ None of the trials evaluated in this study included randomized controlled trials that compared patients using any of the more modern psoriasis medications, specifically biologics. And, again, the studies evaluated were not of the highest quality.

The data that support cupping, as summarized above, are based mostly on case reports, and strong double-blind prospective studies are lacking. Additionally, most of the studies cited gauged the efficacy of cupping using qualitative endpoints, rather than standardized quantitative endpoints and scales. Moreover, spontaneous remission of various dermatoses can occur, or they can improve over time, including acute eczema, psoriasis, and, especially, urticaria.
 

Adverse effects of cupping

Often alternative therapies are seen as “benign” and without adverse effects. However, complications can result from cupping. Trauma can be induced from the cupping itself by damaging superficial blood vessels and causing bruising.^1,11 Blistering can also occur secondary to the suction effect, and the epidermal and dermal layers of the skin can be separated.^1,11 Further, burns and discoloration have also been noted secondary to heat, trauma, and post inflammatory pigmentary changes.^1,11 Another risk of cupping is the Koebner phenomenon, which occurs with psoriasis, with new lesions appearing in traumatized skin.¹² Other adverse outcomes that have been reported with cupping include reactivation of herpes simplex virus secondary to skin trauma, iron deficiency anemia (secondary to blood loss), panniculitis, infections, and residual marks mistaken for signs of child abuse.^1,11

Cupping in aesthetic dermatology

Facial cupping, a distinct practice from body cupping used to treat general dermatology conditions described previously, is also increasing in popularity. This practice is usually conducted in association with a facial or facial acupuncture by an aesthetician or other licensed professional. It can also be performed using at-home kits. The marketing claims for facial cupping cite improved tightening and contouring of facial skin, increased facial microcirculation and collagen synthesis, and enhanced lymphatic flow to aid with facial puffiness or swelling. One supposed mechanism for these benefits is that cupping increases blood flow. Interestingly, there was a 2020 animal study in which photoacoustic imaging of a mouse ear revealed increased temporary blood flow in the cupping microenvironment.¹³ Currently, however, there is no evidence in the English scientific literature that supports facial cupping. The benefits attributed to facial cupping for aesthetic purposes have emerged only in personal anecdotes. The temporary increase in blood flow may induce inflammation and swelling that adds volume to the face and temporarily diminishes wrinkles. However, this temporary plumpness may be associated with adverse effects, such as local trauma, irritation, bruising, postinflammatory pigmentary alteration, or even herpes reactivation. In my opinion, the possible adverse effects of cupping outweigh any potential benefit, especially given the insufficient evidence supporting the utility of cupping for cosmetic enhancement.

Summary

There is increasing interest among patients to incorporate complementary and alternative medicine – including the ancient tradition of cupping – in managing medical dermatologic conditions. However, current evidence supporting cupping as an effective therapeutic strategy is not strong, with most studies to date appearing to be of poor quality or not sufficiently convincing to displace standard therapies. Our medical strategies for managing chronic dermatologic conditions, particularly inflammatory disorders, continue to improve from both a safety and a proven efficacy standpoint. Therefore, I would not forgo medical management in favor of cupping. While cupping can be used as an adjunct therapy, I would caution patients about possible adverse side effects. In the aesthetic world, cupping is also gaining popularity, but this trend is also not supported by current evidence or studies, at least in the Western literature.

Dr. Goldman is a dermatologist in private practice in Miami and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a general dermatology practice. Write to her at dermnews@mdedge.com or message her on Instragram @DrChloeGoldman. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other disclosures.

References

1. Soliman Y et al. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Jun;27(2):103-7.

2. França K and Lotti T. Advances in Integrative Dermatology. John Wiley & Sons, 2019.

3. Lowe DT. Complement Ther Clin Pract. 2017 Nov;29:162-8.

4.Cao H et al. Altern Ther Health Med. 2010 Nov-Dec;16(6):48-54.

5. Li L and Ding J. J Tradit Chin Med. 2001 Mar;21(1):37-8.

6. Xiao XJ et al. J Integr Med. 2020 Jul;18(4):303-12.

7. Xu J et al. J Tradit Chin Med. 2013 Dec;33(6):752-6.

8. Yao J et al. Zhongguo Zhen Jiu. 2007; Jun;27(6):424-6.

9. Hon KL et al. Case Rep Pediatr. 2013;2013:605829.

10. Xing M et al. Medicine (Baltimore). 2020 Oct 9;99(41):e22539.

11. Kim TH et al. Eur J Integr Med. 2014 Aug 1;6(4):434-40.

12. Vender R and Vender R. J Cutan Med Surg. 2015 May-Jun;19(3):320-2.

13. Zhou Y et al. Biomed Opt Express. 2020 Apr 6;11(5):2394-401.

This article was updated 4/25/22.

Isotretinoin is one of the most highly regulated dermatologic medications on the market. The main reason for regulation through the US Food and Drug Administration (FDA)–managed iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) is to minimize the drug’s teratogenic potential, as isotretinoin can cause profound birth defects. The program originally categorized patients into 1 of 3 categories: (1) females of reproductive potential, (2) females not of reproductive potential, and (3) males. Unless the patient commits to abstinence, the program required female patients of childbearing potential to be on 2 forms of birth control and undergo regular pregnancy testing before obtaining refills. Over the last few years, the American Academy of Dermatology Association (AADA) has been advocating for changes to the iPLEDGE system. Proposed changes have included decreasing attestation frequency for patients who cannot get pregnant, increasing contraception counseling and options, and changing enrollment guidelines to encompass all gender and sexual minorities. As of December 13, 2021, the iPLEDGE system changed enrollment categories to reflect the AADA’s wishes and rolled out gender-neutral categories for enrollment in iPLEDGE. This change will simplify and enhance patients’ experience when starting isotretinoin.

Developing Inclusive iPLEDGE Categories

In recent years, dermatologists and patients have viewed these strict gender-based categories as limiting and problematic, especially for their transgender patients and female patients of childbearing potential who exclusively engage in intercourse with cisgender females. The United States has more than 10 million LGBTQIA+ citizens and an estimated 1.4 million adults who identify as transgender individuals, rendering the previously established gender-binary iPLEDGE categories outdated.^1,2

As a result, over the last few years, dermatologists, LGBTQIA+ allies, and patients have urged the FDA to create a gender-neutral registration process for iPLEDGE. With support from the AADA, the new modifications were approved for implementation and include 2 risk categories: (1) people who can get pregnant and (2) people who cannot get pregnant.³

As exciting as these changes are for the future of dermatologic practice, the actual transition to the new iPLEDGE system was described as a “failure, chaotic, and a disaster” due to additional changes made at the same time.⁴ The iPLEDGE system was switched to a new website administered by a different vendor and required providers to confirm each patient online by December 13, 2021. In addition, the new system required pharmacists to obtain risk management authorization via the iPLEDGE REMS website or by calling the iPLEDGE REMS center before dispensing isotretinoin. This overhaul did not work as planned, as the new website was constantly down and it was nearly impossible to reach a contact over the telephone. The complications resulted in major disruptions and delayed prescriptions for thousands of patients nationwide as well as a great disruption in workflow for physicians and pharmacists. The AADA subsequently met with the Isotretinoin Products Manufacturers Group to create workable solutions for these issues.

On January 14, 2022, the FDA posted updates regarding access to the iPLEDGE system. They have worked with the Isotretinoin Products Manufacturers Group to create workable solutions for patients and physicians while transferring the patients’ information to the new database. Their solution includes allowing physicians to send patients login links through their email to access their account instead of waiting for the call center. The majority of iPLEDGE users now have access to their accounts without issues, and the gender-neutral guidelines have been in place since the original change.

Impact of iPLEDGE Categories on Transgender Patients

These changes specifically will improve the experience of transgender men and cisgender women who are at no risk for pregnancy and could be subjected to monthly pregnancy testing when it is not medically necessary.

Consider the following patient scenario. A transgender man presents to your dermatology office seeking treatment of severe nodulocystic acne. He was placed on hormonal replacement therapy with exogenous testosterone—injections, oral pills, topical gel, topical patches, or subdermal pellets—to achieve secondary sex characteristics and promote gender congruence. The patient mentions he has been amenorrheic for several months now. He has tried many topical acne treatments as well as oral antibiotics without much benefit and is now interested in enrolling in iPLEDGE to obtain isotretinoin. With the prior iPLEDGE registration packets, how would this transgender man be classified? As a female with childbearing potential due to his retained ovaries and uterus? What if he did not endorse engaging in sexual intercourse that could result in pregnancy?

Transgender patients have unique and unmet needs that often are overlooked and prevent them from equitable, gender-affirming health care. For example, in a prospective study following 20 transgender men starting hormone replacement therapy, the percentage of patients with facial acne increased from 35% to 82% after 6 months of therapy.⁵ In addition, the increased psychosocial burden of acne may be especially difficult in these patients, as they already report higher rates of depression and suicidal ideation compared with their heterosexual cisgender peers.⁴ Further, the primary patient populations receiving isotretinoin typically are adolescents and young adults who are undergoing major physical, mental, and hormonal changes. Self-discovery and self-actualization develop over time, and our role as physicians is to advocate for all aspects of our patients’ health and eliminate barriers to optimal care.

Inclusive Language in iPLEDGE Categories

It is important to streamline access to care for all patients, and gender-affirming, culturally sensitive language is essential to building trust and understanding between patients and providers. Howa Yeung, MD, MSc, a dermatologist at Emory University (Atlanta, Georgia) who advocated for gender-neutral iPLEDGE registration, welcomes the change and stated it “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”³

Sanchez et al⁶ provided a list of structured questions providers can ask their patients to assess their risk regarding pregnancy: (1) Do you have a uterus and/or ovaries?, (2) Are you engaging in sexual intercourse with a person who has a penis?, and (3) If yes to these questions, what form(s) of birth control are you using? Providers should preface these questions with the following statement: “It is important that I ask these questions to assess your risk for becoming pregnant on this medication because isotretinoin can cause very serious birth defects.” It is important to review these questions and practice asking them so residents can operate from the same place of openness and understanding when caring for their patients.

Final Thoughts

The landscape of isotretinoin prescribing currently is changing on a day-to-day basis. As residents, it is important we stay up to date with the changes regarding our regularly dispensed medications. The main modification made to the iPLEDGE REMS system was switching the risk categories from 3 (females who can get pregnant, females who cannot get pregnant, males) to 2 (people who can get pregnant, people who cannot get pregnant). This change will make registration for iPLEDGE less complex and more inclusive for all patients. It is important for residents to stay at the forefront of these patient health issues and barriers to equal care, and this change represents a step in the right direction.

Isotretinoin is one of the most highly regulated dermatologic medications on the market. The main reason for regulation through the US Food and Drug Administration (FDA)–managed iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) is to minimize the drug’s teratogenic potential, as isotretinoin can cause profound birth defects. The program originally categorized patients into 1 of 3 categories: (1) females of reproductive potential, (2) females not of reproductive potential, and (3) males. Unless the patient commits to abstinence, the program required female patients of childbearing potential to be on 2 forms of birth control and undergo regular pregnancy testing before obtaining refills. Over the last few years, the American Academy of Dermatology Association (AADA) has been advocating for changes to the iPLEDGE system. Proposed changes have included decreasing attestation frequency for patients who cannot get pregnant, increasing contraception counseling and options, and changing enrollment guidelines to encompass all gender and sexual minorities. As of December 13, 2021, the iPLEDGE system changed enrollment categories to reflect the AADA’s wishes and rolled out gender-neutral categories for enrollment in iPLEDGE. This change will simplify and enhance patients’ experience when starting isotretinoin.

Developing Inclusive iPLEDGE Categories

In recent years, dermatologists and patients have viewed these strict gender-based categories as limiting and problematic, especially for their transgender patients and female patients of childbearing potential who exclusively engage in intercourse with cisgender females. The United States has more than 10 million LGBTQIA+ citizens and an estimated 1.4 million adults who identify as transgender individuals, rendering the previously established gender-binary iPLEDGE categories outdated.^1,2

As a result, over the last few years, dermatologists, LGBTQIA+ allies, and patients have urged the FDA to create a gender-neutral registration process for iPLEDGE. With support from the AADA, the new modifications were approved for implementation and include 2 risk categories: (1) people who can get pregnant and (2) people who cannot get pregnant.³

As exciting as these changes are for the future of dermatologic practice, the actual transition to the new iPLEDGE system was described as a “failure, chaotic, and a disaster” due to additional changes made at the same time.⁴ The iPLEDGE system was switched to a new website administered by a different vendor and required providers to confirm each patient online by December 13, 2021. In addition, the new system required pharmacists to obtain risk management authorization via the iPLEDGE REMS website or by calling the iPLEDGE REMS center before dispensing isotretinoin. This overhaul did not work as planned, as the new website was constantly down and it was nearly impossible to reach a contact over the telephone. The complications resulted in major disruptions and delayed prescriptions for thousands of patients nationwide as well as a great disruption in workflow for physicians and pharmacists. The AADA subsequently met with the Isotretinoin Products Manufacturers Group to create workable solutions for these issues.

On January 14, 2022, the FDA posted updates regarding access to the iPLEDGE system. They have worked with the Isotretinoin Products Manufacturers Group to create workable solutions for patients and physicians while transferring the patients’ information to the new database. Their solution includes allowing physicians to send patients login links through their email to access their account instead of waiting for the call center. The majority of iPLEDGE users now have access to their accounts without issues, and the gender-neutral guidelines have been in place since the original change.

Impact of iPLEDGE Categories on Transgender Patients

These changes specifically will improve the experience of transgender men and cisgender women who are at no risk for pregnancy and could be subjected to monthly pregnancy testing when it is not medically necessary.

Consider the following patient scenario. A transgender man presents to your dermatology office seeking treatment of severe nodulocystic acne. He was placed on hormonal replacement therapy with exogenous testosterone—injections, oral pills, topical gel, topical patches, or subdermal pellets—to achieve secondary sex characteristics and promote gender congruence. The patient mentions he has been amenorrheic for several months now. He has tried many topical acne treatments as well as oral antibiotics without much benefit and is now interested in enrolling in iPLEDGE to obtain isotretinoin. With the prior iPLEDGE registration packets, how would this transgender man be classified? As a female with childbearing potential due to his retained ovaries and uterus? What if he did not endorse engaging in sexual intercourse that could result in pregnancy?

Transgender patients have unique and unmet needs that often are overlooked and prevent them from equitable, gender-affirming health care. For example, in a prospective study following 20 transgender men starting hormone replacement therapy, the percentage of patients with facial acne increased from 35% to 82% after 6 months of therapy.⁵ In addition, the increased psychosocial burden of acne may be especially difficult in these patients, as they already report higher rates of depression and suicidal ideation compared with their heterosexual cisgender peers.⁴ Further, the primary patient populations receiving isotretinoin typically are adolescents and young adults who are undergoing major physical, mental, and hormonal changes. Self-discovery and self-actualization develop over time, and our role as physicians is to advocate for all aspects of our patients’ health and eliminate barriers to optimal care.

Inclusive Language in iPLEDGE Categories

It is important to streamline access to care for all patients, and gender-affirming, culturally sensitive language is essential to building trust and understanding between patients and providers. Howa Yeung, MD, MSc, a dermatologist at Emory University (Atlanta, Georgia) who advocated for gender-neutral iPLEDGE registration, welcomes the change and stated it “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”³

Sanchez et al⁶ provided a list of structured questions providers can ask their patients to assess their risk regarding pregnancy: (1) Do you have a uterus and/or ovaries?, (2) Are you engaging in sexual intercourse with a person who has a penis?, and (3) If yes to these questions, what form(s) of birth control are you using? Providers should preface these questions with the following statement: “It is important that I ask these questions to assess your risk for becoming pregnant on this medication because isotretinoin can cause very serious birth defects.” It is important to review these questions and practice asking them so residents can operate from the same place of openness and understanding when caring for their patients.

Final Thoughts

The landscape of isotretinoin prescribing currently is changing on a day-to-day basis. As residents, it is important we stay up to date with the changes regarding our regularly dispensed medications. The main modification made to the iPLEDGE REMS system was switching the risk categories from 3 (females who can get pregnant, females who cannot get pregnant, males) to 2 (people who can get pregnant, people who cannot get pregnant). This change will make registration for iPLEDGE less complex and more inclusive for all patients. It is important for residents to stay at the forefront of these patient health issues and barriers to equal care, and this change represents a step in the right direction.

Isotretinoin is one of the most highly regulated dermatologic medications on the market. The main reason for regulation through the US Food and Drug Administration (FDA)–managed iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) is to minimize the drug’s teratogenic potential, as isotretinoin can cause profound birth defects. The program originally categorized patients into 1 of 3 categories: (1) females of reproductive potential, (2) females not of reproductive potential, and (3) males. Unless the patient commits to abstinence, the program required female patients of childbearing potential to be on 2 forms of birth control and undergo regular pregnancy testing before obtaining refills. Over the last few years, the American Academy of Dermatology Association (AADA) has been advocating for changes to the iPLEDGE system. Proposed changes have included decreasing attestation frequency for patients who cannot get pregnant, increasing contraception counseling and options, and changing enrollment guidelines to encompass all gender and sexual minorities. As of December 13, 2021, the iPLEDGE system changed enrollment categories to reflect the AADA’s wishes and rolled out gender-neutral categories for enrollment in iPLEDGE. This change will simplify and enhance patients’ experience when starting isotretinoin.

Developing Inclusive iPLEDGE Categories

In recent years, dermatologists and patients have viewed these strict gender-based categories as limiting and problematic, especially for their transgender patients and female patients of childbearing potential who exclusively engage in intercourse with cisgender females. The United States has more than 10 million LGBTQIA+ citizens and an estimated 1.4 million adults who identify as transgender individuals, rendering the previously established gender-binary iPLEDGE categories outdated.^1,2

As a result, over the last few years, dermatologists, LGBTQIA+ allies, and patients have urged the FDA to create a gender-neutral registration process for iPLEDGE. With support from the AADA, the new modifications were approved for implementation and include 2 risk categories: (1) people who can get pregnant and (2) people who cannot get pregnant.³

As exciting as these changes are for the future of dermatologic practice, the actual transition to the new iPLEDGE system was described as a “failure, chaotic, and a disaster” due to additional changes made at the same time.⁴ The iPLEDGE system was switched to a new website administered by a different vendor and required providers to confirm each patient online by December 13, 2021. In addition, the new system required pharmacists to obtain risk management authorization via the iPLEDGE REMS website or by calling the iPLEDGE REMS center before dispensing isotretinoin. This overhaul did not work as planned, as the new website was constantly down and it was nearly impossible to reach a contact over the telephone. The complications resulted in major disruptions and delayed prescriptions for thousands of patients nationwide as well as a great disruption in workflow for physicians and pharmacists. The AADA subsequently met with the Isotretinoin Products Manufacturers Group to create workable solutions for these issues.

On January 14, 2022, the FDA posted updates regarding access to the iPLEDGE system. They have worked with the Isotretinoin Products Manufacturers Group to create workable solutions for patients and physicians while transferring the patients’ information to the new database. Their solution includes allowing physicians to send patients login links through their email to access their account instead of waiting for the call center. The majority of iPLEDGE users now have access to their accounts without issues, and the gender-neutral guidelines have been in place since the original change.

Impact of iPLEDGE Categories on Transgender Patients

These changes specifically will improve the experience of transgender men and cisgender women who are at no risk for pregnancy and could be subjected to monthly pregnancy testing when it is not medically necessary.

Consider the following patient scenario. A transgender man presents to your dermatology office seeking treatment of severe nodulocystic acne. He was placed on hormonal replacement therapy with exogenous testosterone—injections, oral pills, topical gel, topical patches, or subdermal pellets—to achieve secondary sex characteristics and promote gender congruence. The patient mentions he has been amenorrheic for several months now. He has tried many topical acne treatments as well as oral antibiotics without much benefit and is now interested in enrolling in iPLEDGE to obtain isotretinoin. With the prior iPLEDGE registration packets, how would this transgender man be classified? As a female with childbearing potential due to his retained ovaries and uterus? What if he did not endorse engaging in sexual intercourse that could result in pregnancy?

Transgender patients have unique and unmet needs that often are overlooked and prevent them from equitable, gender-affirming health care. For example, in a prospective study following 20 transgender men starting hormone replacement therapy, the percentage of patients with facial acne increased from 35% to 82% after 6 months of therapy.⁵ In addition, the increased psychosocial burden of acne may be especially difficult in these patients, as they already report higher rates of depression and suicidal ideation compared with their heterosexual cisgender peers.⁴ Further, the primary patient populations receiving isotretinoin typically are adolescents and young adults who are undergoing major physical, mental, and hormonal changes. Self-discovery and self-actualization develop over time, and our role as physicians is to advocate for all aspects of our patients’ health and eliminate barriers to optimal care.

Inclusive Language in iPLEDGE Categories

It is important to streamline access to care for all patients, and gender-affirming, culturally sensitive language is essential to building trust and understanding between patients and providers. Howa Yeung, MD, MSc, a dermatologist at Emory University (Atlanta, Georgia) who advocated for gender-neutral iPLEDGE registration, welcomes the change and stated it “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”³

Sanchez et al⁶ provided a list of structured questions providers can ask their patients to assess their risk regarding pregnancy: (1) Do you have a uterus and/or ovaries?, (2) Are you engaging in sexual intercourse with a person who has a penis?, and (3) If yes to these questions, what form(s) of birth control are you using? Providers should preface these questions with the following statement: “It is important that I ask these questions to assess your risk for becoming pregnant on this medication because isotretinoin can cause very serious birth defects.” It is important to review these questions and practice asking them so residents can operate from the same place of openness and understanding when caring for their patients.

Final Thoughts

The landscape of isotretinoin prescribing currently is changing on a day-to-day basis. As residents, it is important we stay up to date with the changes regarding our regularly dispensed medications. The main modification made to the iPLEDGE REMS system was switching the risk categories from 3 (females who can get pregnant, females who cannot get pregnant, males) to 2 (people who can get pregnant, people who cannot get pregnant). This change will make registration for iPLEDGE less complex and more inclusive for all patients. It is important for residents to stay at the forefront of these patient health issues and barriers to equal care, and this change represents a step in the right direction.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.