Too much or too little sleep, daytime naps, and other sleep patterns may increase the risk of developing esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), suggest researchers at Washington University, St. Louis.

In their prospective study, the team found that individuals who slept more than 9 hours a night had double the risk of getting EAC after 2 or more years (hazard ratio, 2.06) compared with a person sleeping a “standard” 7 hours a night.

Conversely, people who slept fewer than 6 hours were 21% more likely to be diagnosed with EAC and 63% more likely to get ESCC after 2 years.

The research team, led by Yin Cao, ScD, associate professor of surgery, mined UK Biobank data between 2006 and 2016 for the sleep habits of 393,114 people, then followed them for up to 10 years to see how many developed esophageal cancer. During this time, 294 people developed EAC, and 95 were diagnosed with ESCC.

The study was published in Cancer, Epidemiology Biomarkers and Prevention.

Dr. Cao said that she and her team decided to conduct the study because they were intrigued by evidence suggesting a link between shorter sleep duration with ESCC and Barrett esophagus, the precursor of EAC. “Yet other sleep behaviours [had] not been comprehensively evaluated,” Dr. Cao said.

The team also assessed daytime sleep behavior. They found that taking daytime naps or experiencing sleepiness did not bode well down the road with regard to esophageal cancer, depending on the type of cancer. Individuals who “sometimes” took daytime naps were at 39% increased risk of EAC, and those who “usually” experienced sleepiness during the day had twice the risk of ESCC after 2 years.

Chronotype, a person’s natural rhythm of daytime sleepiness, also appeared to play a role. For example, being an “evening person” increased the risk of EAC by 32% and almost tripled the risk of ESCC compared to being a “morning person.”

Neither snoring nor insomnia affected the risk of either type of esophageal cancer.

Dr. Cao was surprised that both short and long sleep duration, napping, and daytime sleepiness turned out to be risk factors for esophageal cancer.

The mechanisms underlying these associations are “likely complex,” she said, adding that different aspects of sleep behavior might be driving cancer through differing routes.

“Disruption of circadian physiology could result in gastroesophageal reflux disease (GERD), the most important risk factor for EAC, via altering the expression of circadian-clock genes in esophagus tissue or reducing the expression of melatonin,” said Dr. Cao. “Both excess sleep and sleep deprivation might relate to immune dysfunction, which might lead to an increased susceptibility to esophageal cancer.”

In an interview, when asked whether other, simpler explanations were possible, Dr. Cao acknowledged that other associations were a potential source of confusion. For example, obesity is known to affect both quality of sleep and cancer risk. Dr. Cao said in their analyses, the team adjusted for a myriad of likely confounders, such as sex, smoking status, and shift-work status, in addition to body mass index and the Townsend Deprivation Index, a poverty measure.

Another factor that could have muddied the results was reverse causation, the possibility that already-present esophageal cancer was causing fatigue and poor sleep patterns instead of the other way around. For this reason, Dr. Cao’s team conducted a separate analysis that excluded patients who were diagnosed with esophageal cancer during the first 2 years of follow-up. (Data from this separate analysis, available in the supplementary tables, were used for the current article.)

Dr. Cao concluded that her team’s data “may serve as modifying risk factors for esophageal adenoma carcinoma” but that “additional validation and mechanistic studies are needed.”

The study was supported by a National Institutes of Health grant. Dr. Cao has received personal fees from Geneoscopy outside the published work.

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

Too much or too little sleep, daytime naps, and other sleep patterns may increase the risk of developing esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), suggest researchers at Washington University, St. Louis.

In their prospective study, the team found that individuals who slept more than 9 hours a night had double the risk of getting EAC after 2 or more years (hazard ratio, 2.06) compared with a person sleeping a “standard” 7 hours a night.

Conversely, people who slept fewer than 6 hours were 21% more likely to be diagnosed with EAC and 63% more likely to get ESCC after 2 years.

The research team, led by Yin Cao, ScD, associate professor of surgery, mined UK Biobank data between 2006 and 2016 for the sleep habits of 393,114 people, then followed them for up to 10 years to see how many developed esophageal cancer. During this time, 294 people developed EAC, and 95 were diagnosed with ESCC.

The study was published in Cancer, Epidemiology Biomarkers and Prevention.

Dr. Cao said that she and her team decided to conduct the study because they were intrigued by evidence suggesting a link between shorter sleep duration with ESCC and Barrett esophagus, the precursor of EAC. “Yet other sleep behaviours [had] not been comprehensively evaluated,” Dr. Cao said.

The team also assessed daytime sleep behavior. They found that taking daytime naps or experiencing sleepiness did not bode well down the road with regard to esophageal cancer, depending on the type of cancer. Individuals who “sometimes” took daytime naps were at 39% increased risk of EAC, and those who “usually” experienced sleepiness during the day had twice the risk of ESCC after 2 years.

Chronotype, a person’s natural rhythm of daytime sleepiness, also appeared to play a role. For example, being an “evening person” increased the risk of EAC by 32% and almost tripled the risk of ESCC compared to being a “morning person.”

Neither snoring nor insomnia affected the risk of either type of esophageal cancer.

Dr. Cao was surprised that both short and long sleep duration, napping, and daytime sleepiness turned out to be risk factors for esophageal cancer.

The mechanisms underlying these associations are “likely complex,” she said, adding that different aspects of sleep behavior might be driving cancer through differing routes.

“Disruption of circadian physiology could result in gastroesophageal reflux disease (GERD), the most important risk factor for EAC, via altering the expression of circadian-clock genes in esophagus tissue or reducing the expression of melatonin,” said Dr. Cao. “Both excess sleep and sleep deprivation might relate to immune dysfunction, which might lead to an increased susceptibility to esophageal cancer.”

In an interview, when asked whether other, simpler explanations were possible, Dr. Cao acknowledged that other associations were a potential source of confusion. For example, obesity is known to affect both quality of sleep and cancer risk. Dr. Cao said in their analyses, the team adjusted for a myriad of likely confounders, such as sex, smoking status, and shift-work status, in addition to body mass index and the Townsend Deprivation Index, a poverty measure.

Another factor that could have muddied the results was reverse causation, the possibility that already-present esophageal cancer was causing fatigue and poor sleep patterns instead of the other way around. For this reason, Dr. Cao’s team conducted a separate analysis that excluded patients who were diagnosed with esophageal cancer during the first 2 years of follow-up. (Data from this separate analysis, available in the supplementary tables, were used for the current article.)

Dr. Cao concluded that her team’s data “may serve as modifying risk factors for esophageal adenoma carcinoma” but that “additional validation and mechanistic studies are needed.”

The study was supported by a National Institutes of Health grant. Dr. Cao has received personal fees from Geneoscopy outside the published work.

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

Too much or too little sleep, daytime naps, and other sleep patterns may increase the risk of developing esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), suggest researchers at Washington University, St. Louis.

In their prospective study, the team found that individuals who slept more than 9 hours a night had double the risk of getting EAC after 2 or more years (hazard ratio, 2.06) compared with a person sleeping a “standard” 7 hours a night.

Conversely, people who slept fewer than 6 hours were 21% more likely to be diagnosed with EAC and 63% more likely to get ESCC after 2 years.

The research team, led by Yin Cao, ScD, associate professor of surgery, mined UK Biobank data between 2006 and 2016 for the sleep habits of 393,114 people, then followed them for up to 10 years to see how many developed esophageal cancer. During this time, 294 people developed EAC, and 95 were diagnosed with ESCC.

The study was published in Cancer, Epidemiology Biomarkers and Prevention.

Dr. Cao said that she and her team decided to conduct the study because they were intrigued by evidence suggesting a link between shorter sleep duration with ESCC and Barrett esophagus, the precursor of EAC. “Yet other sleep behaviours [had] not been comprehensively evaluated,” Dr. Cao said.

The team also assessed daytime sleep behavior. They found that taking daytime naps or experiencing sleepiness did not bode well down the road with regard to esophageal cancer, depending on the type of cancer. Individuals who “sometimes” took daytime naps were at 39% increased risk of EAC, and those who “usually” experienced sleepiness during the day had twice the risk of ESCC after 2 years.

Chronotype, a person’s natural rhythm of daytime sleepiness, also appeared to play a role. For example, being an “evening person” increased the risk of EAC by 32% and almost tripled the risk of ESCC compared to being a “morning person.”

Neither snoring nor insomnia affected the risk of either type of esophageal cancer.

Dr. Cao was surprised that both short and long sleep duration, napping, and daytime sleepiness turned out to be risk factors for esophageal cancer.

The mechanisms underlying these associations are “likely complex,” she said, adding that different aspects of sleep behavior might be driving cancer through differing routes.

“Disruption of circadian physiology could result in gastroesophageal reflux disease (GERD), the most important risk factor for EAC, via altering the expression of circadian-clock genes in esophagus tissue or reducing the expression of melatonin,” said Dr. Cao. “Both excess sleep and sleep deprivation might relate to immune dysfunction, which might lead to an increased susceptibility to esophageal cancer.”

In an interview, when asked whether other, simpler explanations were possible, Dr. Cao acknowledged that other associations were a potential source of confusion. For example, obesity is known to affect both quality of sleep and cancer risk. Dr. Cao said in their analyses, the team adjusted for a myriad of likely confounders, such as sex, smoking status, and shift-work status, in addition to body mass index and the Townsend Deprivation Index, a poverty measure.

Another factor that could have muddied the results was reverse causation, the possibility that already-present esophageal cancer was causing fatigue and poor sleep patterns instead of the other way around. For this reason, Dr. Cao’s team conducted a separate analysis that excluded patients who were diagnosed with esophageal cancer during the first 2 years of follow-up. (Data from this separate analysis, available in the supplementary tables, were used for the current article.)

Dr. Cao concluded that her team’s data “may serve as modifying risk factors for esophageal adenoma carcinoma” but that “additional validation and mechanistic studies are needed.”

The study was supported by a National Institutes of Health grant. Dr. Cao has received personal fees from Geneoscopy outside the published work.

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

Dermatologic disparities disproportionately affect patients with skin of color (SOC). Two studies assessing the diagnostic accuracy of medical students have shown disparities in diagnosing common skin conditions presenting in darker skin compared to lighter skin at early stages of training.^1,2 This knowledge gap could be attributed to the underrepresentation of SOC in dermatologic textbooks, journals, and educational curricula.^3-6 It is important for dermatologists as well as physicians in other specialties and ancillary health care workers involved in treating or triaging dermatologic diseases to recognize common skin conditions presenting in SOC. We sought to evaluate the effectiveness of a focused educational module for improving diagnostic accuracy and confidence in treating SOC among interprofessional health care providers.

Methods

Interprofessional health care providers—medical students, residents/fellows, attending physicians, advanced practice providers (APPs), and nurses practicing across various medical specialties—at The University of Texas at Austin Dell Medical School and Ascension Medical Group (both in Austin, Texas) were invited to participate in an institutional review board–exempt study involving a virtual SOC educational module from February through May 2021. The 1-hour module involved a pretest, a 15-minute lecture, an immediate posttest, and a 3-month posttest. All tests included the same 40 multiple-choice questions of 20 dermatologic conditions portrayed in lighter and darker skin types from VisualDx.com, and participants were asked to identify the condition in each photograph. Questions appeared one at a time in a randomized order, and answers could not be changed once submitted.

For analysis, the dermatologic conditions were categorized into 4 groups: cancerous, infectious, inflammatory, and SOC-associated conditions. Cancerous conditions included basal cell carcinoma, squamous cell carcinoma, and melanoma. Infectious conditions included herpes zoster, tinea corporis, tinea versicolor, staphylococcal scalded skin syndrome, and verruca vulgaris. Inflammatory conditions included acne, atopic dermatitis, pityriasis rosea, psoriasis, seborrheic dermatitis, contact dermatitis, lichen planus, and urticaria. Skin of color–associated conditions included hidradenitis suppurativa, acanthosis nigricans, keloid, and melasma. Two questions utilizing a 5-point Likert scale assessing confidence in diagnosing light and dark skin also were included.

The pre-recorded 15-minute video lecture was given by 2 dermatology residents (P.L.K. and C.P.), and the learning objectives covered morphologic differences in lighter skin and darker skin, comparisons of common dermatologic diseases in lighter skin and darker skin, diseases more commonly affecting patients with SOC, and treatment considerations for conditions affecting skin and hair in patients with SOC. Photographs from the diagnostic accuracy assessment were not reused in the lecture. Detailed explanations on morphology, diagnostic pearls, and treatment options for all conditions tested were provided to participants upon completion of the 3-month posttest.

Statistical Analysis—Test scores were compared between conditions shown in lighter and darker skin types and from the pretest to the immediate posttest and 3-month posttest. Multiple linear regression was used to assess for intervention effects on lighter and darker skin scores controlling for provider type and specialty. All tests were 2-sided with significance at P<.05. Analyses were conducted using Stata 17.

Results

One hundred participants completed the pretest and immediate posttest, 36 of whom also completed the 3-month posttest (Table). There was no significant difference in baseline characteristics between the pretest and 3-month posttest groups.

Test scores were correlated with provider type and specialty but not age, sex, or race/ethnicity. Specializing in dermatology and being a resident or attending physician were independently associated with higher test scores. Mean pretest diagnostic accuracy and confidence scores were higher for skin conditions shown in lighter skin compared with those shown in darker skin (13.6 vs 11.3 and 2.7 vs 1.9, respectively; both P<.001). Pretest diagnostic accuracy was significantly higher for skin conditions shown in lighter skin compared with darker skin for cancerous, inflammatory, and infectious conditions (72% vs 50%, 68% vs 55%, and 57% vs 47%, respectively; P<.001 for all)(Figure 1). Skin of color–associated conditions were not associated with significantly different scores for lighter skin compared with darker skin (79% vs 75%; P=.059).

Controlling for provider type and specialty, significantly improved diagnostic accuracy was seen in immediate posttest scores compared with pretest scores for conditions shown in both lighter and darker skin types (lighter: 15.2 vs 13.6; darker: 13.3 vs 11.3; both P<.001)(Figure 2). The immediate posttest demonstrated higher mean diagnostic accuracy and confidence scores for skin conditions shown in lighter skin compared with darker skin (diagnostic accuracy: 15.2 vs 13.3; confidence: 3.0 vs 2.6; both P<.001), but the disparity between scores was less than in the pretest.

Following the 3-month posttest, improvement in diagnostic accuracy was noted among both lighter and darker skin types compared with the pretest, but the difference remained significant only for conditions shown in darker skin (mean scores, 11.3 vs 13.3; P<.01). Similarly, confidence in diagnosing conditions in both lighter and darker skin improved following the immediate posttest (mean scores, 2.7 vs 3.0 and 1.9 vs 2.6; both P<.001), and this improvement remained significant for only darker skin following the 3-month posttest (mean scores, 1.9 vs 2.3; P<.001). Despite these improvements, diagnostic accuracy and confidence remained higher for skin conditions shown in lighter skin compared with darker skin (diagnostic accuracy: 14.7 vs 13.3; P<.01; confidence: 2.8 vs 2.3; P<.001), though the disparity between scores was again less than in the pretest.

Comment

Our study showed that there are diagnostic disparities between lighter and darker skin types among interprofessional health care providers. Education on SOC should extend to interprofessional health care providers and other medical specialties involved in treating or triaging dermatologic diseases. A focused educational module may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in SOC. Differences in diagnostic accuracy between conditions shown in lighter and darker skin types were noted for the disease categories of infectious, cancerous, and inflammatory conditions, with the exception of conditions more frequently seen in patients with SOC. Learning resources for SOC-associated conditions are more likely to have greater representation of images depicting darker skin types.⁷ Future educational interventions may need to focus on dermatologic conditions that are not preferentially seen in patients with SOC. In our study, the pretest scores for conditions shown in darker skin were lowest among infectious and cancerous conditions. For infections, certain morphologic clues such as erythema are important for diagnosis but may be more subtle or difficult to discern in darker skin. It also is possible that providers may be less likely to suspect skin cancer in patients with SOC given that the morphologic presentation and/or anatomic site of involvement for skin cancers in SOC differs from those in lighter skin. Future educational interventions targeting disparities in diagnostic accuracy should focus on conditions that are not specifically associated with SOC.

Limitations of our study included the small number of participants, the study population came from a single institution, and a possible selection bias for providers interested in dermatology.

Conclusion

Disparities exist among interprofessional health care providers when treating conditions in patients with lighter skin compared to darker skin. An educational module for health care providers may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in patients with SOC.

Dermatologic disparities disproportionately affect patients with skin of color (SOC). Two studies assessing the diagnostic accuracy of medical students have shown disparities in diagnosing common skin conditions presenting in darker skin compared to lighter skin at early stages of training.^1,2 This knowledge gap could be attributed to the underrepresentation of SOC in dermatologic textbooks, journals, and educational curricula.^3-6 It is important for dermatologists as well as physicians in other specialties and ancillary health care workers involved in treating or triaging dermatologic diseases to recognize common skin conditions presenting in SOC. We sought to evaluate the effectiveness of a focused educational module for improving diagnostic accuracy and confidence in treating SOC among interprofessional health care providers.

Methods

Interprofessional health care providers—medical students, residents/fellows, attending physicians, advanced practice providers (APPs), and nurses practicing across various medical specialties—at The University of Texas at Austin Dell Medical School and Ascension Medical Group (both in Austin, Texas) were invited to participate in an institutional review board–exempt study involving a virtual SOC educational module from February through May 2021. The 1-hour module involved a pretest, a 15-minute lecture, an immediate posttest, and a 3-month posttest. All tests included the same 40 multiple-choice questions of 20 dermatologic conditions portrayed in lighter and darker skin types from VisualDx.com, and participants were asked to identify the condition in each photograph. Questions appeared one at a time in a randomized order, and answers could not be changed once submitted.

For analysis, the dermatologic conditions were categorized into 4 groups: cancerous, infectious, inflammatory, and SOC-associated conditions. Cancerous conditions included basal cell carcinoma, squamous cell carcinoma, and melanoma. Infectious conditions included herpes zoster, tinea corporis, tinea versicolor, staphylococcal scalded skin syndrome, and verruca vulgaris. Inflammatory conditions included acne, atopic dermatitis, pityriasis rosea, psoriasis, seborrheic dermatitis, contact dermatitis, lichen planus, and urticaria. Skin of color–associated conditions included hidradenitis suppurativa, acanthosis nigricans, keloid, and melasma. Two questions utilizing a 5-point Likert scale assessing confidence in diagnosing light and dark skin also were included.

The pre-recorded 15-minute video lecture was given by 2 dermatology residents (P.L.K. and C.P.), and the learning objectives covered morphologic differences in lighter skin and darker skin, comparisons of common dermatologic diseases in lighter skin and darker skin, diseases more commonly affecting patients with SOC, and treatment considerations for conditions affecting skin and hair in patients with SOC. Photographs from the diagnostic accuracy assessment were not reused in the lecture. Detailed explanations on morphology, diagnostic pearls, and treatment options for all conditions tested were provided to participants upon completion of the 3-month posttest.

Statistical Analysis—Test scores were compared between conditions shown in lighter and darker skin types and from the pretest to the immediate posttest and 3-month posttest. Multiple linear regression was used to assess for intervention effects on lighter and darker skin scores controlling for provider type and specialty. All tests were 2-sided with significance at P<.05. Analyses were conducted using Stata 17.

Results

One hundred participants completed the pretest and immediate posttest, 36 of whom also completed the 3-month posttest (Table). There was no significant difference in baseline characteristics between the pretest and 3-month posttest groups.

Test scores were correlated with provider type and specialty but not age, sex, or race/ethnicity. Specializing in dermatology and being a resident or attending physician were independently associated with higher test scores. Mean pretest diagnostic accuracy and confidence scores were higher for skin conditions shown in lighter skin compared with those shown in darker skin (13.6 vs 11.3 and 2.7 vs 1.9, respectively; both P<.001). Pretest diagnostic accuracy was significantly higher for skin conditions shown in lighter skin compared with darker skin for cancerous, inflammatory, and infectious conditions (72% vs 50%, 68% vs 55%, and 57% vs 47%, respectively; P<.001 for all)(Figure 1). Skin of color–associated conditions were not associated with significantly different scores for lighter skin compared with darker skin (79% vs 75%; P=.059).

Controlling for provider type and specialty, significantly improved diagnostic accuracy was seen in immediate posttest scores compared with pretest scores for conditions shown in both lighter and darker skin types (lighter: 15.2 vs 13.6; darker: 13.3 vs 11.3; both P<.001)(Figure 2). The immediate posttest demonstrated higher mean diagnostic accuracy and confidence scores for skin conditions shown in lighter skin compared with darker skin (diagnostic accuracy: 15.2 vs 13.3; confidence: 3.0 vs 2.6; both P<.001), but the disparity between scores was less than in the pretest.

Following the 3-month posttest, improvement in diagnostic accuracy was noted among both lighter and darker skin types compared with the pretest, but the difference remained significant only for conditions shown in darker skin (mean scores, 11.3 vs 13.3; P<.01). Similarly, confidence in diagnosing conditions in both lighter and darker skin improved following the immediate posttest (mean scores, 2.7 vs 3.0 and 1.9 vs 2.6; both P<.001), and this improvement remained significant for only darker skin following the 3-month posttest (mean scores, 1.9 vs 2.3; P<.001). Despite these improvements, diagnostic accuracy and confidence remained higher for skin conditions shown in lighter skin compared with darker skin (diagnostic accuracy: 14.7 vs 13.3; P<.01; confidence: 2.8 vs 2.3; P<.001), though the disparity between scores was again less than in the pretest.

Comment

Our study showed that there are diagnostic disparities between lighter and darker skin types among interprofessional health care providers. Education on SOC should extend to interprofessional health care providers and other medical specialties involved in treating or triaging dermatologic diseases. A focused educational module may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in SOC. Differences in diagnostic accuracy between conditions shown in lighter and darker skin types were noted for the disease categories of infectious, cancerous, and inflammatory conditions, with the exception of conditions more frequently seen in patients with SOC. Learning resources for SOC-associated conditions are more likely to have greater representation of images depicting darker skin types.⁷ Future educational interventions may need to focus on dermatologic conditions that are not preferentially seen in patients with SOC. In our study, the pretest scores for conditions shown in darker skin were lowest among infectious and cancerous conditions. For infections, certain morphologic clues such as erythema are important for diagnosis but may be more subtle or difficult to discern in darker skin. It also is possible that providers may be less likely to suspect skin cancer in patients with SOC given that the morphologic presentation and/or anatomic site of involvement for skin cancers in SOC differs from those in lighter skin. Future educational interventions targeting disparities in diagnostic accuracy should focus on conditions that are not specifically associated with SOC.

Limitations of our study included the small number of participants, the study population came from a single institution, and a possible selection bias for providers interested in dermatology.

Conclusion

Disparities exist among interprofessional health care providers when treating conditions in patients with lighter skin compared to darker skin. An educational module for health care providers may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in patients with SOC.

Dermatologic disparities disproportionately affect patients with skin of color (SOC). Two studies assessing the diagnostic accuracy of medical students have shown disparities in diagnosing common skin conditions presenting in darker skin compared to lighter skin at early stages of training.^1,2 This knowledge gap could be attributed to the underrepresentation of SOC in dermatologic textbooks, journals, and educational curricula.^3-6 It is important for dermatologists as well as physicians in other specialties and ancillary health care workers involved in treating or triaging dermatologic diseases to recognize common skin conditions presenting in SOC. We sought to evaluate the effectiveness of a focused educational module for improving diagnostic accuracy and confidence in treating SOC among interprofessional health care providers.

Methods

Interprofessional health care providers—medical students, residents/fellows, attending physicians, advanced practice providers (APPs), and nurses practicing across various medical specialties—at The University of Texas at Austin Dell Medical School and Ascension Medical Group (both in Austin, Texas) were invited to participate in an institutional review board–exempt study involving a virtual SOC educational module from February through May 2021. The 1-hour module involved a pretest, a 15-minute lecture, an immediate posttest, and a 3-month posttest. All tests included the same 40 multiple-choice questions of 20 dermatologic conditions portrayed in lighter and darker skin types from VisualDx.com, and participants were asked to identify the condition in each photograph. Questions appeared one at a time in a randomized order, and answers could not be changed once submitted.

For analysis, the dermatologic conditions were categorized into 4 groups: cancerous, infectious, inflammatory, and SOC-associated conditions. Cancerous conditions included basal cell carcinoma, squamous cell carcinoma, and melanoma. Infectious conditions included herpes zoster, tinea corporis, tinea versicolor, staphylococcal scalded skin syndrome, and verruca vulgaris. Inflammatory conditions included acne, atopic dermatitis, pityriasis rosea, psoriasis, seborrheic dermatitis, contact dermatitis, lichen planus, and urticaria. Skin of color–associated conditions included hidradenitis suppurativa, acanthosis nigricans, keloid, and melasma. Two questions utilizing a 5-point Likert scale assessing confidence in diagnosing light and dark skin also were included.

The pre-recorded 15-minute video lecture was given by 2 dermatology residents (P.L.K. and C.P.), and the learning objectives covered morphologic differences in lighter skin and darker skin, comparisons of common dermatologic diseases in lighter skin and darker skin, diseases more commonly affecting patients with SOC, and treatment considerations for conditions affecting skin and hair in patients with SOC. Photographs from the diagnostic accuracy assessment were not reused in the lecture. Detailed explanations on morphology, diagnostic pearls, and treatment options for all conditions tested were provided to participants upon completion of the 3-month posttest.

Statistical Analysis—Test scores were compared between conditions shown in lighter and darker skin types and from the pretest to the immediate posttest and 3-month posttest. Multiple linear regression was used to assess for intervention effects on lighter and darker skin scores controlling for provider type and specialty. All tests were 2-sided with significance at P<.05. Analyses were conducted using Stata 17.

Results

One hundred participants completed the pretest and immediate posttest, 36 of whom also completed the 3-month posttest (Table). There was no significant difference in baseline characteristics between the pretest and 3-month posttest groups.

Test scores were correlated with provider type and specialty but not age, sex, or race/ethnicity. Specializing in dermatology and being a resident or attending physician were independently associated with higher test scores. Mean pretest diagnostic accuracy and confidence scores were higher for skin conditions shown in lighter skin compared with those shown in darker skin (13.6 vs 11.3 and 2.7 vs 1.9, respectively; both P<.001). Pretest diagnostic accuracy was significantly higher for skin conditions shown in lighter skin compared with darker skin for cancerous, inflammatory, and infectious conditions (72% vs 50%, 68% vs 55%, and 57% vs 47%, respectively; P<.001 for all)(Figure 1). Skin of color–associated conditions were not associated with significantly different scores for lighter skin compared with darker skin (79% vs 75%; P=.059).

Controlling for provider type and specialty, significantly improved diagnostic accuracy was seen in immediate posttest scores compared with pretest scores for conditions shown in both lighter and darker skin types (lighter: 15.2 vs 13.6; darker: 13.3 vs 11.3; both P<.001)(Figure 2). The immediate posttest demonstrated higher mean diagnostic accuracy and confidence scores for skin conditions shown in lighter skin compared with darker skin (diagnostic accuracy: 15.2 vs 13.3; confidence: 3.0 vs 2.6; both P<.001), but the disparity between scores was less than in the pretest.

Following the 3-month posttest, improvement in diagnostic accuracy was noted among both lighter and darker skin types compared with the pretest, but the difference remained significant only for conditions shown in darker skin (mean scores, 11.3 vs 13.3; P<.01). Similarly, confidence in diagnosing conditions in both lighter and darker skin improved following the immediate posttest (mean scores, 2.7 vs 3.0 and 1.9 vs 2.6; both P<.001), and this improvement remained significant for only darker skin following the 3-month posttest (mean scores, 1.9 vs 2.3; P<.001). Despite these improvements, diagnostic accuracy and confidence remained higher for skin conditions shown in lighter skin compared with darker skin (diagnostic accuracy: 14.7 vs 13.3; P<.01; confidence: 2.8 vs 2.3; P<.001), though the disparity between scores was again less than in the pretest.

Comment

Our study showed that there are diagnostic disparities between lighter and darker skin types among interprofessional health care providers. Education on SOC should extend to interprofessional health care providers and other medical specialties involved in treating or triaging dermatologic diseases. A focused educational module may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in SOC. Differences in diagnostic accuracy between conditions shown in lighter and darker skin types were noted for the disease categories of infectious, cancerous, and inflammatory conditions, with the exception of conditions more frequently seen in patients with SOC. Learning resources for SOC-associated conditions are more likely to have greater representation of images depicting darker skin types.⁷ Future educational interventions may need to focus on dermatologic conditions that are not preferentially seen in patients with SOC. In our study, the pretest scores for conditions shown in darker skin were lowest among infectious and cancerous conditions. For infections, certain morphologic clues such as erythema are important for diagnosis but may be more subtle or difficult to discern in darker skin. It also is possible that providers may be less likely to suspect skin cancer in patients with SOC given that the morphologic presentation and/or anatomic site of involvement for skin cancers in SOC differs from those in lighter skin. Future educational interventions targeting disparities in diagnostic accuracy should focus on conditions that are not specifically associated with SOC.

Limitations of our study included the small number of participants, the study population came from a single institution, and a possible selection bias for providers interested in dermatology.

Conclusion

Disparities exist among interprofessional health care providers when treating conditions in patients with lighter skin compared to darker skin. An educational module for health care providers may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in patients with SOC.

Purpose of Medical Standards in the US Military

Young adults in the United States traditionally have viewed military service as a viable career given its stable salary, career training, opportunities for progression, comprehensive health care coverage, tuition assistance, and other benefits; however, not all who desire to serve in the US Military are eligible to join. The Department of Defense (DoD) maintains fitness and health requirements (ie, accession standards), which are codified in DoD Instruction 6130.03, Volume 1,¹ that help ensure potential recruits can safely and fully perform their military duties. These accession standards change over time with the evolving understanding of diseases, medical advances, and accrued experience conducting operations in various environments. Accession standards serve to both preserve the health of the applicant and to ensure military mission success.

Dermatologic diseases have been prevalent in conflicts throughout US military history, representing a considerable source of morbidity to service members, inability of service members to remain on active duty, and costly use of resources. Hospitalizations of US Army soldiers for skin conditions led to the loss of more than 2 million days of service in World War I.² In World War II, skin diseases made up 25% and 75% of all temperate and tropical climate visits, respectively. Cutaneous diseases were the most frequently addressed category for US service members in Vietnam, representing more than 1.5 million visits and nearly 10% of disease-related evacuations.² Skin disease remains vital in 21st-century conflict. At a military hospital in Afghanistan, a review of 2421 outpatient medical records from June through July 2007 identified that dermatologic conditions resulted in 20% of military patient evaluations, 7% of nontraumatic hospital admissions, and 2% of total patient evacuations, at an estimated cost of $80,000 per evacuee.³ Between 2003 and 2006, 918 service members were evacuated for dermatologic reasons from combat zones in Afghanistan and Iraq.⁴

Unpredictable military environments may result in flares of a previously controlled condition, new skin diseases, or infection with endemic diseases. Mild cases of common conditions such as psoriasis or atopic dermatitis can present an unacceptable risk for severe flare in the setting of deployed military operations.⁵ Personnel may face extremes in temperature and humidity and work long hours under stress with limited or nonexistent opportunities for hygiene or self-care. Shared equipment and close living quarters permit the spread of infectious diseases and complicate the treatment of infestations. Military equipment and supplies such as gas masks and insect repellents can contain compounds that act as irritants or sensitizing agents, leading to contact dermatitis or urticaria. When dermatologic conditions develop or flare, further challenges are associated with evaluation and management. Health care resources vary considerably by location, with potential limitations in the availability of medications; supplies; refrigeration capabilities; and laboratory, microbiology, and histology services. Furthermore, dermatology referrals and services typically are not feasible in most deployed settings,³ though teledermatology has been available in the armed forces since 2002.

Deployed environments compound the consequences of dermatologic conditions and can impact the military mission. Military units deploy with the number of personnel needed to complete a mission and cannot replace members who become ill or injured or are medically evacuated. Something seemingly trivial, such as poor sleep due to pruritic dermatitis, may impair daytime alertness with potentially grave consequences in critical tasks such as guard or flying duties. The evacuation of a service member can compromise those left behind, and losing a service member with a unique required skill set may jeopardize a unit’s chance of success. Additionally, the impact of an evacuation itself extends beyond its direct cost and effects on the service member’s unit. The military does not maintain dedicated medical evacuation aircraft, instead repurposing aircraft in the deployed setting as needed.⁶ Evacuations can delay flights initially scheduled to move troops, ammunition, food, or other supplies and equipment elsewhere.

Disqualifying Skin and Soft Tissue Conditions

Current accession standards, which are listed in a publicly released document (DoD Instruction 6130.03, Volume 1), are updated based on medical, societal, and technical advances.¹ These standards differ from retention standards, which apply to members actively serving in the military. Although the DoD creates a minimum standard for the entire military, the US Army, Navy, and Air Force adopt these standards and adjust as required for each branch’s needs. An updated copy can be found on the DoD Directives Division website (https://www.esd.whs.mil/dd/) or Med Standards, a third-party mobile application (app) available as a free download for Apple iOS and Android devices (https://www.doc-apps.com/). The app also includes each military branch’s interpretation of the requirements.

The accession standards outline medical conditions that, if present or verified in an applicant’s medical history, preclude joining the military (eTable). These standards are organized into general systems, with a section dedicated to dermatologic (skin and soft tissue) conditions.¹ When a candidate has a potentially disqualifying medical condition identified by a screening questionnaire, medical record review, or military entrance physical examination, a referral for a determination of fitness for duty may be required. Medical accession standards are not solely driven by the diagnosis but also by the extent, nature, and timing of medical management. Procedures or prescriptions requiring frequent clinical monitoring, special handling, or severe dietary restrictions may deem the applicant’s condition potentially unsuitable. The need for immunosuppressive, anticoagulant, or refrigerated medications can impact a patient’s eligibility due to future deployment requirements and suitability for prolonged service, especially if treated for any substantial length of time. Chronic dermatologic conditions that are unresponsive to treatment, are susceptible to exacerbation despite treatment, require regular follow-up care, or interfere with the wear of military gear may be inconsistent with future deployment standards. Although the dermatologist should primarily focus on the skin and soft tissue conditions section of the accession standards, some dermatologic conditions can overlap with other medical systems and be located in a different section; for example, the section on lower extremity conditions includes a disqualifying condition of “[c]urrent ingrown toenails, if infected or symptomatic.”¹

Waiver Process

Medical conditions listed in the accession standards are deemed ineligible for military service; however, applicants can apply for a waiver.¹ The goal is for service members to be well controlled without treatment or with treatment widely available at military clinics and hospitals. Waivers ensure that service members are “[m]edically capable of performing duties without aggravating physical defects or medical conditions,” are “[m]edically adaptable to the military environment without geographical area limitations,” and are “free of medical conditions or physical defects that may reasonably be expected to require excessive time lost from duty for necessary treatment or hospitalization, or may result in separation from the Military Service for unfitness.”¹ The waiver process requires an evaluation from specialists with verification and documentation but does not guarantee approval. Although each military branch follows the same guidelines for disqualifying medical conditions, the evaluation and waiver process varies.

Considerations for Civilian Dermatologists

For several reasons, accurate and detailed medical documentation is essential for patients who pursue military service. Applicants must complete detailed health questionnaires and may need to provide copies of health records. The military electronic health record connects to large civilian health information exchanges and pulls primary documentation from records at many hospitals and clinics. Although applicants may request supportive clarification from their dermatologists, the military relies on primary medical documentation throughout the recruitment process. Accurate diagnostic codes reduce ambiguity, as accession standards are organized by diagnosis; for example, an unspecified history of psoriasis disqualifies applicants unless documentation supports nonrecurrent childhood guttate psoriasis.¹ Clear documentation of symptom severity, response to treatment, or resolution of a condition may elucidate suitability for service when matching a potentially disqualifying condition to a standard is not straightforward. Correct documentation will ensure that potential service members achieve a waiver when it is appropriate. If they are found to be unfit, it may save a patient from a bad outcome or a military unit from mission failure.

Dermatologists in the United States can reference current military medical accession standards to guide patients when needed. For example, a prospective recruit may be hesitant to start isotretinoin for severe nodulocystic acne, concerned that this medication may preclude them from joining the military. The current standards state that “[a]pplicants under treatment with systemic retinoids . . . do not meet the standard until 4 weeks after completing therapy,” while active severe nodulocystic acne is a disqualifying condition.¹ Therefore, the patient could proceed with isotretinoin therapy and, pending clinical response, meet accession standards as soon as 4 weeks after treatment. A clear understanding of the purpose of these standards, including protecting the applicant’s health and maximizing the chance of combat mission accomplishment, helps to reinforce responsibilities when caring for patients who wish to serve.

Purpose of Medical Standards in the US Military

Young adults in the United States traditionally have viewed military service as a viable career given its stable salary, career training, opportunities for progression, comprehensive health care coverage, tuition assistance, and other benefits; however, not all who desire to serve in the US Military are eligible to join. The Department of Defense (DoD) maintains fitness and health requirements (ie, accession standards), which are codified in DoD Instruction 6130.03, Volume 1,¹ that help ensure potential recruits can safely and fully perform their military duties. These accession standards change over time with the evolving understanding of diseases, medical advances, and accrued experience conducting operations in various environments. Accession standards serve to both preserve the health of the applicant and to ensure military mission success.

Dermatologic diseases have been prevalent in conflicts throughout US military history, representing a considerable source of morbidity to service members, inability of service members to remain on active duty, and costly use of resources. Hospitalizations of US Army soldiers for skin conditions led to the loss of more than 2 million days of service in World War I.² In World War II, skin diseases made up 25% and 75% of all temperate and tropical climate visits, respectively. Cutaneous diseases were the most frequently addressed category for US service members in Vietnam, representing more than 1.5 million visits and nearly 10% of disease-related evacuations.² Skin disease remains vital in 21st-century conflict. At a military hospital in Afghanistan, a review of 2421 outpatient medical records from June through July 2007 identified that dermatologic conditions resulted in 20% of military patient evaluations, 7% of nontraumatic hospital admissions, and 2% of total patient evacuations, at an estimated cost of $80,000 per evacuee.³ Between 2003 and 2006, 918 service members were evacuated for dermatologic reasons from combat zones in Afghanistan and Iraq.⁴

Unpredictable military environments may result in flares of a previously controlled condition, new skin diseases, or infection with endemic diseases. Mild cases of common conditions such as psoriasis or atopic dermatitis can present an unacceptable risk for severe flare in the setting of deployed military operations.⁵ Personnel may face extremes in temperature and humidity and work long hours under stress with limited or nonexistent opportunities for hygiene or self-care. Shared equipment and close living quarters permit the spread of infectious diseases and complicate the treatment of infestations. Military equipment and supplies such as gas masks and insect repellents can contain compounds that act as irritants or sensitizing agents, leading to contact dermatitis or urticaria. When dermatologic conditions develop or flare, further challenges are associated with evaluation and management. Health care resources vary considerably by location, with potential limitations in the availability of medications; supplies; refrigeration capabilities; and laboratory, microbiology, and histology services. Furthermore, dermatology referrals and services typically are not feasible in most deployed settings,³ though teledermatology has been available in the armed forces since 2002.

Deployed environments compound the consequences of dermatologic conditions and can impact the military mission. Military units deploy with the number of personnel needed to complete a mission and cannot replace members who become ill or injured or are medically evacuated. Something seemingly trivial, such as poor sleep due to pruritic dermatitis, may impair daytime alertness with potentially grave consequences in critical tasks such as guard or flying duties. The evacuation of a service member can compromise those left behind, and losing a service member with a unique required skill set may jeopardize a unit’s chance of success. Additionally, the impact of an evacuation itself extends beyond its direct cost and effects on the service member’s unit. The military does not maintain dedicated medical evacuation aircraft, instead repurposing aircraft in the deployed setting as needed.⁶ Evacuations can delay flights initially scheduled to move troops, ammunition, food, or other supplies and equipment elsewhere.

Disqualifying Skin and Soft Tissue Conditions

Current accession standards, which are listed in a publicly released document (DoD Instruction 6130.03, Volume 1), are updated based on medical, societal, and technical advances.¹ These standards differ from retention standards, which apply to members actively serving in the military. Although the DoD creates a minimum standard for the entire military, the US Army, Navy, and Air Force adopt these standards and adjust as required for each branch’s needs. An updated copy can be found on the DoD Directives Division website (https://www.esd.whs.mil/dd/) or Med Standards, a third-party mobile application (app) available as a free download for Apple iOS and Android devices (https://www.doc-apps.com/). The app also includes each military branch’s interpretation of the requirements.

The accession standards outline medical conditions that, if present or verified in an applicant’s medical history, preclude joining the military (eTable). These standards are organized into general systems, with a section dedicated to dermatologic (skin and soft tissue) conditions.¹ When a candidate has a potentially disqualifying medical condition identified by a screening questionnaire, medical record review, or military entrance physical examination, a referral for a determination of fitness for duty may be required. Medical accession standards are not solely driven by the diagnosis but also by the extent, nature, and timing of medical management. Procedures or prescriptions requiring frequent clinical monitoring, special handling, or severe dietary restrictions may deem the applicant’s condition potentially unsuitable. The need for immunosuppressive, anticoagulant, or refrigerated medications can impact a patient’s eligibility due to future deployment requirements and suitability for prolonged service, especially if treated for any substantial length of time. Chronic dermatologic conditions that are unresponsive to treatment, are susceptible to exacerbation despite treatment, require regular follow-up care, or interfere with the wear of military gear may be inconsistent with future deployment standards. Although the dermatologist should primarily focus on the skin and soft tissue conditions section of the accession standards, some dermatologic conditions can overlap with other medical systems and be located in a different section; for example, the section on lower extremity conditions includes a disqualifying condition of “[c]urrent ingrown toenails, if infected or symptomatic.”¹

Waiver Process

Medical conditions listed in the accession standards are deemed ineligible for military service; however, applicants can apply for a waiver.¹ The goal is for service members to be well controlled without treatment or with treatment widely available at military clinics and hospitals. Waivers ensure that service members are “[m]edically capable of performing duties without aggravating physical defects or medical conditions,” are “[m]edically adaptable to the military environment without geographical area limitations,” and are “free of medical conditions or physical defects that may reasonably be expected to require excessive time lost from duty for necessary treatment or hospitalization, or may result in separation from the Military Service for unfitness.”¹ The waiver process requires an evaluation from specialists with verification and documentation but does not guarantee approval. Although each military branch follows the same guidelines for disqualifying medical conditions, the evaluation and waiver process varies.

Considerations for Civilian Dermatologists

For several reasons, accurate and detailed medical documentation is essential for patients who pursue military service. Applicants must complete detailed health questionnaires and may need to provide copies of health records. The military electronic health record connects to large civilian health information exchanges and pulls primary documentation from records at many hospitals and clinics. Although applicants may request supportive clarification from their dermatologists, the military relies on primary medical documentation throughout the recruitment process. Accurate diagnostic codes reduce ambiguity, as accession standards are organized by diagnosis; for example, an unspecified history of psoriasis disqualifies applicants unless documentation supports nonrecurrent childhood guttate psoriasis.¹ Clear documentation of symptom severity, response to treatment, or resolution of a condition may elucidate suitability for service when matching a potentially disqualifying condition to a standard is not straightforward. Correct documentation will ensure that potential service members achieve a waiver when it is appropriate. If they are found to be unfit, it may save a patient from a bad outcome or a military unit from mission failure.

Dermatologists in the United States can reference current military medical accession standards to guide patients when needed. For example, a prospective recruit may be hesitant to start isotretinoin for severe nodulocystic acne, concerned that this medication may preclude them from joining the military. The current standards state that “[a]pplicants under treatment with systemic retinoids . . . do not meet the standard until 4 weeks after completing therapy,” while active severe nodulocystic acne is a disqualifying condition.¹ Therefore, the patient could proceed with isotretinoin therapy and, pending clinical response, meet accession standards as soon as 4 weeks after treatment. A clear understanding of the purpose of these standards, including protecting the applicant’s health and maximizing the chance of combat mission accomplishment, helps to reinforce responsibilities when caring for patients who wish to serve.

Purpose of Medical Standards in the US Military

Young adults in the United States traditionally have viewed military service as a viable career given its stable salary, career training, opportunities for progression, comprehensive health care coverage, tuition assistance, and other benefits; however, not all who desire to serve in the US Military are eligible to join. The Department of Defense (DoD) maintains fitness and health requirements (ie, accession standards), which are codified in DoD Instruction 6130.03, Volume 1,¹ that help ensure potential recruits can safely and fully perform their military duties. These accession standards change over time with the evolving understanding of diseases, medical advances, and accrued experience conducting operations in various environments. Accession standards serve to both preserve the health of the applicant and to ensure military mission success.

Dermatologic diseases have been prevalent in conflicts throughout US military history, representing a considerable source of morbidity to service members, inability of service members to remain on active duty, and costly use of resources. Hospitalizations of US Army soldiers for skin conditions led to the loss of more than 2 million days of service in World War I.² In World War II, skin diseases made up 25% and 75% of all temperate and tropical climate visits, respectively. Cutaneous diseases were the most frequently addressed category for US service members in Vietnam, representing more than 1.5 million visits and nearly 10% of disease-related evacuations.² Skin disease remains vital in 21st-century conflict. At a military hospital in Afghanistan, a review of 2421 outpatient medical records from June through July 2007 identified that dermatologic conditions resulted in 20% of military patient evaluations, 7% of nontraumatic hospital admissions, and 2% of total patient evacuations, at an estimated cost of $80,000 per evacuee.³ Between 2003 and 2006, 918 service members were evacuated for dermatologic reasons from combat zones in Afghanistan and Iraq.⁴

Unpredictable military environments may result in flares of a previously controlled condition, new skin diseases, or infection with endemic diseases. Mild cases of common conditions such as psoriasis or atopic dermatitis can present an unacceptable risk for severe flare in the setting of deployed military operations.⁵ Personnel may face extremes in temperature and humidity and work long hours under stress with limited or nonexistent opportunities for hygiene or self-care. Shared equipment and close living quarters permit the spread of infectious diseases and complicate the treatment of infestations. Military equipment and supplies such as gas masks and insect repellents can contain compounds that act as irritants or sensitizing agents, leading to contact dermatitis or urticaria. When dermatologic conditions develop or flare, further challenges are associated with evaluation and management. Health care resources vary considerably by location, with potential limitations in the availability of medications; supplies; refrigeration capabilities; and laboratory, microbiology, and histology services. Furthermore, dermatology referrals and services typically are not feasible in most deployed settings,³ though teledermatology has been available in the armed forces since 2002.

Deployed environments compound the consequences of dermatologic conditions and can impact the military mission. Military units deploy with the number of personnel needed to complete a mission and cannot replace members who become ill or injured or are medically evacuated. Something seemingly trivial, such as poor sleep due to pruritic dermatitis, may impair daytime alertness with potentially grave consequences in critical tasks such as guard or flying duties. The evacuation of a service member can compromise those left behind, and losing a service member with a unique required skill set may jeopardize a unit’s chance of success. Additionally, the impact of an evacuation itself extends beyond its direct cost and effects on the service member’s unit. The military does not maintain dedicated medical evacuation aircraft, instead repurposing aircraft in the deployed setting as needed.⁶ Evacuations can delay flights initially scheduled to move troops, ammunition, food, or other supplies and equipment elsewhere.

Disqualifying Skin and Soft Tissue Conditions

Current accession standards, which are listed in a publicly released document (DoD Instruction 6130.03, Volume 1), are updated based on medical, societal, and technical advances.¹ These standards differ from retention standards, which apply to members actively serving in the military. Although the DoD creates a minimum standard for the entire military, the US Army, Navy, and Air Force adopt these standards and adjust as required for each branch’s needs. An updated copy can be found on the DoD Directives Division website (https://www.esd.whs.mil/dd/) or Med Standards, a third-party mobile application (app) available as a free download for Apple iOS and Android devices (https://www.doc-apps.com/). The app also includes each military branch’s interpretation of the requirements.

The accession standards outline medical conditions that, if present or verified in an applicant’s medical history, preclude joining the military (eTable). These standards are organized into general systems, with a section dedicated to dermatologic (skin and soft tissue) conditions.¹ When a candidate has a potentially disqualifying medical condition identified by a screening questionnaire, medical record review, or military entrance physical examination, a referral for a determination of fitness for duty may be required. Medical accession standards are not solely driven by the diagnosis but also by the extent, nature, and timing of medical management. Procedures or prescriptions requiring frequent clinical monitoring, special handling, or severe dietary restrictions may deem the applicant’s condition potentially unsuitable. The need for immunosuppressive, anticoagulant, or refrigerated medications can impact a patient’s eligibility due to future deployment requirements and suitability for prolonged service, especially if treated for any substantial length of time. Chronic dermatologic conditions that are unresponsive to treatment, are susceptible to exacerbation despite treatment, require regular follow-up care, or interfere with the wear of military gear may be inconsistent with future deployment standards. Although the dermatologist should primarily focus on the skin and soft tissue conditions section of the accession standards, some dermatologic conditions can overlap with other medical systems and be located in a different section; for example, the section on lower extremity conditions includes a disqualifying condition of “[c]urrent ingrown toenails, if infected or symptomatic.”¹

Waiver Process

Medical conditions listed in the accession standards are deemed ineligible for military service; however, applicants can apply for a waiver.¹ The goal is for service members to be well controlled without treatment or with treatment widely available at military clinics and hospitals. Waivers ensure that service members are “[m]edically capable of performing duties without aggravating physical defects or medical conditions,” are “[m]edically adaptable to the military environment without geographical area limitations,” and are “free of medical conditions or physical defects that may reasonably be expected to require excessive time lost from duty for necessary treatment or hospitalization, or may result in separation from the Military Service for unfitness.”¹ The waiver process requires an evaluation from specialists with verification and documentation but does not guarantee approval. Although each military branch follows the same guidelines for disqualifying medical conditions, the evaluation and waiver process varies.

Considerations for Civilian Dermatologists

For several reasons, accurate and detailed medical documentation is essential for patients who pursue military service. Applicants must complete detailed health questionnaires and may need to provide copies of health records. The military electronic health record connects to large civilian health information exchanges and pulls primary documentation from records at many hospitals and clinics. Although applicants may request supportive clarification from their dermatologists, the military relies on primary medical documentation throughout the recruitment process. Accurate diagnostic codes reduce ambiguity, as accession standards are organized by diagnosis; for example, an unspecified history of psoriasis disqualifies applicants unless documentation supports nonrecurrent childhood guttate psoriasis.¹ Clear documentation of symptom severity, response to treatment, or resolution of a condition may elucidate suitability for service when matching a potentially disqualifying condition to a standard is not straightforward. Correct documentation will ensure that potential service members achieve a waiver when it is appropriate. If they are found to be unfit, it may save a patient from a bad outcome or a military unit from mission failure.

Dermatologists in the United States can reference current military medical accession standards to guide patients when needed. For example, a prospective recruit may be hesitant to start isotretinoin for severe nodulocystic acne, concerned that this medication may preclude them from joining the military. The current standards state that “[a]pplicants under treatment with systemic retinoids . . . do not meet the standard until 4 weeks after completing therapy,” while active severe nodulocystic acne is a disqualifying condition.¹ Therefore, the patient could proceed with isotretinoin therapy and, pending clinical response, meet accession standards as soon as 4 weeks after treatment. A clear understanding of the purpose of these standards, including protecting the applicant’s health and maximizing the chance of combat mission accomplishment, helps to reinforce responsibilities when caring for patients who wish to serve.

Practice Gap

Repair of a conchal defect requires careful consideration to achieve an optimal outcome. Reconstruction should resurface exposed cartilage, restore the natural projection of the auricle, and direct sound into the external auditory meatus. Patients also should be able to wear glasses and a hearing aid.

The reconstructive ladder for most conchal bowl defects includes secondary intention healing, full-thickness skin grafting (FTSG), and either a revolving-door flap or a flip-flop flap. Secondary intention and FTSG are appropriate for superficial defects, in which the loss of cartilage is not substantial.^1,2 Revolving-door and flip-flop flaps are single-stage retroauricular approaches used to repair relatively small defects of the conchal bowl.³ However, reconstructive options are limited for a large defect in which there is extensive loss of cartilage; 3-stage retroauricular approaches have been utilized. The anterior pedicled retroauricular flap is a 3-stage repair that can be utilized to reconstruct a through-and-through defect of the central ear:

• Stage 1: an anteriorly based retroauricular pedicle is incised, hinged over, and sutured to the medial aspect of the defect, resurfacing the posterior ear.
• Stage 2: the pedicle is severed and the flap is folded on itself to resurface the anterior ear.
• Stage 3: the folded edge is de-epithelialized and set into the lateral defect.⁴

The revolving-door flap also uses a 3-stage approach and is utilized for a full-thickness central auricular defect:

• Stage 1: a revolving-door flap is used to resurface the anterior ear.
• Stage 2: a cartilage graft provides structural support.
• Stage 3: division and inset with an FTSG is used to resurface the posterior ear.

The anterior pedicled retroauricular flap and revolving-door flap techniques are useful for defects when there is intact posterior auricular skin but not when there is extensive loss of cartilage. Other downsides to these 3-stage approaches are the time and multiple procedures required.⁵

We describe the technique of a retroauricular pull-through sandwich flap for repair of a large conchal bowl defect with extensive cartilage loss and intact posterior auricular skin.

Technique

A 62-year-old man presented for treatment of a 2.6×2.4-cm nodular and infiltrative basal cell carcinoma of the right conchal bowl. The tumor was cleared with 3 stages of Mohs micrographic surgery, resulting in a 5.5×4.2-cm defect with complete loss of cartilage throughout the concha, helical crus, and inner rim of the antihelix (Figure 1). A 2-stage repair was performed utilizing a cartilage graft and a pull-through retroauricular interpolation flap.

Stage 1—A cartilage graft was harvested from the left concha and sutured into the central defect for structural support (Figure 2). An incision was then made through the posterior auricular skin, just medial to the residual antihelical cartilage, and a retroauricular interpolation flap was pulled through this incision to resurface the lateral two-thirds of the conchal bowl defect. This created a “sandwich” of tissue, with the following layers (ordered from anterior to posterior): retroauricular interpolation flap, cartilage graft, and intact posterior auricular skin.

A preauricular banner transposition flap was used to repair the medial one-third of the conchal defect. A small area was left to heal by secondary intention (Figure 3).

Stage 2—The patient returned 3 weeks later for division and inset of the retroauricular interpolation flap. The pedicle of the flap was severed and its free edge was sutured into the lateral aspect of the defect. The posterior auricular incision that the flap had been pulled through in stage 1 of the repair was closed in a layered fashion, and the secondary defect of the postauricular scalp was left to heal by secondary intention (Figure 4).

Final Results—At follow-up 1 month later, the patient was noted to have good aesthetic and functional outcomes (Figure 5).

Practice Implications

The retroauricular pull-through sandwich flap combines a cartilage graft and a retroauricular interpolation flap pulled through an incision in the posterior auricular skin to resurface the anterior ear. This repair is most useful for a large conchal bowl defect in which there is extensive missing cartilage but intact posterior auricular skin.

The retroauricular scalp is a substantial tissue reservoir with robust vasculature; an interpolation flap from this area frequently is used to repair an extensive ear defect. The most common use of an interpolation flap is for a large helical defect; however, the flap also can be pulled through an incision in the posterior auricular skin to the front of the ear in a manner similar to revolving-door and flip-flop flaps, thus allowing for increased flap reach.

A cartilage graft provides structural support, helping to maintain auricular projection. The helical arcades provide a robust vascular supply and maintain viability of the helical rim tissue, despite the large aperture created for the pull-through flap.

We recommend this 2-stage repair for large conchal bowl defects with extensive cartilage loss and intact posterior auricular skin.

Practice Gap

Repair of a conchal defect requires careful consideration to achieve an optimal outcome. Reconstruction should resurface exposed cartilage, restore the natural projection of the auricle, and direct sound into the external auditory meatus. Patients also should be able to wear glasses and a hearing aid.

The reconstructive ladder for most conchal bowl defects includes secondary intention healing, full-thickness skin grafting (FTSG), and either a revolving-door flap or a flip-flop flap. Secondary intention and FTSG are appropriate for superficial defects, in which the loss of cartilage is not substantial.^1,2 Revolving-door and flip-flop flaps are single-stage retroauricular approaches used to repair relatively small defects of the conchal bowl.³ However, reconstructive options are limited for a large defect in which there is extensive loss of cartilage; 3-stage retroauricular approaches have been utilized. The anterior pedicled retroauricular flap is a 3-stage repair that can be utilized to reconstruct a through-and-through defect of the central ear:

• Stage 1: an anteriorly based retroauricular pedicle is incised, hinged over, and sutured to the medial aspect of the defect, resurfacing the posterior ear.
• Stage 2: the pedicle is severed and the flap is folded on itself to resurface the anterior ear.
• Stage 3: the folded edge is de-epithelialized and set into the lateral defect.⁴

The revolving-door flap also uses a 3-stage approach and is utilized for a full-thickness central auricular defect:

• Stage 1: a revolving-door flap is used to resurface the anterior ear.
• Stage 2: a cartilage graft provides structural support.
• Stage 3: division and inset with an FTSG is used to resurface the posterior ear.

The anterior pedicled retroauricular flap and revolving-door flap techniques are useful for defects when there is intact posterior auricular skin but not when there is extensive loss of cartilage. Other downsides to these 3-stage approaches are the time and multiple procedures required.⁵

We describe the technique of a retroauricular pull-through sandwich flap for repair of a large conchal bowl defect with extensive cartilage loss and intact posterior auricular skin.

Technique

A 62-year-old man presented for treatment of a 2.6×2.4-cm nodular and infiltrative basal cell carcinoma of the right conchal bowl. The tumor was cleared with 3 stages of Mohs micrographic surgery, resulting in a 5.5×4.2-cm defect with complete loss of cartilage throughout the concha, helical crus, and inner rim of the antihelix (Figure 1). A 2-stage repair was performed utilizing a cartilage graft and a pull-through retroauricular interpolation flap.

Stage 1—A cartilage graft was harvested from the left concha and sutured into the central defect for structural support (Figure 2). An incision was then made through the posterior auricular skin, just medial to the residual antihelical cartilage, and a retroauricular interpolation flap was pulled through this incision to resurface the lateral two-thirds of the conchal bowl defect. This created a “sandwich” of tissue, with the following layers (ordered from anterior to posterior): retroauricular interpolation flap, cartilage graft, and intact posterior auricular skin.

A preauricular banner transposition flap was used to repair the medial one-third of the conchal defect. A small area was left to heal by secondary intention (Figure 3).

Stage 2—The patient returned 3 weeks later for division and inset of the retroauricular interpolation flap. The pedicle of the flap was severed and its free edge was sutured into the lateral aspect of the defect. The posterior auricular incision that the flap had been pulled through in stage 1 of the repair was closed in a layered fashion, and the secondary defect of the postauricular scalp was left to heal by secondary intention (Figure 4).

Final Results—At follow-up 1 month later, the patient was noted to have good aesthetic and functional outcomes (Figure 5).

Practice Implications

The retroauricular pull-through sandwich flap combines a cartilage graft and a retroauricular interpolation flap pulled through an incision in the posterior auricular skin to resurface the anterior ear. This repair is most useful for a large conchal bowl defect in which there is extensive missing cartilage but intact posterior auricular skin.

The retroauricular scalp is a substantial tissue reservoir with robust vasculature; an interpolation flap from this area frequently is used to repair an extensive ear defect. The most common use of an interpolation flap is for a large helical defect; however, the flap also can be pulled through an incision in the posterior auricular skin to the front of the ear in a manner similar to revolving-door and flip-flop flaps, thus allowing for increased flap reach.

A cartilage graft provides structural support, helping to maintain auricular projection. The helical arcades provide a robust vascular supply and maintain viability of the helical rim tissue, despite the large aperture created for the pull-through flap.

We recommend this 2-stage repair for large conchal bowl defects with extensive cartilage loss and intact posterior auricular skin.

Practice Gap

Repair of a conchal defect requires careful consideration to achieve an optimal outcome. Reconstruction should resurface exposed cartilage, restore the natural projection of the auricle, and direct sound into the external auditory meatus. Patients also should be able to wear glasses and a hearing aid.

The reconstructive ladder for most conchal bowl defects includes secondary intention healing, full-thickness skin grafting (FTSG), and either a revolving-door flap or a flip-flop flap. Secondary intention and FTSG are appropriate for superficial defects, in which the loss of cartilage is not substantial.^1,2 Revolving-door and flip-flop flaps are single-stage retroauricular approaches used to repair relatively small defects of the conchal bowl.³ However, reconstructive options are limited for a large defect in which there is extensive loss of cartilage; 3-stage retroauricular approaches have been utilized. The anterior pedicled retroauricular flap is a 3-stage repair that can be utilized to reconstruct a through-and-through defect of the central ear:

• Stage 1: an anteriorly based retroauricular pedicle is incised, hinged over, and sutured to the medial aspect of the defect, resurfacing the posterior ear.
• Stage 2: the pedicle is severed and the flap is folded on itself to resurface the anterior ear.
• Stage 3: the folded edge is de-epithelialized and set into the lateral defect.⁴

The revolving-door flap also uses a 3-stage approach and is utilized for a full-thickness central auricular defect:

• Stage 1: a revolving-door flap is used to resurface the anterior ear.
• Stage 2: a cartilage graft provides structural support.
• Stage 3: division and inset with an FTSG is used to resurface the posterior ear.

The anterior pedicled retroauricular flap and revolving-door flap techniques are useful for defects when there is intact posterior auricular skin but not when there is extensive loss of cartilage. Other downsides to these 3-stage approaches are the time and multiple procedures required.⁵

We describe the technique of a retroauricular pull-through sandwich flap for repair of a large conchal bowl defect with extensive cartilage loss and intact posterior auricular skin.

Technique

A 62-year-old man presented for treatment of a 2.6×2.4-cm nodular and infiltrative basal cell carcinoma of the right conchal bowl. The tumor was cleared with 3 stages of Mohs micrographic surgery, resulting in a 5.5×4.2-cm defect with complete loss of cartilage throughout the concha, helical crus, and inner rim of the antihelix (Figure 1). A 2-stage repair was performed utilizing a cartilage graft and a pull-through retroauricular interpolation flap.

Stage 1—A cartilage graft was harvested from the left concha and sutured into the central defect for structural support (Figure 2). An incision was then made through the posterior auricular skin, just medial to the residual antihelical cartilage, and a retroauricular interpolation flap was pulled through this incision to resurface the lateral two-thirds of the conchal bowl defect. This created a “sandwich” of tissue, with the following layers (ordered from anterior to posterior): retroauricular interpolation flap, cartilage graft, and intact posterior auricular skin.

A preauricular banner transposition flap was used to repair the medial one-third of the conchal defect. A small area was left to heal by secondary intention (Figure 3).

Stage 2—The patient returned 3 weeks later for division and inset of the retroauricular interpolation flap. The pedicle of the flap was severed and its free edge was sutured into the lateral aspect of the defect. The posterior auricular incision that the flap had been pulled through in stage 1 of the repair was closed in a layered fashion, and the secondary defect of the postauricular scalp was left to heal by secondary intention (Figure 4).

Final Results—At follow-up 1 month later, the patient was noted to have good aesthetic and functional outcomes (Figure 5).

Practice Implications

The retroauricular pull-through sandwich flap combines a cartilage graft and a retroauricular interpolation flap pulled through an incision in the posterior auricular skin to resurface the anterior ear. This repair is most useful for a large conchal bowl defect in which there is extensive missing cartilage but intact posterior auricular skin.

The retroauricular scalp is a substantial tissue reservoir with robust vasculature; an interpolation flap from this area frequently is used to repair an extensive ear defect. The most common use of an interpolation flap is for a large helical defect; however, the flap also can be pulled through an incision in the posterior auricular skin to the front of the ear in a manner similar to revolving-door and flip-flop flaps, thus allowing for increased flap reach.

A cartilage graft provides structural support, helping to maintain auricular projection. The helical arcades provide a robust vascular supply and maintain viability of the helical rim tissue, despite the large aperture created for the pull-through flap.

We recommend this 2-stage repair for large conchal bowl defects with extensive cartilage loss and intact posterior auricular skin.

Interim follow-up data from the A041702 phase-3 clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (June 2-6) indicates that the addition of venetoclax (V) to ibrutinib + obinutuzumab (IO) to treat chronic lymphocytic leukemia (CLL) does not increase short- or medium-term progression-free survival (PFS) in older patients. The difference in PFS between the IVO arm, 85%, versus 87% in the IO arm was statistically insignificant.

“Due to the early read-out and the futility boundaries being crossed, long-term follow-up will be critical to understand if there are any long-term benefits to IVO,” said study principal investigator Jennifer A. Woyach MD, professor in the division of hematology at The Ohio State University Comprehensive Care Center (OSUCCC – The James) in Columbus.

The Ohio State University Comprehensive Care Center

The 14-month follow-up data includes results from 465 CLL patients aged 65+ (median age 74 years, 67.5% male) who were treatment naive. The IO and IVO arms had 232 and 233 participants respectively, patients across both arms had Eastern Cooperative Oncology Group scores of 0-1 (97%), occurrence of Del (17p) was 13%, and a Rai stage status of III/IV was 55%, slightly more patients in the IO arm had unmutated IGHV 55% vs. 47% in the IVO arm. Researchers noted that, as expected, patients in the IVO group had a greater occurrence of hematologic adverse events graded at 3 or above, 61% VS 48% in the IO arm, P =.006.

The trial was spurred by the fact that many CLL patients on IO therapy must remain on treatment indefinitely, and an earlier phase II trial suggested that IVO therapy could lead to deep remission and therapy discontinuation.

Looking at the complete response (CR) rates and undetectable minimal residual disease (uMRD) rates across both arms suggested that there may be some hope that IVO could help CLL patients achieve deep remissions and discontinue therapy. Patients in the IVO arm had a CR of 68.5% and uMRD of 86.8% while only 31.3% of those in the IO arm had a CR and 33.3% achieved uMRD status.

“Despite the impressive CR and uMRD results, this study demonstrates that IVO is not superior to IO in terms of progression-free survival. However, because many patients in the IVO arm have discontinued treatment while those in the IO arm remain on ibrutinib, we think that it will be very important to continue to follow these patients long term, to see if there are advantages to this time limited therapy, especially in terms of toxicity, that we cannot appreciate with this follow-up,” said Dr. Woyach.

The Alliance for Clinical Trials in Oncology cooperative group, including OSUCCC James, is currently working to design the next frontline CLL study for older patients that builds on this work.

Dr. Woyach disclosed ties with Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics, and Schrodinger.

Interim follow-up data from the A041702 phase-3 clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (June 2-6) indicates that the addition of venetoclax (V) to ibrutinib + obinutuzumab (IO) to treat chronic lymphocytic leukemia (CLL) does not increase short- or medium-term progression-free survival (PFS) in older patients. The difference in PFS between the IVO arm, 85%, versus 87% in the IO arm was statistically insignificant.

“Due to the early read-out and the futility boundaries being crossed, long-term follow-up will be critical to understand if there are any long-term benefits to IVO,” said study principal investigator Jennifer A. Woyach MD, professor in the division of hematology at The Ohio State University Comprehensive Care Center (OSUCCC – The James) in Columbus.

The Ohio State University Comprehensive Care Center

The 14-month follow-up data includes results from 465 CLL patients aged 65+ (median age 74 years, 67.5% male) who were treatment naive. The IO and IVO arms had 232 and 233 participants respectively, patients across both arms had Eastern Cooperative Oncology Group scores of 0-1 (97%), occurrence of Del (17p) was 13%, and a Rai stage status of III/IV was 55%, slightly more patients in the IO arm had unmutated IGHV 55% vs. 47% in the IVO arm. Researchers noted that, as expected, patients in the IVO group had a greater occurrence of hematologic adverse events graded at 3 or above, 61% VS 48% in the IO arm, P =.006.

The trial was spurred by the fact that many CLL patients on IO therapy must remain on treatment indefinitely, and an earlier phase II trial suggested that IVO therapy could lead to deep remission and therapy discontinuation.

Looking at the complete response (CR) rates and undetectable minimal residual disease (uMRD) rates across both arms suggested that there may be some hope that IVO could help CLL patients achieve deep remissions and discontinue therapy. Patients in the IVO arm had a CR of 68.5% and uMRD of 86.8% while only 31.3% of those in the IO arm had a CR and 33.3% achieved uMRD status.

“Despite the impressive CR and uMRD results, this study demonstrates that IVO is not superior to IO in terms of progression-free survival. However, because many patients in the IVO arm have discontinued treatment while those in the IO arm remain on ibrutinib, we think that it will be very important to continue to follow these patients long term, to see if there are advantages to this time limited therapy, especially in terms of toxicity, that we cannot appreciate with this follow-up,” said Dr. Woyach.

The Alliance for Clinical Trials in Oncology cooperative group, including OSUCCC James, is currently working to design the next frontline CLL study for older patients that builds on this work.

Dr. Woyach disclosed ties with Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics, and Schrodinger.

Interim follow-up data from the A041702 phase-3 clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (June 2-6) indicates that the addition of venetoclax (V) to ibrutinib + obinutuzumab (IO) to treat chronic lymphocytic leukemia (CLL) does not increase short- or medium-term progression-free survival (PFS) in older patients. The difference in PFS between the IVO arm, 85%, versus 87% in the IO arm was statistically insignificant.

“Due to the early read-out and the futility boundaries being crossed, long-term follow-up will be critical to understand if there are any long-term benefits to IVO,” said study principal investigator Jennifer A. Woyach MD, professor in the division of hematology at The Ohio State University Comprehensive Care Center (OSUCCC – The James) in Columbus.

The Ohio State University Comprehensive Care Center

The 14-month follow-up data includes results from 465 CLL patients aged 65+ (median age 74 years, 67.5% male) who were treatment naive. The IO and IVO arms had 232 and 233 participants respectively, patients across both arms had Eastern Cooperative Oncology Group scores of 0-1 (97%), occurrence of Del (17p) was 13%, and a Rai stage status of III/IV was 55%, slightly more patients in the IO arm had unmutated IGHV 55% vs. 47% in the IVO arm. Researchers noted that, as expected, patients in the IVO group had a greater occurrence of hematologic adverse events graded at 3 or above, 61% VS 48% in the IO arm, P =.006.

The trial was spurred by the fact that many CLL patients on IO therapy must remain on treatment indefinitely, and an earlier phase II trial suggested that IVO therapy could lead to deep remission and therapy discontinuation.

Looking at the complete response (CR) rates and undetectable minimal residual disease (uMRD) rates across both arms suggested that there may be some hope that IVO could help CLL patients achieve deep remissions and discontinue therapy. Patients in the IVO arm had a CR of 68.5% and uMRD of 86.8% while only 31.3% of those in the IO arm had a CR and 33.3% achieved uMRD status.

“Despite the impressive CR and uMRD results, this study demonstrates that IVO is not superior to IO in terms of progression-free survival. However, because many patients in the IVO arm have discontinued treatment while those in the IO arm remain on ibrutinib, we think that it will be very important to continue to follow these patients long term, to see if there are advantages to this time limited therapy, especially in terms of toxicity, that we cannot appreciate with this follow-up,” said Dr. Woyach.

The Alliance for Clinical Trials in Oncology cooperative group, including OSUCCC James, is currently working to design the next frontline CLL study for older patients that builds on this work.

Dr. Woyach disclosed ties with Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics, and Schrodinger.

Isotretinoin is used in the treatment of nodulocystic and severe papulopustular acne. During the treatment period, laboratory monitoring is recommended to identify the risk for complications such as hepatotoxicity, teratogenicity, rhabdomyolysis, hyperlipidemia, and pancreatitis.¹ There is a lack of consensus of the frequency of follow-up of laboratory parameters during isotretinoin treatment. This study evaluated the changes in laboratory parameters used in daily practice for patients with acne who were treated with isotretinoin to determine the optimum test repetition frequency.

Materials and Methods

We conducted a retrospective study of data from patients who received oral isotretinoin therapy for acne between January 2021 and July 2022 via the electronic medical records at Konya Numune Hospital and Konya Private Medova Hospital (both in Konya, Turkey). Patients who received an oral isotretinoin total cumulative dose greater than 120 mg/kg were included in the study. Patient demographic data; cumulative isotretinoin doses; and alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), creatinine kinase (CK), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels during treatment were recorded. Baseline laboratory levels of those parameters were compared with levels of the same parameters from the second and fourth months of treatment. Comparisons for all parameters were made between the second- and fourth-month levels. Reference ranges are shown in Table 1. Abnormalities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading system.² This study was approved by the Karatay University (Konya, Turkey) ethical committee.

Statistical Analysis—The descriptive statistics of the measurements were presented as means, standard deviations, or medians (first and third quartiles). With respect to the normal distribution, the consistency of the measurements was evaluated with the Kolmogorov-Smirnov test, and small deviations from the normal distribution were observed. Changes in laboratory measurements were evaluated with simple repeated-measures analysis of variance, and changes that differed significantly were determined by a Holm-Sidak post hoc test. Relationships between total cumulative doses and laboratory measurements at second visits were evaluated by the Pearson correlation analysis. The statistical significance level was P<.05. SPSS Statistics 23 (IBM) was used in the calculations.

Results

Consecutive Data at Baseline and Follow-up—A total of 415 patients with a mean age (SD) of 21.49 (7.25) years (range, 12–53 years) were included in our study. The mean total cumulative dose (SD) of the patients was 7267.27 (1878.4) mg. The consecutive data of the means of the laboratory parameters are shown in Table 1 and Figure 1. There was no significant change in the ALT levels between baseline and the fourth month as well as between the second- and fourth-month assessments (both P=.311). When comparing the differences among AST, GGT, and LDL-C measurements, the levels increased significantly between baseline and the second month and between baseline and the fourth month (all P<.001). There was no significant difference in CK levels at all assessments (all P=.304). When the differences between TG measurements were compared, the changes between baseline and the second month (P<.001), baseline and the fourth month (P<.001), and the second and fourth months (P=.013) were significant (Figure 1).

Abnormal Laboratory Measurements—The distribution of abnormal laboratory measurements during treatment is shown in Table 2 and Figure 2. Grade 3 or higher elevations of liver transaminases (ALT, AST) and GGT were observed in fewer than 2% of patients during treatment compared with baseline (grade 3 elevations of ALT and AST together in 2 patients; grade 4 AST elevation in 1 patient; grade 3 elevations of ALT, AST, and GGT combined in 1 patient; isolated grade 3 GGT elevation in 1 patient). All of the patients who developed grade 3 liver transaminases and isolated grade 3 GGT elevation had improved values when these were rechecked within 2 weeks.

In the patient who developed hepatotoxicity in the second month, the ALT level rose from a baseline of 19 U/L to 169 U/L, the AST level from a baseline of 19 U/L to 61 U/L, and the GGT level from a baseline of 24 U/L to 124 U/L. The patient was asymptomatic. Liver function test levels returned to reference range 4 weeks after discontinuation of therapy. Hepatotoxicity did not recur after treatment was re-administered.

The patient who developed grade 4 AST elevation (364 U/L) experienced fatigue and myalgia. He had done vigorous exercise up to 2 days before the test and also had a grade 4 CK elevation (12,310 U/L). He was thought to have isotretinoin-related rhabdomyolysis. His treatment was discontinued, and he was advised to hydrate and rest. Treatment was re-started after 2 weeks. With frequent laboratory monitoring and avoidance of vigorous physical activity, the patient completed the remaining course of isotretinoin without any laboratory abnormalities or symptoms.

Creatinine kinase abnormalities in the second and fourth months compared with baseline were not statistically significant. The patients with grade 3 or higher CK elevations, except for the case with rhabdomyolysis, had no clinical signs or other characteristic laboratory findings of rhabdomyolysis.

Hypercholesterolemia (LDL-C ≥130 mg/dL) occurred most frequently, with a maximum of 280 mg/dL in 1 patient (in the fourth month) and less than 250 mg/dL in all other patients. Hypercholesterolemia occurred in 183 (44.1%) patients in the second month and in 166 (40.0%) patients in the fourth month. However, baseline abnormalities also were frequent (86 [20.7%]), and hypercholesterolemia persisted in the second and fourth months in all of these patients.

It was observed that the patients with TG abnormalities increased continuously in the second (99 [23.9%]) and fourth (113 [27.2%]) months compared with baseline (49 [11.8%]). Grade 3 TG elevations were observed in 2.2% of patients (n=9; 5 patients in the second month, 4 patients in the fourth month) during treatment compared with baseline, and all patients had grade 1 or 2 hypertriglyceridemia at baseline. Of the patients with grade 3 TG elevation, 3 patients in the second month and 2 patients in the fourth month were obese at baseline. No grade 4 TG elevations were observed. Complications related to hyperlipidemia, such as pancreatitis, were observed in 1 patient. No patient terminated treatment because of lipid abnormalities. The treatment of our patients with major hypercholesterolemia and/or grade 3 hypertriglyceridemia was interrupted. The hyperlipidemia of these patients was controlled by a low-fat diet and a short-term dose reduction.

Relationship Between Total Cumulative Dose and Laboratory Parameters—The relationships between the total cumulative dose and changes up to the fourth month are presented in Table 3. As the total dose increased, the changes in TG and LDL-C levels significantly increased in the fourth month (both P=.001). However, the degree of these relationships was weak. No significant correlation was found between the periodic changes of other laboratory parameters and the total dose.

Comment

The parameters followed in our study show that TG levels tend to increase continuously from baseline during isotretinoin treatment, while ALT, AST, GGT, and LDL-C levels increase in the second month and decrease at 4 months. Although this same trend occurs with CK levels, the change was not statistically significant. The most common laboratory abnormality in our study was hyperlipidemia. Levels of LDL-C and TG were both found to be statistically elevated in the second and fourth months of treatment compared with baseline. Parthasarathy et al³ reported that obesity had an important role in the increase of lipid levels in patients using isotretinoin at baseline. In our study, 5 of 9 patients (55.6%) with grade 3 TG elevation were obese, which supports the theory that obesity plays an important role in the increase in lipid levels. Up-to-date laboratory follow-up of lipids suggests that there is no need to follow up serum lipids after the second month of treatment. Patients with risk factors for hyperlipidemia, such as abdominal obesity and familial hyperlipidemia, do not require further follow-up if there is no increase in serum lipids in the first month of treatment.¹ The presence of grade 1 or 2 hypertriglyceridemia at baseline in all our patients with grade 3 TG elevation may suggest that periodic laboratory follow-up during isotretinoin treatment is necessary to detect patients with grade 3 and higher TG levels.

The lack of knowledge of other risk factors (eg, familial hyperlipidemia, insulin resistance) for hyperlipidemia in all patients at baseline may be a limitation of our study. Although hypercholesterolemia persisted in the follow-up of our patients with initial LDL-C abnormalities, hypercholesterolemia over 250 mg/dL was very rare (1 patient). Possible complications associated with serum lipid abnormalities are pancreatitis and metabolic syndrome.⁴ In our study, none of the patients with lipid abnormalities had any relevant clinical sequelae. The dose-dependent elevation of the changes in LDL-C and TG (Table 3) may be important to predict the significant elevation of lipids and the associated complications in patients with a high total cumulative dose target that may require a long treatment duration. However, considering the short follow-up periods in our patients, the absence of clinical sequelae may be misleading. There are differences in recommendations between the US and European guidelines for isotretinoin dosage. Although the US guidelines recommend a total cumulative dose target, the European guidelines recommend low-dose isotretinoin daily for at least 6 months instead of a cumulative dose.^5,6 The relationship between change in lipids and total cumulative dose in our study may not be similar in patients treated with the dosing regimen recommended by the European guidelines, as our patients received a total cumulative dose instead of a daily low-dose isotretinoin regimen, unlike the European guidelines.⁵

Most liver transaminase abnormalities were detected in the second month. Abnormalities in GGT were seen in the second month and remained elevated at the next follow-up. However, clinically important grade 3 transaminase and GGT elevations were rare. It has been reported that GGT levels are more specific than transaminases in measuring hepatotoxicity.⁷ The fact that our patient with hepatotoxicity had a grade 3 GGT elevation in addition to grade 3 transaminase elevations supports that GGT elevation is more specific than transaminase levels in measuring hepatotoxicity. When these parameters were rechecked in our patients with grade 3 transaminase elevations, except in the case of hepatotoxicity, transaminase elevations did not recur, and GGT elevations did not accompany elevated transaminases, which suggested that transaminases may be elevated due to an extrahepatic origin (eg, hemolysis, exercise).

Rhabdomyolysis secondary to isotretinoin is rare in the literature of acne studies. In addition to clinical findings such as myalgia and fatigue, increased CK and abnormal liver enzymes, specifically AST, suggest the development of rhabdomyolysis.⁸ Our patient who developed rhabdomyolysis also had a recent history of vigorous exercise, grade 4 CK, and AST elevations. Other patients with isolated grade 3 CK elevations were informed about possible clinical signs of rhabdomyolysis, and they were able to complete their courses without any incident. According to a study by Landau et al,⁹ isotretinoin-associated hyperCKemia has been reported as benign. Similarly, our study found that isolated CK elevation during isotretinoin treatment may be misleading as a sign of rhabdomyolysis. Instead, CK monitoring may be more appropriate and cost-effective in patients with suspected clinical signs of rhabdomyolysis or in those with major elevations in transaminases, especially AST.

Conclusion

According to our study, hyperlipidemia was the most common complication in acne patients using isotretinoin. It may be appropriate to monitor the TG level at 2-month intervals in patients with grade 1 or 2 TG elevation at baseline to detect the possible risk for developing grade 3 hyperlipidemia. Periodic monitoring of LDL-C and TG levels may be appropriate, especially in patients who require a high total cumulative dose of isotretinoin. Clinically important liver enzyme abnormalities were rare in our study. Our findings support the idea that routine monthly monitoring of normal laboratory parameters is unnecessary and wasteful. Additionally, periodic monitoring of abnormal laboratory parameters should be considered on an individual basis.

Isotretinoin is used in the treatment of nodulocystic and severe papulopustular acne. During the treatment period, laboratory monitoring is recommended to identify the risk for complications such as hepatotoxicity, teratogenicity, rhabdomyolysis, hyperlipidemia, and pancreatitis.¹ There is a lack of consensus of the frequency of follow-up of laboratory parameters during isotretinoin treatment. This study evaluated the changes in laboratory parameters used in daily practice for patients with acne who were treated with isotretinoin to determine the optimum test repetition frequency.

Materials and Methods

We conducted a retrospective study of data from patients who received oral isotretinoin therapy for acne between January 2021 and July 2022 via the electronic medical records at Konya Numune Hospital and Konya Private Medova Hospital (both in Konya, Turkey). Patients who received an oral isotretinoin total cumulative dose greater than 120 mg/kg were included in the study. Patient demographic data; cumulative isotretinoin doses; and alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), creatinine kinase (CK), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels during treatment were recorded. Baseline laboratory levels of those parameters were compared with levels of the same parameters from the second and fourth months of treatment. Comparisons for all parameters were made between the second- and fourth-month levels. Reference ranges are shown in Table 1. Abnormalities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading system.² This study was approved by the Karatay University (Konya, Turkey) ethical committee.

Statistical Analysis—The descriptive statistics of the measurements were presented as means, standard deviations, or medians (first and third quartiles). With respect to the normal distribution, the consistency of the measurements was evaluated with the Kolmogorov-Smirnov test, and small deviations from the normal distribution were observed. Changes in laboratory measurements were evaluated with simple repeated-measures analysis of variance, and changes that differed significantly were determined by a Holm-Sidak post hoc test. Relationships between total cumulative doses and laboratory measurements at second visits were evaluated by the Pearson correlation analysis. The statistical significance level was P<.05. SPSS Statistics 23 (IBM) was used in the calculations.

Results

Consecutive Data at Baseline and Follow-up—A total of 415 patients with a mean age (SD) of 21.49 (7.25) years (range, 12–53 years) were included in our study. The mean total cumulative dose (SD) of the patients was 7267.27 (1878.4) mg. The consecutive data of the means of the laboratory parameters are shown in Table 1 and Figure 1. There was no significant change in the ALT levels between baseline and the fourth month as well as between the second- and fourth-month assessments (both P=.311). When comparing the differences among AST, GGT, and LDL-C measurements, the levels increased significantly between baseline and the second month and between baseline and the fourth month (all P<.001). There was no significant difference in CK levels at all assessments (all P=.304). When the differences between TG measurements were compared, the changes between baseline and the second month (P<.001), baseline and the fourth month (P<.001), and the second and fourth months (P=.013) were significant (Figure 1).

Abnormal Laboratory Measurements—The distribution of abnormal laboratory measurements during treatment is shown in Table 2 and Figure 2. Grade 3 or higher elevations of liver transaminases (ALT, AST) and GGT were observed in fewer than 2% of patients during treatment compared with baseline (grade 3 elevations of ALT and AST together in 2 patients; grade 4 AST elevation in 1 patient; grade 3 elevations of ALT, AST, and GGT combined in 1 patient; isolated grade 3 GGT elevation in 1 patient). All of the patients who developed grade 3 liver transaminases and isolated grade 3 GGT elevation had improved values when these were rechecked within 2 weeks.

In the patient who developed hepatotoxicity in the second month, the ALT level rose from a baseline of 19 U/L to 169 U/L, the AST level from a baseline of 19 U/L to 61 U/L, and the GGT level from a baseline of 24 U/L to 124 U/L. The patient was asymptomatic. Liver function test levels returned to reference range 4 weeks after discontinuation of therapy. Hepatotoxicity did not recur after treatment was re-administered.

The patient who developed grade 4 AST elevation (364 U/L) experienced fatigue and myalgia. He had done vigorous exercise up to 2 days before the test and also had a grade 4 CK elevation (12,310 U/L). He was thought to have isotretinoin-related rhabdomyolysis. His treatment was discontinued, and he was advised to hydrate and rest. Treatment was re-started after 2 weeks. With frequent laboratory monitoring and avoidance of vigorous physical activity, the patient completed the remaining course of isotretinoin without any laboratory abnormalities or symptoms.

Creatinine kinase abnormalities in the second and fourth months compared with baseline were not statistically significant. The patients with grade 3 or higher CK elevations, except for the case with rhabdomyolysis, had no clinical signs or other characteristic laboratory findings of rhabdomyolysis.

Hypercholesterolemia (LDL-C ≥130 mg/dL) occurred most frequently, with a maximum of 280 mg/dL in 1 patient (in the fourth month) and less than 250 mg/dL in all other patients. Hypercholesterolemia occurred in 183 (44.1%) patients in the second month and in 166 (40.0%) patients in the fourth month. However, baseline abnormalities also were frequent (86 [20.7%]), and hypercholesterolemia persisted in the second and fourth months in all of these patients.

It was observed that the patients with TG abnormalities increased continuously in the second (99 [23.9%]) and fourth (113 [27.2%]) months compared with baseline (49 [11.8%]). Grade 3 TG elevations were observed in 2.2% of patients (n=9; 5 patients in the second month, 4 patients in the fourth month) during treatment compared with baseline, and all patients had grade 1 or 2 hypertriglyceridemia at baseline. Of the patients with grade 3 TG elevation, 3 patients in the second month and 2 patients in the fourth month were obese at baseline. No grade 4 TG elevations were observed. Complications related to hyperlipidemia, such as pancreatitis, were observed in 1 patient. No patient terminated treatment because of lipid abnormalities. The treatment of our patients with major hypercholesterolemia and/or grade 3 hypertriglyceridemia was interrupted. The hyperlipidemia of these patients was controlled by a low-fat diet and a short-term dose reduction.

Relationship Between Total Cumulative Dose and Laboratory Parameters—The relationships between the total cumulative dose and changes up to the fourth month are presented in Table 3. As the total dose increased, the changes in TG and LDL-C levels significantly increased in the fourth month (both P=.001). However, the degree of these relationships was weak. No significant correlation was found between the periodic changes of other laboratory parameters and the total dose.

Comment

The parameters followed in our study show that TG levels tend to increase continuously from baseline during isotretinoin treatment, while ALT, AST, GGT, and LDL-C levels increase in the second month and decrease at 4 months. Although this same trend occurs with CK levels, the change was not statistically significant. The most common laboratory abnormality in our study was hyperlipidemia. Levels of LDL-C and TG were both found to be statistically elevated in the second and fourth months of treatment compared with baseline. Parthasarathy et al³ reported that obesity had an important role in the increase of lipid levels in patients using isotretinoin at baseline. In our study, 5 of 9 patients (55.6%) with grade 3 TG elevation were obese, which supports the theory that obesity plays an important role in the increase in lipid levels. Up-to-date laboratory follow-up of lipids suggests that there is no need to follow up serum lipids after the second month of treatment. Patients with risk factors for hyperlipidemia, such as abdominal obesity and familial hyperlipidemia, do not require further follow-up if there is no increase in serum lipids in the first month of treatment.¹ The presence of grade 1 or 2 hypertriglyceridemia at baseline in all our patients with grade 3 TG elevation may suggest that periodic laboratory follow-up during isotretinoin treatment is necessary to detect patients with grade 3 and higher TG levels.

The lack of knowledge of other risk factors (eg, familial hyperlipidemia, insulin resistance) for hyperlipidemia in all patients at baseline may be a limitation of our study. Although hypercholesterolemia persisted in the follow-up of our patients with initial LDL-C abnormalities, hypercholesterolemia over 250 mg/dL was very rare (1 patient). Possible complications associated with serum lipid abnormalities are pancreatitis and metabolic syndrome.⁴ In our study, none of the patients with lipid abnormalities had any relevant clinical sequelae. The dose-dependent elevation of the changes in LDL-C and TG (Table 3) may be important to predict the significant elevation of lipids and the associated complications in patients with a high total cumulative dose target that may require a long treatment duration. However, considering the short follow-up periods in our patients, the absence of clinical sequelae may be misleading. There are differences in recommendations between the US and European guidelines for isotretinoin dosage. Although the US guidelines recommend a total cumulative dose target, the European guidelines recommend low-dose isotretinoin daily for at least 6 months instead of a cumulative dose.^5,6 The relationship between change in lipids and total cumulative dose in our study may not be similar in patients treated with the dosing regimen recommended by the European guidelines, as our patients received a total cumulative dose instead of a daily low-dose isotretinoin regimen, unlike the European guidelines.⁵

Most liver transaminase abnormalities were detected in the second month. Abnormalities in GGT were seen in the second month and remained elevated at the next follow-up. However, clinically important grade 3 transaminase and GGT elevations were rare. It has been reported that GGT levels are more specific than transaminases in measuring hepatotoxicity.⁷ The fact that our patient with hepatotoxicity had a grade 3 GGT elevation in addition to grade 3 transaminase elevations supports that GGT elevation is more specific than transaminase levels in measuring hepatotoxicity. When these parameters were rechecked in our patients with grade 3 transaminase elevations, except in the case of hepatotoxicity, transaminase elevations did not recur, and GGT elevations did not accompany elevated transaminases, which suggested that transaminases may be elevated due to an extrahepatic origin (eg, hemolysis, exercise).

Rhabdomyolysis secondary to isotretinoin is rare in the literature of acne studies. In addition to clinical findings such as myalgia and fatigue, increased CK and abnormal liver enzymes, specifically AST, suggest the development of rhabdomyolysis.⁸ Our patient who developed rhabdomyolysis also had a recent history of vigorous exercise, grade 4 CK, and AST elevations. Other patients with isolated grade 3 CK elevations were informed about possible clinical signs of rhabdomyolysis, and they were able to complete their courses without any incident. According to a study by Landau et al,⁹ isotretinoin-associated hyperCKemia has been reported as benign. Similarly, our study found that isolated CK elevation during isotretinoin treatment may be misleading as a sign of rhabdomyolysis. Instead, CK monitoring may be more appropriate and cost-effective in patients with suspected clinical signs of rhabdomyolysis or in those with major elevations in transaminases, especially AST.

Conclusion

According to our study, hyperlipidemia was the most common complication in acne patients using isotretinoin. It may be appropriate to monitor the TG level at 2-month intervals in patients with grade 1 or 2 TG elevation at baseline to detect the possible risk for developing grade 3 hyperlipidemia. Periodic monitoring of LDL-C and TG levels may be appropriate, especially in patients who require a high total cumulative dose of isotretinoin. Clinically important liver enzyme abnormalities were rare in our study. Our findings support the idea that routine monthly monitoring of normal laboratory parameters is unnecessary and wasteful. Additionally, periodic monitoring of abnormal laboratory parameters should be considered on an individual basis.

Isotretinoin is used in the treatment of nodulocystic and severe papulopustular acne. During the treatment period, laboratory monitoring is recommended to identify the risk for complications such as hepatotoxicity, teratogenicity, rhabdomyolysis, hyperlipidemia, and pancreatitis.¹ There is a lack of consensus of the frequency of follow-up of laboratory parameters during isotretinoin treatment. This study evaluated the changes in laboratory parameters used in daily practice for patients with acne who were treated with isotretinoin to determine the optimum test repetition frequency.

Materials and Methods

We conducted a retrospective study of data from patients who received oral isotretinoin therapy for acne between January 2021 and July 2022 via the electronic medical records at Konya Numune Hospital and Konya Private Medova Hospital (both in Konya, Turkey). Patients who received an oral isotretinoin total cumulative dose greater than 120 mg/kg were included in the study. Patient demographic data; cumulative isotretinoin doses; and alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), creatinine kinase (CK), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels during treatment were recorded. Baseline laboratory levels of those parameters were compared with levels of the same parameters from the second and fourth months of treatment. Comparisons for all parameters were made between the second- and fourth-month levels. Reference ranges are shown in Table 1. Abnormalities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading system.² This study was approved by the Karatay University (Konya, Turkey) ethical committee.

Statistical Analysis—The descriptive statistics of the measurements were presented as means, standard deviations, or medians (first and third quartiles). With respect to the normal distribution, the consistency of the measurements was evaluated with the Kolmogorov-Smirnov test, and small deviations from the normal distribution were observed. Changes in laboratory measurements were evaluated with simple repeated-measures analysis of variance, and changes that differed significantly were determined by a Holm-Sidak post hoc test. Relationships between total cumulative doses and laboratory measurements at second visits were evaluated by the Pearson correlation analysis. The statistical significance level was P<.05. SPSS Statistics 23 (IBM) was used in the calculations.

Results

Consecutive Data at Baseline and Follow-up—A total of 415 patients with a mean age (SD) of 21.49 (7.25) years (range, 12–53 years) were included in our study. The mean total cumulative dose (SD) of the patients was 7267.27 (1878.4) mg. The consecutive data of the means of the laboratory parameters are shown in Table 1 and Figure 1. There was no significant change in the ALT levels between baseline and the fourth month as well as between the second- and fourth-month assessments (both P=.311). When comparing the differences among AST, GGT, and LDL-C measurements, the levels increased significantly between baseline and the second month and between baseline and the fourth month (all P<.001). There was no significant difference in CK levels at all assessments (all P=.304). When the differences between TG measurements were compared, the changes between baseline and the second month (P<.001), baseline and the fourth month (P<.001), and the second and fourth months (P=.013) were significant (Figure 1).

Abnormal Laboratory Measurements—The distribution of abnormal laboratory measurements during treatment is shown in Table 2 and Figure 2. Grade 3 or higher elevations of liver transaminases (ALT, AST) and GGT were observed in fewer than 2% of patients during treatment compared with baseline (grade 3 elevations of ALT and AST together in 2 patients; grade 4 AST elevation in 1 patient; grade 3 elevations of ALT, AST, and GGT combined in 1 patient; isolated grade 3 GGT elevation in 1 patient). All of the patients who developed grade 3 liver transaminases and isolated grade 3 GGT elevation had improved values when these were rechecked within 2 weeks.

In the patient who developed hepatotoxicity in the second month, the ALT level rose from a baseline of 19 U/L to 169 U/L, the AST level from a baseline of 19 U/L to 61 U/L, and the GGT level from a baseline of 24 U/L to 124 U/L. The patient was asymptomatic. Liver function test levels returned to reference range 4 weeks after discontinuation of therapy. Hepatotoxicity did not recur after treatment was re-administered.

The patient who developed grade 4 AST elevation (364 U/L) experienced fatigue and myalgia. He had done vigorous exercise up to 2 days before the test and also had a grade 4 CK elevation (12,310 U/L). He was thought to have isotretinoin-related rhabdomyolysis. His treatment was discontinued, and he was advised to hydrate and rest. Treatment was re-started after 2 weeks. With frequent laboratory monitoring and avoidance of vigorous physical activity, the patient completed the remaining course of isotretinoin without any laboratory abnormalities or symptoms.

Creatinine kinase abnormalities in the second and fourth months compared with baseline were not statistically significant. The patients with grade 3 or higher CK elevations, except for the case with rhabdomyolysis, had no clinical signs or other characteristic laboratory findings of rhabdomyolysis.

Hypercholesterolemia (LDL-C ≥130 mg/dL) occurred most frequently, with a maximum of 280 mg/dL in 1 patient (in the fourth month) and less than 250 mg/dL in all other patients. Hypercholesterolemia occurred in 183 (44.1%) patients in the second month and in 166 (40.0%) patients in the fourth month. However, baseline abnormalities also were frequent (86 [20.7%]), and hypercholesterolemia persisted in the second and fourth months in all of these patients.

It was observed that the patients with TG abnormalities increased continuously in the second (99 [23.9%]) and fourth (113 [27.2%]) months compared with baseline (49 [11.8%]). Grade 3 TG elevations were observed in 2.2% of patients (n=9; 5 patients in the second month, 4 patients in the fourth month) during treatment compared with baseline, and all patients had grade 1 or 2 hypertriglyceridemia at baseline. Of the patients with grade 3 TG elevation, 3 patients in the second month and 2 patients in the fourth month were obese at baseline. No grade 4 TG elevations were observed. Complications related to hyperlipidemia, such as pancreatitis, were observed in 1 patient. No patient terminated treatment because of lipid abnormalities. The treatment of our patients with major hypercholesterolemia and/or grade 3 hypertriglyceridemia was interrupted. The hyperlipidemia of these patients was controlled by a low-fat diet and a short-term dose reduction.

Relationship Between Total Cumulative Dose and Laboratory Parameters—The relationships between the total cumulative dose and changes up to the fourth month are presented in Table 3. As the total dose increased, the changes in TG and LDL-C levels significantly increased in the fourth month (both P=.001). However, the degree of these relationships was weak. No significant correlation was found between the periodic changes of other laboratory parameters and the total dose.

Comment

The parameters followed in our study show that TG levels tend to increase continuously from baseline during isotretinoin treatment, while ALT, AST, GGT, and LDL-C levels increase in the second month and decrease at 4 months. Although this same trend occurs with CK levels, the change was not statistically significant. The most common laboratory abnormality in our study was hyperlipidemia. Levels of LDL-C and TG were both found to be statistically elevated in the second and fourth months of treatment compared with baseline. Parthasarathy et al³ reported that obesity had an important role in the increase of lipid levels in patients using isotretinoin at baseline. In our study, 5 of 9 patients (55.6%) with grade 3 TG elevation were obese, which supports the theory that obesity plays an important role in the increase in lipid levels. Up-to-date laboratory follow-up of lipids suggests that there is no need to follow up serum lipids after the second month of treatment. Patients with risk factors for hyperlipidemia, such as abdominal obesity and familial hyperlipidemia, do not require further follow-up if there is no increase in serum lipids in the first month of treatment.¹ The presence of grade 1 or 2 hypertriglyceridemia at baseline in all our patients with grade 3 TG elevation may suggest that periodic laboratory follow-up during isotretinoin treatment is necessary to detect patients with grade 3 and higher TG levels.

The lack of knowledge of other risk factors (eg, familial hyperlipidemia, insulin resistance) for hyperlipidemia in all patients at baseline may be a limitation of our study. Although hypercholesterolemia persisted in the follow-up of our patients with initial LDL-C abnormalities, hypercholesterolemia over 250 mg/dL was very rare (1 patient). Possible complications associated with serum lipid abnormalities are pancreatitis and metabolic syndrome.⁴ In our study, none of the patients with lipid abnormalities had any relevant clinical sequelae. The dose-dependent elevation of the changes in LDL-C and TG (Table 3) may be important to predict the significant elevation of lipids and the associated complications in patients with a high total cumulative dose target that may require a long treatment duration. However, considering the short follow-up periods in our patients, the absence of clinical sequelae may be misleading. There are differences in recommendations between the US and European guidelines for isotretinoin dosage. Although the US guidelines recommend a total cumulative dose target, the European guidelines recommend low-dose isotretinoin daily for at least 6 months instead of a cumulative dose.^5,6 The relationship between change in lipids and total cumulative dose in our study may not be similar in patients treated with the dosing regimen recommended by the European guidelines, as our patients received a total cumulative dose instead of a daily low-dose isotretinoin regimen, unlike the European guidelines.⁵

Most liver transaminase abnormalities were detected in the second month. Abnormalities in GGT were seen in the second month and remained elevated at the next follow-up. However, clinically important grade 3 transaminase and GGT elevations were rare. It has been reported that GGT levels are more specific than transaminases in measuring hepatotoxicity.⁷ The fact that our patient with hepatotoxicity had a grade 3 GGT elevation in addition to grade 3 transaminase elevations supports that GGT elevation is more specific than transaminase levels in measuring hepatotoxicity. When these parameters were rechecked in our patients with grade 3 transaminase elevations, except in the case of hepatotoxicity, transaminase elevations did not recur, and GGT elevations did not accompany elevated transaminases, which suggested that transaminases may be elevated due to an extrahepatic origin (eg, hemolysis, exercise).

Rhabdomyolysis secondary to isotretinoin is rare in the literature of acne studies. In addition to clinical findings such as myalgia and fatigue, increased CK and abnormal liver enzymes, specifically AST, suggest the development of rhabdomyolysis.⁸ Our patient who developed rhabdomyolysis also had a recent history of vigorous exercise, grade 4 CK, and AST elevations. Other patients with isolated grade 3 CK elevations were informed about possible clinical signs of rhabdomyolysis, and they were able to complete their courses without any incident. According to a study by Landau et al,⁹ isotretinoin-associated hyperCKemia has been reported as benign. Similarly, our study found that isolated CK elevation during isotretinoin treatment may be misleading as a sign of rhabdomyolysis. Instead, CK monitoring may be more appropriate and cost-effective in patients with suspected clinical signs of rhabdomyolysis or in those with major elevations in transaminases, especially AST.

Conclusion

According to our study, hyperlipidemia was the most common complication in acne patients using isotretinoin. It may be appropriate to monitor the TG level at 2-month intervals in patients with grade 1 or 2 TG elevation at baseline to detect the possible risk for developing grade 3 hyperlipidemia. Periodic monitoring of LDL-C and TG levels may be appropriate, especially in patients who require a high total cumulative dose of isotretinoin. Clinically important liver enzyme abnormalities were rare in our study. Our findings support the idea that routine monthly monitoring of normal laboratory parameters is unnecessary and wasteful. Additionally, periodic monitoring of abnormal laboratory parameters should be considered on an individual basis.

It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.¹ Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.^2-4

If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.⁵ Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.⁶ This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.^7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.^10-12

Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.¹³ This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.^14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.^17,18

I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.

Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.^19-21

There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.

It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.¹ Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.^2-4

If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.⁵ Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.⁶ This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.^7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.^10-12

Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.¹³ This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.^14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.^17,18

I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.

Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.^19-21

There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.

It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.¹ Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.^2-4

If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.⁵ Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.⁶ This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.^7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.^10-12

Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.¹³ This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.^14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.^17,18

I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.

Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.^19-21

There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.

Looking back on her career as a gastroenterologist, Mariam Naveed, MD, sees the gastroenterology fellowship program she created at AdventHealth in Orlando, Fla., as a pinnacle moment.

Her first faculty position as assistant program director for the gastroenterology fellowship program at the University of Iowa offered some inspiration. “I loved teaching and working with trainees and knew I always wanted to remain in this realm,” Dr. Naveed said.

When she moved to Orlando to join AdventHealth, she noticed there was no gastroenterology training program. “I was strictly in private practice. Though I love working with patients, I constantly felt like something was missing. When the opportunity to start a fellowship program came, I was highly motivated to bring it to fruition.”

The AdventHealth fellowship is almost done with its inaugural year.

“Starting a fellowship at a new institution is a very challenging yet incredibly rewarding experience,” she said. In this Q&A, she discusses her strategies for dealing with insurance companies and imposter syndrome, and why she looks to her father as her role model in medicine.
 

Q: Why did you choose GI?

Dr. Naveed: Gastroenterology is a rapidly evolving field which makes it incredibly fascinating. The initial draw was that I was always excited to learn about GI physiology and disease. I also was fortunate to train with amazing gastroenterologists during residency. I had great examples of strong and successful female GIs to look up to. Lastly, for the most part, gastroenterologists are all fairly laid back and have an interesting sense of humor.

Q: What gives you the most joy in your day-to-day practice?

Dr. Naveed: I love learning and teaching. As a program director, I am directly involved with fellows, residents, and students, but there are always additional enrichment opportunities beyond these interactions. I value teaching clinic medical assistants so they feel more confident and empowered in their work. I also try to educate my nurse practitioners. The best compliment at the end of a long day is that they learned something valuable.

Q: How do you stay current with advances in your field?

Dr. Naveed: Between my role as a physician and as an educator, I owe it to my patients and trainees to stay current with advances in the field. But of course, this is challenging, and at times it feels like there are not enough hours in the day. While reading journal articles and attending conferences are great ways to refresh one’s knowledge, the winner for me has been social media (specifically Twitter). It’s easy to find a “Tweetorial” on almost any topic. There are some excellent initiatives on Twitter such as Monday Night IBD, ACG Evidence-Based GI Doc, Scoping Sundays, and GI Journal Club where important articles, new treatment options, and challenging cases are discussed. Of course, I also learn a lot from my fellows and residents.

Q: What fears did you have to push past to get to where you are in your career?

Dr. Naveed: Pushing past imposter syndrome, which is a feeling of self-doubt despite education, experience, and accomplishments. It is something many of us deal with. I’ve had to retire the notion that I am not experienced enough to achieve a particular career goal.

Q: What habits have you established that have benefited your career most?

Dr. Naveed: It’s a challenge to not immediately say “yes” to every opportunity or project. It’s also difficult to learn to delegate. I am lucky to have a great team, and I have learned that delegating certain tasks or projects helps everyone grow. Also, if I say no to an opportunity, I still try to suggest another colleague or mentee who may be interested and/or a good fit.
 

Q: Describe your biggest practice-related challenge and what you are doing to address it.

Dr. Naveed: Pushback from insurance companies to approve medications or interventions is incredibly frustrating for myself and the patient. It is also incredibly time consuming and requires significant clinical bandwidth that could otherwise be used in other capacities. While not a solution, I at least try to make sure the patient is kept updated and understands causes of delay, and more importantly, what we are doing to address the issue. I have realized that it’s always preferable to empower the patient, rather than leave them uninformed, which can foster frustration and dissatisfaction.

Q: What teacher or mentor had the greatest impact on you?

Dr. Naveed: I have been blessed with many mentors at different points in my medical career that have greatly impacted and shaped my journey. During my fellowship at University of Texas Southwestern (UTSW), Nisa Kubiliun, MD, was not only a mentor, but also an incredible sponsor. She saw potential in me and encouraged involvement in activities critical for career advancement. Arjmand Mufti, MD, the former program director of the UTSW GI fellowship, is still always just a call away when I need advice regarding my GI fellowship program at AdventHealth. I also have mentors and sponsors within my own institution who invest time and energy into my success.

Q: Outside of teachers and mentors, who or what has had the strongest influence in your life?

Dr. Naveed: My father, who is also a physician, has had a profound influence on my personal and professional development. His own medical journey has been incredibly unique. He has practiced medicine internationally, trained and worked in a traditional academic setting, established a very successful private practice, and now has transitioned to running a hospital-based practice. He has seen it all (and he’s also a brilliant physician), and he is always able to talk me through any situation.

Q: What principles guide you?

Dr. Naveed: Treating my patients how I would want a physician to treat my family is central to my practice. Also, I try to approach any successes with gratitude, and likewise, be patient with inevitable failures. It can be challenging, but I try to find the lesson in every failed venture.

Q: What would you do differently if you had a chance?

Dr. Naveed: I have always had an interest in international medical missions but have yet to participate in one. I have previously passed on such opportunities, thinking it was not the right time, but in hindsight I wish I had taken the leap. I still hope to eventually accomplish this goal.

Q: Describe a scene of your vision for the future.

Dr. Naveed: I hope that our GI fellowship continues to flourish and attract exceptional faculty and candidates. I want to remain involved in graduate medical education, but I hope to continue to challenge myself and advance within this domain. Most importantly, I hope I can continue to balance my career aspirations with my personal goals. I want to continue to be present for my family and kids.

Q: Describe how you would spend a free Saturday afternoon.

Dr. Naveed: You can usually find me at the local farmer’s market with my husband and kids. Afterwards, we’re definitely going to get Chick-fil-A followed by ice cream.

Lightning round

If you weren’t a gastroenterologist, what would you be?
International event planner.

How many cups of coffee do you drink per day?
Usually three.

Favorite breakfast?
Eggs, corned beef hash, toast.

Texting or talking?
Texting always unless it’s Mom or Dad. They always get a call.

Place you most want to travel?
Japan.

Follow Dr. Naveed on Twitter at @MN_GIMD

Looking back on her career as a gastroenterologist, Mariam Naveed, MD, sees the gastroenterology fellowship program she created at AdventHealth in Orlando, Fla., as a pinnacle moment.

Her first faculty position as assistant program director for the gastroenterology fellowship program at the University of Iowa offered some inspiration. “I loved teaching and working with trainees and knew I always wanted to remain in this realm,” Dr. Naveed said.

When she moved to Orlando to join AdventHealth, she noticed there was no gastroenterology training program. “I was strictly in private practice. Though I love working with patients, I constantly felt like something was missing. When the opportunity to start a fellowship program came, I was highly motivated to bring it to fruition.”

The AdventHealth fellowship is almost done with its inaugural year.

“Starting a fellowship at a new institution is a very challenging yet incredibly rewarding experience,” she said. In this Q&A, she discusses her strategies for dealing with insurance companies and imposter syndrome, and why she looks to her father as her role model in medicine.
 

Q: Why did you choose GI?

Dr. Naveed: Gastroenterology is a rapidly evolving field which makes it incredibly fascinating. The initial draw was that I was always excited to learn about GI physiology and disease. I also was fortunate to train with amazing gastroenterologists during residency. I had great examples of strong and successful female GIs to look up to. Lastly, for the most part, gastroenterologists are all fairly laid back and have an interesting sense of humor.

Q: What gives you the most joy in your day-to-day practice?

Dr. Naveed: I love learning and teaching. As a program director, I am directly involved with fellows, residents, and students, but there are always additional enrichment opportunities beyond these interactions. I value teaching clinic medical assistants so they feel more confident and empowered in their work. I also try to educate my nurse practitioners. The best compliment at the end of a long day is that they learned something valuable.

Q: How do you stay current with advances in your field?

Dr. Naveed: Between my role as a physician and as an educator, I owe it to my patients and trainees to stay current with advances in the field. But of course, this is challenging, and at times it feels like there are not enough hours in the day. While reading journal articles and attending conferences are great ways to refresh one’s knowledge, the winner for me has been social media (specifically Twitter). It’s easy to find a “Tweetorial” on almost any topic. There are some excellent initiatives on Twitter such as Monday Night IBD, ACG Evidence-Based GI Doc, Scoping Sundays, and GI Journal Club where important articles, new treatment options, and challenging cases are discussed. Of course, I also learn a lot from my fellows and residents.

Q: What fears did you have to push past to get to where you are in your career?

Dr. Naveed: Pushing past imposter syndrome, which is a feeling of self-doubt despite education, experience, and accomplishments. It is something many of us deal with. I’ve had to retire the notion that I am not experienced enough to achieve a particular career goal.

Q: What habits have you established that have benefited your career most?

Dr. Naveed: It’s a challenge to not immediately say “yes” to every opportunity or project. It’s also difficult to learn to delegate. I am lucky to have a great team, and I have learned that delegating certain tasks or projects helps everyone grow. Also, if I say no to an opportunity, I still try to suggest another colleague or mentee who may be interested and/or a good fit.
 

Q: Describe your biggest practice-related challenge and what you are doing to address it.

Dr. Naveed: Pushback from insurance companies to approve medications or interventions is incredibly frustrating for myself and the patient. It is also incredibly time consuming and requires significant clinical bandwidth that could otherwise be used in other capacities. While not a solution, I at least try to make sure the patient is kept updated and understands causes of delay, and more importantly, what we are doing to address the issue. I have realized that it’s always preferable to empower the patient, rather than leave them uninformed, which can foster frustration and dissatisfaction.

Q: What teacher or mentor had the greatest impact on you?

Dr. Naveed: I have been blessed with many mentors at different points in my medical career that have greatly impacted and shaped my journey. During my fellowship at University of Texas Southwestern (UTSW), Nisa Kubiliun, MD, was not only a mentor, but also an incredible sponsor. She saw potential in me and encouraged involvement in activities critical for career advancement. Arjmand Mufti, MD, the former program director of the UTSW GI fellowship, is still always just a call away when I need advice regarding my GI fellowship program at AdventHealth. I also have mentors and sponsors within my own institution who invest time and energy into my success.

Q: Outside of teachers and mentors, who or what has had the strongest influence in your life?

Dr. Naveed: My father, who is also a physician, has had a profound influence on my personal and professional development. His own medical journey has been incredibly unique. He has practiced medicine internationally, trained and worked in a traditional academic setting, established a very successful private practice, and now has transitioned to running a hospital-based practice. He has seen it all (and he’s also a brilliant physician), and he is always able to talk me through any situation.

Q: What principles guide you?

Dr. Naveed: Treating my patients how I would want a physician to treat my family is central to my practice. Also, I try to approach any successes with gratitude, and likewise, be patient with inevitable failures. It can be challenging, but I try to find the lesson in every failed venture.

Q: What would you do differently if you had a chance?

Dr. Naveed: I have always had an interest in international medical missions but have yet to participate in one. I have previously passed on such opportunities, thinking it was not the right time, but in hindsight I wish I had taken the leap. I still hope to eventually accomplish this goal.

Q: Describe a scene of your vision for the future.

Dr. Naveed: I hope that our GI fellowship continues to flourish and attract exceptional faculty and candidates. I want to remain involved in graduate medical education, but I hope to continue to challenge myself and advance within this domain. Most importantly, I hope I can continue to balance my career aspirations with my personal goals. I want to continue to be present for my family and kids.

Q: Describe how you would spend a free Saturday afternoon.

Dr. Naveed: You can usually find me at the local farmer’s market with my husband and kids. Afterwards, we’re definitely going to get Chick-fil-A followed by ice cream.

Lightning round

If you weren’t a gastroenterologist, what would you be?
International event planner.

How many cups of coffee do you drink per day?
Usually three.

Favorite breakfast?
Eggs, corned beef hash, toast.

Texting or talking?
Texting always unless it’s Mom or Dad. They always get a call.

Place you most want to travel?
Japan.

Follow Dr. Naveed on Twitter at @MN_GIMD

Looking back on her career as a gastroenterologist, Mariam Naveed, MD, sees the gastroenterology fellowship program she created at AdventHealth in Orlando, Fla., as a pinnacle moment.

Her first faculty position as assistant program director for the gastroenterology fellowship program at the University of Iowa offered some inspiration. “I loved teaching and working with trainees and knew I always wanted to remain in this realm,” Dr. Naveed said.

When she moved to Orlando to join AdventHealth, she noticed there was no gastroenterology training program. “I was strictly in private practice. Though I love working with patients, I constantly felt like something was missing. When the opportunity to start a fellowship program came, I was highly motivated to bring it to fruition.”

The AdventHealth fellowship is almost done with its inaugural year.

“Starting a fellowship at a new institution is a very challenging yet incredibly rewarding experience,” she said. In this Q&A, she discusses her strategies for dealing with insurance companies and imposter syndrome, and why she looks to her father as her role model in medicine.
 

Q: Why did you choose GI?

Dr. Naveed: Gastroenterology is a rapidly evolving field which makes it incredibly fascinating. The initial draw was that I was always excited to learn about GI physiology and disease. I also was fortunate to train with amazing gastroenterologists during residency. I had great examples of strong and successful female GIs to look up to. Lastly, for the most part, gastroenterologists are all fairly laid back and have an interesting sense of humor.

Q: What gives you the most joy in your day-to-day practice?

Dr. Naveed: I love learning and teaching. As a program director, I am directly involved with fellows, residents, and students, but there are always additional enrichment opportunities beyond these interactions. I value teaching clinic medical assistants so they feel more confident and empowered in their work. I also try to educate my nurse practitioners. The best compliment at the end of a long day is that they learned something valuable.

Q: How do you stay current with advances in your field?

Dr. Naveed: Between my role as a physician and as an educator, I owe it to my patients and trainees to stay current with advances in the field. But of course, this is challenging, and at times it feels like there are not enough hours in the day. While reading journal articles and attending conferences are great ways to refresh one’s knowledge, the winner for me has been social media (specifically Twitter). It’s easy to find a “Tweetorial” on almost any topic. There are some excellent initiatives on Twitter such as Monday Night IBD, ACG Evidence-Based GI Doc, Scoping Sundays, and GI Journal Club where important articles, new treatment options, and challenging cases are discussed. Of course, I also learn a lot from my fellows and residents.

Q: What fears did you have to push past to get to where you are in your career?

Dr. Naveed: Pushing past imposter syndrome, which is a feeling of self-doubt despite education, experience, and accomplishments. It is something many of us deal with. I’ve had to retire the notion that I am not experienced enough to achieve a particular career goal.

Q: What habits have you established that have benefited your career most?

Dr. Naveed: It’s a challenge to not immediately say “yes” to every opportunity or project. It’s also difficult to learn to delegate. I am lucky to have a great team, and I have learned that delegating certain tasks or projects helps everyone grow. Also, if I say no to an opportunity, I still try to suggest another colleague or mentee who may be interested and/or a good fit.
 

Q: Describe your biggest practice-related challenge and what you are doing to address it.

Dr. Naveed: Pushback from insurance companies to approve medications or interventions is incredibly frustrating for myself and the patient. It is also incredibly time consuming and requires significant clinical bandwidth that could otherwise be used in other capacities. While not a solution, I at least try to make sure the patient is kept updated and understands causes of delay, and more importantly, what we are doing to address the issue. I have realized that it’s always preferable to empower the patient, rather than leave them uninformed, which can foster frustration and dissatisfaction.

Q: What teacher or mentor had the greatest impact on you?

Dr. Naveed: I have been blessed with many mentors at different points in my medical career that have greatly impacted and shaped my journey. During my fellowship at University of Texas Southwestern (UTSW), Nisa Kubiliun, MD, was not only a mentor, but also an incredible sponsor. She saw potential in me and encouraged involvement in activities critical for career advancement. Arjmand Mufti, MD, the former program director of the UTSW GI fellowship, is still always just a call away when I need advice regarding my GI fellowship program at AdventHealth. I also have mentors and sponsors within my own institution who invest time and energy into my success.

Q: Outside of teachers and mentors, who or what has had the strongest influence in your life?

Dr. Naveed: My father, who is also a physician, has had a profound influence on my personal and professional development. His own medical journey has been incredibly unique. He has practiced medicine internationally, trained and worked in a traditional academic setting, established a very successful private practice, and now has transitioned to running a hospital-based practice. He has seen it all (and he’s also a brilliant physician), and he is always able to talk me through any situation.

Q: What principles guide you?

Dr. Naveed: Treating my patients how I would want a physician to treat my family is central to my practice. Also, I try to approach any successes with gratitude, and likewise, be patient with inevitable failures. It can be challenging, but I try to find the lesson in every failed venture.

Q: What would you do differently if you had a chance?

Dr. Naveed: I have always had an interest in international medical missions but have yet to participate in one. I have previously passed on such opportunities, thinking it was not the right time, but in hindsight I wish I had taken the leap. I still hope to eventually accomplish this goal.

Q: Describe a scene of your vision for the future.

Dr. Naveed: I hope that our GI fellowship continues to flourish and attract exceptional faculty and candidates. I want to remain involved in graduate medical education, but I hope to continue to challenge myself and advance within this domain. Most importantly, I hope I can continue to balance my career aspirations with my personal goals. I want to continue to be present for my family and kids.

Q: Describe how you would spend a free Saturday afternoon.

Dr. Naveed: You can usually find me at the local farmer’s market with my husband and kids. Afterwards, we’re definitely going to get Chick-fil-A followed by ice cream.

Lightning round

If you weren’t a gastroenterologist, what would you be?
International event planner.

How many cups of coffee do you drink per day?
Usually three.

Favorite breakfast?
Eggs, corned beef hash, toast.

Texting or talking?
Texting always unless it’s Mom or Dad. They always get a call.

Place you most want to travel?
Japan.

Follow Dr. Naveed on Twitter at @MN_GIMD

CHICAGO – It has been an exciting time to be a hepatologist. During my career, I have witnessed some of the miracles in modern medicine. The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.

This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.

Michigan Medicine – University of Michigan

However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.

The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
 

Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

CHICAGO – It has been an exciting time to be a hepatologist. During my career, I have witnessed some of the miracles in modern medicine. The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.

This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.

Michigan Medicine – University of Michigan

However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.

The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
 

Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

CHICAGO – It has been an exciting time to be a hepatologist. During my career, I have witnessed some of the miracles in modern medicine. The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.

This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.

Michigan Medicine – University of Michigan

However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.

The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
 

Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.

For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.

In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.

For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.

In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.

For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.

In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief