MDedge Dermatology

Introduced in 1982, isotretinoin is a retinoid derivative that has been widely used to treat various dermatologic conditions such as acne vulgaris, rosacea, hidradenitis suppurativa, and hair folliculitis. ¹ It remains one of the most effective drugs for the treatment of all forms of acne vulgaris, especially the nodulocystic type, and exerts its effects via different mechanisms that affect the major domains involved in the pathogenesis of acne. ² One month after treatment initiation, isotretinoin suppresses sebum production by decreasing the size and activity of sebaceous glands. In addition, it notably stabilizes keratinization of the skin and decreases the number of Propionibacterium acnes, which will minimize the inflammation associated with acne. ^3,4 Despite its beneficial effects, isotretinoin therapy has been associated with several complications. The most commonly reported adverse effects include fissured lips, dry skin, eczema, epistaxis, dry eyes, gastrointestinal tract upset, angular stomatitis, and back pain. Less frequent systemic adverse effects have been reported and relate mainly to teratogenicity, pancreatitis, drug-induced hepatotoxicity, leukopenia, and thrombocytopenia. ⁵

Isotretinoin use has been associated with alterations in hepatic and lipid profiles; elevations of serum liver enzymes and triglycerides (TGs) following isotretinoin treatment have been reported.⁴ Consequently, different protocols for laboratory monitoring during isotretinoin therapy have been established and utilized by various health care institutes.⁶ Despite the time and economic investment involved, certain protocols recommend repetition of liver function tests and several other laboratory parameters following a baseline test.⁷ The aim of this study was to determine the prevalence of laboratory changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and TGs among patients with acne receiving isotretinoin therapy, as well as to link the initial and second laboratory readings of the aforementioned parameters following initiation of isotretinoin treatment.

Materials and Methods

This retrospective cohort design study obtained patient data, including laboratory test results, from the Electronic System for Integrated Health Information at King Khalid University Hospital (KKUH)(Riyadh, Saudi Arabia). All patients older than 16 years who presented with acne vulgaris to the dermatology department at KKUH; who received a course of isotretinoin for at least 4 weeks between 2011 and 2016; and who had available baseline readings of ALT, AST, cholesterol, and TGs, as well as 2 concurrent follow-up readings after isotretinoin treatment initiation, were included in this study. Patients with only 1 reading following treatment initiation and those receiving isotretinoin treatment for reasons other than acne were excluded. This study was approved by the institutional review board of the College of Medicine at King Saud University (Riyadh, Saudi Arabia)(E-18-3310).

Statistical Analysis
Data were entered into a Microsoft Excel document, and statistical analysis was performed using SPSS (version 22.0). Data were represented as numbers and percentages. Repeated measures analysis was performed using the Cochran Q test to compare proportions of abnormal laboratory values among 3 groups: baseline, first reading, and second reading. When test results were significant, a post hoc test was used to compare proportions between any 2 groups. Moreover, a Spearman rank correlation was performed to investigate the association between the daily isotretinoin dose and the laboratory parameters. Results with P<.05 were considered statistically significant.

Results

During the study period, treatment with oral isotretinoin was undertaken by 386 patients at KKUH. Several of these patients were excluded due to incomplete medical records. The age of the studied patients ranged from 17 to 60 years, with a median age of 24 years (interquartile range, 20−28 years). The daily administered dose ranged from 10 to 80 mg, with a median dose of 30 mg (interquartile range, 20−40 mg), as illustrated in the Table. Repeated-measures analysis of liver enzymes (AST and ALT), total cholesterol, and TGs is detailed in eTable 1. Eight (2.2%) of 371 patients showed abnormal baseline AST levels. The first follow-up measurements of AST revealed high levels in 7 (1.9%) patients. This figure doubled (14 [3.8%] patients) at the second follow-up, with no statistically significant differences (P>.05). Likewise, ALT showed abnormally high levels at baseline and at both the first and second follow-ups (47/371 [12.7%], 49/371 [13.2%], and 37/371 [10.0%], respectively) with no significant differences (P>.05). Furthermore, the proportions of high cholesterol levels at baseline and at both the first and second follow-ups (40/331 [12.1%], 72/331 [21.8%], and 62/331 [18.7%], respectively) showed a statistically significant difference (P=.001). The proportions of high cholesterol levels in both the first and second follow-ups were significantly higher than the baseline proportions (P=.001 and P=.002, respectively). However, the percentages of high cholesterol were reduced at the second reading relative to the first but with no significant differences. Regarding TGs, there was a statistically significant difference in the proportions of high levels over time (5/320 [1.6%], 12/320 [3.8%], and 14/320 [4.4%] at baseline and at the first and second readings, respectively). Moreover, pairwise comparison among the 3 readings revealed a significant difference between the second follow-up and the baseline levels (P=.048). eTable 2 demonstrates statistically significant positive weak associations between the daily administered isotretinoin dose and each of the cholesterol and TG levels, both at the first and second follow-up readings (P<.05).

Comment

Evaluation of the effects of isotretinoin on liver enzymes and lipids has suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT) and lipid profiles to various degrees.⁸ Furthermore, there are controversies regarding the routine laboratory monitoring of these patients. Some studies have reported severe alterations in serum liver transaminase and lipid levels, and they support the need for careful monitoring when treating patients with isotretinoin. However, other studies have reported that adverse effects are minimal, with no need for costly laboratory monitoring.⁹

Our study explored the profile of changes in liver aminotransferases (AST and ALT), cholesterol, and TGs in patients with acne who had been treated with oral isotretinoin. The cholesterol levels showed a nonprogressive increase, with a prevalence rate of 21.8% and 18.7% at the first and second follow-ups, respectively. Likewise, the frequency of high TG levels was 3.8% and 4.4%, respectively, with significant differences from the baseline levels (P=.041). However, liver enzymes were less affected by isotretinoin therapy than lipid profiles. Both AST and ALT showed nonsignificant minimal elevations during follow-up of the patients.

Similar to our findings, Zane et al⁶ at the University of California, San Francisco, studied 13,772 patients with acne who underwent oral isotretinoin therapy between 1995 and 2002. They reported a cumulative incidence of new abnormalities in patients with normal values at baseline at a frequency of 44% for TG levels, 31% for total cholesterol levels, and 11% for transaminase levels. Moreover, they suggested that these abnormalities generally were transient and reversible.⁶ Another retrospective study in Brazil included 130 patients who were treated with isotretinoin for 3 months and reported that TG levels had increased beyond the normal range in 11% of patients, whereas 8.6% had elevated AST levels and 7.3% had elevated ALT levels.⁸ Comparable to our findings, Kizilyel et al¹⁰ concluded that isotretinoin appeared to have a greater effect on lipids than on liver enzymes, and they recommended its use with careful monitoring.

The transient effects of isotretinoin therapy on lipid profiles were highlighted in an earlier study. It has been reported that the changes in low-density lipoprotein and TGs returned to baseline levels 2 months following termination of treatment.¹¹ Although many studies have reported alterations in serum transaminase and lipid levels, other studies fail to report any such effects. Alcalay et al⁷ investigated 907 patients who completed a treatment course lasting 5 to 9 months. They reported that only 1.5% of patients had serum TG levels above 400 mg. Additionally, serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of treatment. They concluded that isotretinoin is a safe therapeutic drug and suggested that there is no need for routine laboratory follow-up in young healthy patients apart from a pregnancy test for females.⁷ In addition, Brito et al¹² conducted a prospective clinical and laboratory evaluation of 150 patients being treated with oral isotretinoin prior to the start of therapy, 1 month after therapy initiation, and every 3 months thereafter until the completion of treatment. They found no statistically significant changes in liver transaminase, TG, or cholesterol levels.¹² In another study of 30 participants, Baxter et al¹³ also reported no significant changes in TG or cholesterol levels measured at baseline or during treatment with isotretinoin. Furthermore, a systematic review and meta-analysis has estimated the laboratory changes that occur during isotretinoin therapy of acne vulgaris.¹⁴ The evidence revealed in this study does not support monthly laboratory testing for use of standard doses of oral isotretinoin for the typical patient with acne.

Conclusion

In our study, liver enzymes were less affected than lipids in patients who were treated with isotretinoin. Additionally, laboratory alterations in lipid profiles were nonprogressive and nonsevere. Consequently, isotretinoin may be administered with minimal concern for changes in serum transaminase and lipid profile. However, physicians should exercise caution when administering isotretinoin in patients with a history of abnormal findings.

Introduced in 1982, isotretinoin is a retinoid derivative that has been widely used to treat various dermatologic conditions such as acne vulgaris, rosacea, hidradenitis suppurativa, and hair folliculitis. ¹ It remains one of the most effective drugs for the treatment of all forms of acne vulgaris, especially the nodulocystic type, and exerts its effects via different mechanisms that affect the major domains involved in the pathogenesis of acne. ² One month after treatment initiation, isotretinoin suppresses sebum production by decreasing the size and activity of sebaceous glands. In addition, it notably stabilizes keratinization of the skin and decreases the number of Propionibacterium acnes, which will minimize the inflammation associated with acne. ^3,4 Despite its beneficial effects, isotretinoin therapy has been associated with several complications. The most commonly reported adverse effects include fissured lips, dry skin, eczema, epistaxis, dry eyes, gastrointestinal tract upset, angular stomatitis, and back pain. Less frequent systemic adverse effects have been reported and relate mainly to teratogenicity, pancreatitis, drug-induced hepatotoxicity, leukopenia, and thrombocytopenia. ⁵

Isotretinoin use has been associated with alterations in hepatic and lipid profiles; elevations of serum liver enzymes and triglycerides (TGs) following isotretinoin treatment have been reported.⁴ Consequently, different protocols for laboratory monitoring during isotretinoin therapy have been established and utilized by various health care institutes.⁶ Despite the time and economic investment involved, certain protocols recommend repetition of liver function tests and several other laboratory parameters following a baseline test.⁷ The aim of this study was to determine the prevalence of laboratory changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and TGs among patients with acne receiving isotretinoin therapy, as well as to link the initial and second laboratory readings of the aforementioned parameters following initiation of isotretinoin treatment.

Materials and Methods

This retrospective cohort design study obtained patient data, including laboratory test results, from the Electronic System for Integrated Health Information at King Khalid University Hospital (KKUH)(Riyadh, Saudi Arabia). All patients older than 16 years who presented with acne vulgaris to the dermatology department at KKUH; who received a course of isotretinoin for at least 4 weeks between 2011 and 2016; and who had available baseline readings of ALT, AST, cholesterol, and TGs, as well as 2 concurrent follow-up readings after isotretinoin treatment initiation, were included in this study. Patients with only 1 reading following treatment initiation and those receiving isotretinoin treatment for reasons other than acne were excluded. This study was approved by the institutional review board of the College of Medicine at King Saud University (Riyadh, Saudi Arabia)(E-18-3310).

Statistical Analysis
Data were entered into a Microsoft Excel document, and statistical analysis was performed using SPSS (version 22.0). Data were represented as numbers and percentages. Repeated measures analysis was performed using the Cochran Q test to compare proportions of abnormal laboratory values among 3 groups: baseline, first reading, and second reading. When test results were significant, a post hoc test was used to compare proportions between any 2 groups. Moreover, a Spearman rank correlation was performed to investigate the association between the daily isotretinoin dose and the laboratory parameters. Results with P<.05 were considered statistically significant.

Results

During the study period, treatment with oral isotretinoin was undertaken by 386 patients at KKUH. Several of these patients were excluded due to incomplete medical records. The age of the studied patients ranged from 17 to 60 years, with a median age of 24 years (interquartile range, 20−28 years). The daily administered dose ranged from 10 to 80 mg, with a median dose of 30 mg (interquartile range, 20−40 mg), as illustrated in the Table. Repeated-measures analysis of liver enzymes (AST and ALT), total cholesterol, and TGs is detailed in eTable 1. Eight (2.2%) of 371 patients showed abnormal baseline AST levels. The first follow-up measurements of AST revealed high levels in 7 (1.9%) patients. This figure doubled (14 [3.8%] patients) at the second follow-up, with no statistically significant differences (P>.05). Likewise, ALT showed abnormally high levels at baseline and at both the first and second follow-ups (47/371 [12.7%], 49/371 [13.2%], and 37/371 [10.0%], respectively) with no significant differences (P>.05). Furthermore, the proportions of high cholesterol levels at baseline and at both the first and second follow-ups (40/331 [12.1%], 72/331 [21.8%], and 62/331 [18.7%], respectively) showed a statistically significant difference (P=.001). The proportions of high cholesterol levels in both the first and second follow-ups were significantly higher than the baseline proportions (P=.001 and P=.002, respectively). However, the percentages of high cholesterol were reduced at the second reading relative to the first but with no significant differences. Regarding TGs, there was a statistically significant difference in the proportions of high levels over time (5/320 [1.6%], 12/320 [3.8%], and 14/320 [4.4%] at baseline and at the first and second readings, respectively). Moreover, pairwise comparison among the 3 readings revealed a significant difference between the second follow-up and the baseline levels (P=.048). eTable 2 demonstrates statistically significant positive weak associations between the daily administered isotretinoin dose and each of the cholesterol and TG levels, both at the first and second follow-up readings (P<.05).

Comment

Evaluation of the effects of isotretinoin on liver enzymes and lipids has suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT) and lipid profiles to various degrees.⁸ Furthermore, there are controversies regarding the routine laboratory monitoring of these patients. Some studies have reported severe alterations in serum liver transaminase and lipid levels, and they support the need for careful monitoring when treating patients with isotretinoin. However, other studies have reported that adverse effects are minimal, with no need for costly laboratory monitoring.⁹

Our study explored the profile of changes in liver aminotransferases (AST and ALT), cholesterol, and TGs in patients with acne who had been treated with oral isotretinoin. The cholesterol levels showed a nonprogressive increase, with a prevalence rate of 21.8% and 18.7% at the first and second follow-ups, respectively. Likewise, the frequency of high TG levels was 3.8% and 4.4%, respectively, with significant differences from the baseline levels (P=.041). However, liver enzymes were less affected by isotretinoin therapy than lipid profiles. Both AST and ALT showed nonsignificant minimal elevations during follow-up of the patients.

Similar to our findings, Zane et al⁶ at the University of California, San Francisco, studied 13,772 patients with acne who underwent oral isotretinoin therapy between 1995 and 2002. They reported a cumulative incidence of new abnormalities in patients with normal values at baseline at a frequency of 44% for TG levels, 31% for total cholesterol levels, and 11% for transaminase levels. Moreover, they suggested that these abnormalities generally were transient and reversible.⁶ Another retrospective study in Brazil included 130 patients who were treated with isotretinoin for 3 months and reported that TG levels had increased beyond the normal range in 11% of patients, whereas 8.6% had elevated AST levels and 7.3% had elevated ALT levels.⁸ Comparable to our findings, Kizilyel et al¹⁰ concluded that isotretinoin appeared to have a greater effect on lipids than on liver enzymes, and they recommended its use with careful monitoring.

The transient effects of isotretinoin therapy on lipid profiles were highlighted in an earlier study. It has been reported that the changes in low-density lipoprotein and TGs returned to baseline levels 2 months following termination of treatment.¹¹ Although many studies have reported alterations in serum transaminase and lipid levels, other studies fail to report any such effects. Alcalay et al⁷ investigated 907 patients who completed a treatment course lasting 5 to 9 months. They reported that only 1.5% of patients had serum TG levels above 400 mg. Additionally, serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of treatment. They concluded that isotretinoin is a safe therapeutic drug and suggested that there is no need for routine laboratory follow-up in young healthy patients apart from a pregnancy test for females.⁷ In addition, Brito et al¹² conducted a prospective clinical and laboratory evaluation of 150 patients being treated with oral isotretinoin prior to the start of therapy, 1 month after therapy initiation, and every 3 months thereafter until the completion of treatment. They found no statistically significant changes in liver transaminase, TG, or cholesterol levels.¹² In another study of 30 participants, Baxter et al¹³ also reported no significant changes in TG or cholesterol levels measured at baseline or during treatment with isotretinoin. Furthermore, a systematic review and meta-analysis has estimated the laboratory changes that occur during isotretinoin therapy of acne vulgaris.¹⁴ The evidence revealed in this study does not support monthly laboratory testing for use of standard doses of oral isotretinoin for the typical patient with acne.

Conclusion

In our study, liver enzymes were less affected than lipids in patients who were treated with isotretinoin. Additionally, laboratory alterations in lipid profiles were nonprogressive and nonsevere. Consequently, isotretinoin may be administered with minimal concern for changes in serum transaminase and lipid profile. However, physicians should exercise caution when administering isotretinoin in patients with a history of abnormal findings.

Introduced in 1982, isotretinoin is a retinoid derivative that has been widely used to treat various dermatologic conditions such as acne vulgaris, rosacea, hidradenitis suppurativa, and hair folliculitis. ¹ It remains one of the most effective drugs for the treatment of all forms of acne vulgaris, especially the nodulocystic type, and exerts its effects via different mechanisms that affect the major domains involved in the pathogenesis of acne. ² One month after treatment initiation, isotretinoin suppresses sebum production by decreasing the size and activity of sebaceous glands. In addition, it notably stabilizes keratinization of the skin and decreases the number of Propionibacterium acnes, which will minimize the inflammation associated with acne. ^3,4 Despite its beneficial effects, isotretinoin therapy has been associated with several complications. The most commonly reported adverse effects include fissured lips, dry skin, eczema, epistaxis, dry eyes, gastrointestinal tract upset, angular stomatitis, and back pain. Less frequent systemic adverse effects have been reported and relate mainly to teratogenicity, pancreatitis, drug-induced hepatotoxicity, leukopenia, and thrombocytopenia. ⁵

Isotretinoin use has been associated with alterations in hepatic and lipid profiles; elevations of serum liver enzymes and triglycerides (TGs) following isotretinoin treatment have been reported.⁴ Consequently, different protocols for laboratory monitoring during isotretinoin therapy have been established and utilized by various health care institutes.⁶ Despite the time and economic investment involved, certain protocols recommend repetition of liver function tests and several other laboratory parameters following a baseline test.⁷ The aim of this study was to determine the prevalence of laboratory changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and TGs among patients with acne receiving isotretinoin therapy, as well as to link the initial and second laboratory readings of the aforementioned parameters following initiation of isotretinoin treatment.

Materials and Methods

This retrospective cohort design study obtained patient data, including laboratory test results, from the Electronic System for Integrated Health Information at King Khalid University Hospital (KKUH)(Riyadh, Saudi Arabia). All patients older than 16 years who presented with acne vulgaris to the dermatology department at KKUH; who received a course of isotretinoin for at least 4 weeks between 2011 and 2016; and who had available baseline readings of ALT, AST, cholesterol, and TGs, as well as 2 concurrent follow-up readings after isotretinoin treatment initiation, were included in this study. Patients with only 1 reading following treatment initiation and those receiving isotretinoin treatment for reasons other than acne were excluded. This study was approved by the institutional review board of the College of Medicine at King Saud University (Riyadh, Saudi Arabia)(E-18-3310).

Statistical Analysis
Data were entered into a Microsoft Excel document, and statistical analysis was performed using SPSS (version 22.0). Data were represented as numbers and percentages. Repeated measures analysis was performed using the Cochran Q test to compare proportions of abnormal laboratory values among 3 groups: baseline, first reading, and second reading. When test results were significant, a post hoc test was used to compare proportions between any 2 groups. Moreover, a Spearman rank correlation was performed to investigate the association between the daily isotretinoin dose and the laboratory parameters. Results with P<.05 were considered statistically significant.

Results

During the study period, treatment with oral isotretinoin was undertaken by 386 patients at KKUH. Several of these patients were excluded due to incomplete medical records. The age of the studied patients ranged from 17 to 60 years, with a median age of 24 years (interquartile range, 20−28 years). The daily administered dose ranged from 10 to 80 mg, with a median dose of 30 mg (interquartile range, 20−40 mg), as illustrated in the Table. Repeated-measures analysis of liver enzymes (AST and ALT), total cholesterol, and TGs is detailed in eTable 1. Eight (2.2%) of 371 patients showed abnormal baseline AST levels. The first follow-up measurements of AST revealed high levels in 7 (1.9%) patients. This figure doubled (14 [3.8%] patients) at the second follow-up, with no statistically significant differences (P>.05). Likewise, ALT showed abnormally high levels at baseline and at both the first and second follow-ups (47/371 [12.7%], 49/371 [13.2%], and 37/371 [10.0%], respectively) with no significant differences (P>.05). Furthermore, the proportions of high cholesterol levels at baseline and at both the first and second follow-ups (40/331 [12.1%], 72/331 [21.8%], and 62/331 [18.7%], respectively) showed a statistically significant difference (P=.001). The proportions of high cholesterol levels in both the first and second follow-ups were significantly higher than the baseline proportions (P=.001 and P=.002, respectively). However, the percentages of high cholesterol were reduced at the second reading relative to the first but with no significant differences. Regarding TGs, there was a statistically significant difference in the proportions of high levels over time (5/320 [1.6%], 12/320 [3.8%], and 14/320 [4.4%] at baseline and at the first and second readings, respectively). Moreover, pairwise comparison among the 3 readings revealed a significant difference between the second follow-up and the baseline levels (P=.048). eTable 2 demonstrates statistically significant positive weak associations between the daily administered isotretinoin dose and each of the cholesterol and TG levels, both at the first and second follow-up readings (P<.05).

Comment

Evaluation of the effects of isotretinoin on liver enzymes and lipids has suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT) and lipid profiles to various degrees.⁸ Furthermore, there are controversies regarding the routine laboratory monitoring of these patients. Some studies have reported severe alterations in serum liver transaminase and lipid levels, and they support the need for careful monitoring when treating patients with isotretinoin. However, other studies have reported that adverse effects are minimal, with no need for costly laboratory monitoring.⁹

Our study explored the profile of changes in liver aminotransferases (AST and ALT), cholesterol, and TGs in patients with acne who had been treated with oral isotretinoin. The cholesterol levels showed a nonprogressive increase, with a prevalence rate of 21.8% and 18.7% at the first and second follow-ups, respectively. Likewise, the frequency of high TG levels was 3.8% and 4.4%, respectively, with significant differences from the baseline levels (P=.041). However, liver enzymes were less affected by isotretinoin therapy than lipid profiles. Both AST and ALT showed nonsignificant minimal elevations during follow-up of the patients.

Similar to our findings, Zane et al⁶ at the University of California, San Francisco, studied 13,772 patients with acne who underwent oral isotretinoin therapy between 1995 and 2002. They reported a cumulative incidence of new abnormalities in patients with normal values at baseline at a frequency of 44% for TG levels, 31% for total cholesterol levels, and 11% for transaminase levels. Moreover, they suggested that these abnormalities generally were transient and reversible.⁶ Another retrospective study in Brazil included 130 patients who were treated with isotretinoin for 3 months and reported that TG levels had increased beyond the normal range in 11% of patients, whereas 8.6% had elevated AST levels and 7.3% had elevated ALT levels.⁸ Comparable to our findings, Kizilyel et al¹⁰ concluded that isotretinoin appeared to have a greater effect on lipids than on liver enzymes, and they recommended its use with careful monitoring.

The transient effects of isotretinoin therapy on lipid profiles were highlighted in an earlier study. It has been reported that the changes in low-density lipoprotein and TGs returned to baseline levels 2 months following termination of treatment.¹¹ Although many studies have reported alterations in serum transaminase and lipid levels, other studies fail to report any such effects. Alcalay et al⁷ investigated 907 patients who completed a treatment course lasting 5 to 9 months. They reported that only 1.5% of patients had serum TG levels above 400 mg. Additionally, serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of treatment. They concluded that isotretinoin is a safe therapeutic drug and suggested that there is no need for routine laboratory follow-up in young healthy patients apart from a pregnancy test for females.⁷ In addition, Brito et al¹² conducted a prospective clinical and laboratory evaluation of 150 patients being treated with oral isotretinoin prior to the start of therapy, 1 month after therapy initiation, and every 3 months thereafter until the completion of treatment. They found no statistically significant changes in liver transaminase, TG, or cholesterol levels.¹² In another study of 30 participants, Baxter et al¹³ also reported no significant changes in TG or cholesterol levels measured at baseline or during treatment with isotretinoin. Furthermore, a systematic review and meta-analysis has estimated the laboratory changes that occur during isotretinoin therapy of acne vulgaris.¹⁴ The evidence revealed in this study does not support monthly laboratory testing for use of standard doses of oral isotretinoin for the typical patient with acne.

Conclusion

In our study, liver enzymes were less affected than lipids in patients who were treated with isotretinoin. Additionally, laboratory alterations in lipid profiles were nonprogressive and nonsevere. Consequently, isotretinoin may be administered with minimal concern for changes in serum transaminase and lipid profile. However, physicians should exercise caution when administering isotretinoin in patients with a history of abnormal findings.

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Although adolescents with acne received different cumulative doses of isotretinoin based on their body mass index, there were no differences in acne clearance, relapse, and most side effects between normal-weight, overweight, and obese individuals, a retrospective cohort study found.

“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”

To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.

Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.

There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).

“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”

The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).

Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.

However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.

Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.

[email protected]

Although adolescents with acne received different cumulative doses of isotretinoin based on their body mass index, there were no differences in acne clearance, relapse, and most side effects between normal-weight, overweight, and obese individuals, a retrospective cohort study found.

“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”

To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.

Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.

There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).

“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”

The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).

Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.

However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.

Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.

[email protected]

Although adolescents with acne received different cumulative doses of isotretinoin based on their body mass index, there were no differences in acne clearance, relapse, and most side effects between normal-weight, overweight, and obese individuals, a retrospective cohort study found.

“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”

To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.

Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.

There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).

“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”

The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).

Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.

However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.

Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.

[email protected]

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.

Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”

Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.

Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.

This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.

Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.

The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
 

Unforgettable day

Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”

All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.

Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.

During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”

Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”

Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).

The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.

Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.

Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.

Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.

Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.

Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”

Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”

Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”

A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.

With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.

Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”

Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.

Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.

This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.

Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.

The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
 

Unforgettable day

Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”

All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.

Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.

During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”

Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”

Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).

The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.

Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.

Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.

Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.

Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.

Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”

Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”

Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”

A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.

With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.

Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”

Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.

Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.

This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.

Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.

The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
 

Unforgettable day

Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”

All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.

Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.

During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”

Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”

Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).

The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.

Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.

Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.

Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.

Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.

Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”

Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”

Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”

A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.

For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.

A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.

An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.

Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”

Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.

Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
 

Concerns about SLIT

One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.

On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.

But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).

Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.

Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”

Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.

But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.

Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”

On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”

Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.

SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.

As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.

One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.

A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.

For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.

A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.

An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.

Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”

Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.

Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
 

Concerns about SLIT

One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.

On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.

But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).

Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.

Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”

Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.

But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.

Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”

On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”

Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.

SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.

As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.

One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.

A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.

For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.

A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.

An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.

Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”

Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.

Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
 

Concerns about SLIT

One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.

On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.

But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).

Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.

Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”

Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.

But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.

Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”

On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”

Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.

SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.

As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.

One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.

A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.

In the last 5 years, both over-the-counter and professional use of glycolic acid has increased. Glycolic acid is available in creams, pads, lotions, and cleansers, and for compounding, in concentrations of 0.08% to 70%. The extent of exfoliation with any of the alpha hydroxy acids depends on the type of acid, its concentration, and the pH of the preparations. Glycolic acid inhibits tyrosinase and chelates calcium ion concentration between the cells in the epidermis, which results in exfoliation of the skin.

Over-the-counter glycolic acid is available in concentrations up to 30%, and in professional products up to 70%. Clinically, glycolic acid above a concentration of 30% causes local burning, erythema, and dryness.

However, overuse of glycolic acid among consumers has increased the incidence of skin reactions and hyperpigmentation. Professional-grade products containing up to 70% glycolic acid are widely available on the Internet and without proper guidelines on use and sun avoidance, adverse events and long term scarring are becoming prevalent.

The overuse of acids and overexfoliation of the skin in patients with skin types I-IV is a growing problem as consumers are purchasing more “at-home peels,” peel pads, glow pads, and at-home exfoliation regimens. This overexfoliation of the skin and the resulting erythema induces rapid postinflammatory hyperpigmentation. Consumers then often mistakenly try to self-treat the hyperpigmentation with increasing concentrations of acids, retinols, and/or hydroquinone on top of an already compromised skin barrier, further worsening the problem. In addition, these acids increase sensitivity to UV light and increase the risk of sunburns in all skin types.

Although glycolic acids are generally safe, standardized recommendations for their use in the skin care market are necessary. More is not always better. In our clinic, we do not treat patients with postinflammatory hyperpigmentation from acids or peels with more exfoliation. We focus on repairing the barrier for 1-3 months, which includes use of gentle cleansers and occlusive moisturizers, and avoidance of acids, retinols, or scrubs, and aggressive sun protection, and then using gentle fade ingredients – such as kojic acid, licorice root extract, and vitamin C – at low concentrations to slowly decrease melanin production. Barrier repair is the first and most important step and it is often overlooked when clinicians try to lighten the skin in haste.
 

Dr. Lily Talakoub and Dr. Naissan O. Wesley and are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. They had no relevant disclosures. Write to them at [email protected].

In the last 5 years, both over-the-counter and professional use of glycolic acid has increased. Glycolic acid is available in creams, pads, lotions, and cleansers, and for compounding, in concentrations of 0.08% to 70%. The extent of exfoliation with any of the alpha hydroxy acids depends on the type of acid, its concentration, and the pH of the preparations. Glycolic acid inhibits tyrosinase and chelates calcium ion concentration between the cells in the epidermis, which results in exfoliation of the skin.

Over-the-counter glycolic acid is available in concentrations up to 30%, and in professional products up to 70%. Clinically, glycolic acid above a concentration of 30% causes local burning, erythema, and dryness.

However, overuse of glycolic acid among consumers has increased the incidence of skin reactions and hyperpigmentation. Professional-grade products containing up to 70% glycolic acid are widely available on the Internet and without proper guidelines on use and sun avoidance, adverse events and long term scarring are becoming prevalent.

The overuse of acids and overexfoliation of the skin in patients with skin types I-IV is a growing problem as consumers are purchasing more “at-home peels,” peel pads, glow pads, and at-home exfoliation regimens. This overexfoliation of the skin and the resulting erythema induces rapid postinflammatory hyperpigmentation. Consumers then often mistakenly try to self-treat the hyperpigmentation with increasing concentrations of acids, retinols, and/or hydroquinone on top of an already compromised skin barrier, further worsening the problem. In addition, these acids increase sensitivity to UV light and increase the risk of sunburns in all skin types.

Although glycolic acids are generally safe, standardized recommendations for their use in the skin care market are necessary. More is not always better. In our clinic, we do not treat patients with postinflammatory hyperpigmentation from acids or peels with more exfoliation. We focus on repairing the barrier for 1-3 months, which includes use of gentle cleansers and occlusive moisturizers, and avoidance of acids, retinols, or scrubs, and aggressive sun protection, and then using gentle fade ingredients – such as kojic acid, licorice root extract, and vitamin C – at low concentrations to slowly decrease melanin production. Barrier repair is the first and most important step and it is often overlooked when clinicians try to lighten the skin in haste.
 

Dr. Lily Talakoub and Dr. Naissan O. Wesley and are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. They had no relevant disclosures. Write to them at [email protected].

In the last 5 years, both over-the-counter and professional use of glycolic acid has increased. Glycolic acid is available in creams, pads, lotions, and cleansers, and for compounding, in concentrations of 0.08% to 70%. The extent of exfoliation with any of the alpha hydroxy acids depends on the type of acid, its concentration, and the pH of the preparations. Glycolic acid inhibits tyrosinase and chelates calcium ion concentration between the cells in the epidermis, which results in exfoliation of the skin.

Over-the-counter glycolic acid is available in concentrations up to 30%, and in professional products up to 70%. Clinically, glycolic acid above a concentration of 30% causes local burning, erythema, and dryness.

However, overuse of glycolic acid among consumers has increased the incidence of skin reactions and hyperpigmentation. Professional-grade products containing up to 70% glycolic acid are widely available on the Internet and without proper guidelines on use and sun avoidance, adverse events and long term scarring are becoming prevalent.

The overuse of acids and overexfoliation of the skin in patients with skin types I-IV is a growing problem as consumers are purchasing more “at-home peels,” peel pads, glow pads, and at-home exfoliation regimens. This overexfoliation of the skin and the resulting erythema induces rapid postinflammatory hyperpigmentation. Consumers then often mistakenly try to self-treat the hyperpigmentation with increasing concentrations of acids, retinols, and/or hydroquinone on top of an already compromised skin barrier, further worsening the problem. In addition, these acids increase sensitivity to UV light and increase the risk of sunburns in all skin types.

Although glycolic acids are generally safe, standardized recommendations for their use in the skin care market are necessary. More is not always better. In our clinic, we do not treat patients with postinflammatory hyperpigmentation from acids or peels with more exfoliation. We focus on repairing the barrier for 1-3 months, which includes use of gentle cleansers and occlusive moisturizers, and avoidance of acids, retinols, or scrubs, and aggressive sun protection, and then using gentle fade ingredients – such as kojic acid, licorice root extract, and vitamin C – at low concentrations to slowly decrease melanin production. Barrier repair is the first and most important step and it is often overlooked when clinicians try to lighten the skin in haste.
 

Dr. Lily Talakoub and Dr. Naissan O. Wesley and are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. They had no relevant disclosures. Write to them at [email protected].

To the Editor:

Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.¹ Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al² describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.

A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).

The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al³ noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.

Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.⁴

Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.⁵ There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.

To the Editor:

Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.¹ Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al² describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.

A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).

The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al³ noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.

Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.⁴

Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.⁵ There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.

To the Editor:

Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.¹ Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al² describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.

A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).

The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al³ noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.

Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.⁴

Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.⁵ There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.

Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.

Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.

“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”

To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.

Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).

Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).

Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.

The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.

Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”

Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).

“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”

In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.

[email protected]

Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.

Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.

“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”

To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.

Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).

Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).

Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.

The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.

Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”

Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).

“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”

In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.

[email protected]

Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.

Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.

“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”

To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.

Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).

Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).

Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.

The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.

Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”

Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).

“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”

In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.

[email protected]