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More data back Guillain-Barré risk with Janssen COVID shot
Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9 to 12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.
Additionally, observed GBS cases after the Janssen shot were 2 to 3 times greater than expected, based on background rates within 21 and 42 days of vaccination.
Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.
The findings were published online in JAMA Network Open.
More precise risk estimates
Winston Abara, MD, with the U.S. Centers for Disease Control and Prevention, and colleagues analyzed GBS reports submitted to the VAERS between December 2020 and January 2022.
Among 487.6 million COVID-19 vaccine doses administered, 3.7% were Janssen’s Ad26.COV2.S vaccine, 54.7% were Pfizer’s BNT162b2 vaccine, and 41.6% were Moderna’s mRNA-1273 vaccine.
There were 295 verified reports of GBS identified after COVID-19 vaccination. Of these, 209 occurred within 21 days of vaccination and 253 within 42 days.
Within 21 days of vaccination, GBS reporting rates per 1 million doses were 3.29 for the Janssen vaccine versus 0.29 and 0.35 for the Pfizer and Moderna vaccines, respectively. Within 42 days of vaccination, reporting rates per 1 million doses were 4.07, 0.34, and 0.44, respectively.
Also within 21 days of vaccination, GBS reporting rates were significantly higher with the Janssen vaccine than the Pfizer vaccine (reporting rate ratio, 11.40) and the Moderna vaccine (RRR, 9.26). Similar findings were observed within 42 days after vaccination.
The observed-to-expected ratios were 3.79 for 21-day and 2.34 for 42-day intervals after receipt of the Janssen vaccine, and less than 1 (not significant) after the Pfizer or Moderna vaccine within both post-vaccination periods.
“Unlike prior studies, our analysis included all U.S. reports of verified GBS cases that met the Brighton Collaboration GBS case definition criteria (Brighton Levels 1, 2, and 3) submitted over a 14-month surveillance period to the to the Vaccine Adverse Event Reporting System,” Dr. Abara said in an interview. “Because we used all U.S. reports, the sample of verified GBS cases in this analysis is larger than other studies. Therefore, it may provide a more precise estimate of the GBS risk within 21 and 42 days after mRNA and Ad26.COV2.S vaccination,” he said.
‘Remarkably low’ use
Nicola Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Oakland, Calif., noted that this is a “nice confirmatory analysis that supports and further expands what’s been observed before.”
Last year, as reported by this news organization, Dr. Klein and colleagues reported data from the Vaccine Safety Datalink confirming a small but statistically significant increased risk for GBS in the 3 weeks after receipt of the Janssen COVID-19 vaccine but not the Pfizer or Moderna vaccines.
Unlike VAERS, the Vaccine Safety Datalink is not a reporting system. It’s an active surveillance of medical records in the Kaiser Permanente system. The VAERS is a passive system, so it requires individuals to report GBS cases to the VAERS team, Dr. Klein explained.
So although the two studies are slightly different, overall, the VAERS data is “consistent with what we found,” she said.
Also weighing in, C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and professor of pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn., said it is “important to realize that GBS had been observed after adenovirus-vectored vaccines earlier in the pandemic, both for the AstraZeneca vaccine and the Janssen vaccine.”
The Advisory Committee on Immunization Practices (ACIP) preferentially recommends that people age 18 years and older receive an mRNA COVID-19 vaccine rather than the Janssen adenoviral vector vaccine when both types of COVID-19 vaccine are available.
“Thus, the use of the Janssen vaccine is remarkably low in the U.S. right now,” Dr. Creech said.
“Nevertheless, we have a firm commitment, both scientifically and ethically, to track potential side effects after vaccination and to make sure that the vaccines in use for COVID, and other important infectious diseases, are safe and effective,” he added.
The study had no commercial funding. Dr. Abara and Dr. Creech have reported no relevant financial relationships. Dr. Klein reported having received grants from Pfizer research support for a COVID vaccine clinical trial, as well as grants from Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur).
A version of this article first appeared on Medscape.com.
Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9 to 12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.
Additionally, observed GBS cases after the Janssen shot were 2 to 3 times greater than expected, based on background rates within 21 and 42 days of vaccination.
Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.
The findings were published online in JAMA Network Open.
More precise risk estimates
Winston Abara, MD, with the U.S. Centers for Disease Control and Prevention, and colleagues analyzed GBS reports submitted to the VAERS between December 2020 and January 2022.
Among 487.6 million COVID-19 vaccine doses administered, 3.7% were Janssen’s Ad26.COV2.S vaccine, 54.7% were Pfizer’s BNT162b2 vaccine, and 41.6% were Moderna’s mRNA-1273 vaccine.
There were 295 verified reports of GBS identified after COVID-19 vaccination. Of these, 209 occurred within 21 days of vaccination and 253 within 42 days.
Within 21 days of vaccination, GBS reporting rates per 1 million doses were 3.29 for the Janssen vaccine versus 0.29 and 0.35 for the Pfizer and Moderna vaccines, respectively. Within 42 days of vaccination, reporting rates per 1 million doses were 4.07, 0.34, and 0.44, respectively.
Also within 21 days of vaccination, GBS reporting rates were significantly higher with the Janssen vaccine than the Pfizer vaccine (reporting rate ratio, 11.40) and the Moderna vaccine (RRR, 9.26). Similar findings were observed within 42 days after vaccination.
The observed-to-expected ratios were 3.79 for 21-day and 2.34 for 42-day intervals after receipt of the Janssen vaccine, and less than 1 (not significant) after the Pfizer or Moderna vaccine within both post-vaccination periods.
“Unlike prior studies, our analysis included all U.S. reports of verified GBS cases that met the Brighton Collaboration GBS case definition criteria (Brighton Levels 1, 2, and 3) submitted over a 14-month surveillance period to the to the Vaccine Adverse Event Reporting System,” Dr. Abara said in an interview. “Because we used all U.S. reports, the sample of verified GBS cases in this analysis is larger than other studies. Therefore, it may provide a more precise estimate of the GBS risk within 21 and 42 days after mRNA and Ad26.COV2.S vaccination,” he said.
‘Remarkably low’ use
Nicola Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Oakland, Calif., noted that this is a “nice confirmatory analysis that supports and further expands what’s been observed before.”
Last year, as reported by this news organization, Dr. Klein and colleagues reported data from the Vaccine Safety Datalink confirming a small but statistically significant increased risk for GBS in the 3 weeks after receipt of the Janssen COVID-19 vaccine but not the Pfizer or Moderna vaccines.
Unlike VAERS, the Vaccine Safety Datalink is not a reporting system. It’s an active surveillance of medical records in the Kaiser Permanente system. The VAERS is a passive system, so it requires individuals to report GBS cases to the VAERS team, Dr. Klein explained.
So although the two studies are slightly different, overall, the VAERS data is “consistent with what we found,” she said.
Also weighing in, C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and professor of pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn., said it is “important to realize that GBS had been observed after adenovirus-vectored vaccines earlier in the pandemic, both for the AstraZeneca vaccine and the Janssen vaccine.”
The Advisory Committee on Immunization Practices (ACIP) preferentially recommends that people age 18 years and older receive an mRNA COVID-19 vaccine rather than the Janssen adenoviral vector vaccine when both types of COVID-19 vaccine are available.
“Thus, the use of the Janssen vaccine is remarkably low in the U.S. right now,” Dr. Creech said.
“Nevertheless, we have a firm commitment, both scientifically and ethically, to track potential side effects after vaccination and to make sure that the vaccines in use for COVID, and other important infectious diseases, are safe and effective,” he added.
The study had no commercial funding. Dr. Abara and Dr. Creech have reported no relevant financial relationships. Dr. Klein reported having received grants from Pfizer research support for a COVID vaccine clinical trial, as well as grants from Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur).
A version of this article first appeared on Medscape.com.
Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9 to 12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.
Additionally, observed GBS cases after the Janssen shot were 2 to 3 times greater than expected, based on background rates within 21 and 42 days of vaccination.
Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.
The findings were published online in JAMA Network Open.
More precise risk estimates
Winston Abara, MD, with the U.S. Centers for Disease Control and Prevention, and colleagues analyzed GBS reports submitted to the VAERS between December 2020 and January 2022.
Among 487.6 million COVID-19 vaccine doses administered, 3.7% were Janssen’s Ad26.COV2.S vaccine, 54.7% were Pfizer’s BNT162b2 vaccine, and 41.6% were Moderna’s mRNA-1273 vaccine.
There were 295 verified reports of GBS identified after COVID-19 vaccination. Of these, 209 occurred within 21 days of vaccination and 253 within 42 days.
Within 21 days of vaccination, GBS reporting rates per 1 million doses were 3.29 for the Janssen vaccine versus 0.29 and 0.35 for the Pfizer and Moderna vaccines, respectively. Within 42 days of vaccination, reporting rates per 1 million doses were 4.07, 0.34, and 0.44, respectively.
Also within 21 days of vaccination, GBS reporting rates were significantly higher with the Janssen vaccine than the Pfizer vaccine (reporting rate ratio, 11.40) and the Moderna vaccine (RRR, 9.26). Similar findings were observed within 42 days after vaccination.
The observed-to-expected ratios were 3.79 for 21-day and 2.34 for 42-day intervals after receipt of the Janssen vaccine, and less than 1 (not significant) after the Pfizer or Moderna vaccine within both post-vaccination periods.
“Unlike prior studies, our analysis included all U.S. reports of verified GBS cases that met the Brighton Collaboration GBS case definition criteria (Brighton Levels 1, 2, and 3) submitted over a 14-month surveillance period to the to the Vaccine Adverse Event Reporting System,” Dr. Abara said in an interview. “Because we used all U.S. reports, the sample of verified GBS cases in this analysis is larger than other studies. Therefore, it may provide a more precise estimate of the GBS risk within 21 and 42 days after mRNA and Ad26.COV2.S vaccination,” he said.
‘Remarkably low’ use
Nicola Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Oakland, Calif., noted that this is a “nice confirmatory analysis that supports and further expands what’s been observed before.”
Last year, as reported by this news organization, Dr. Klein and colleagues reported data from the Vaccine Safety Datalink confirming a small but statistically significant increased risk for GBS in the 3 weeks after receipt of the Janssen COVID-19 vaccine but not the Pfizer or Moderna vaccines.
Unlike VAERS, the Vaccine Safety Datalink is not a reporting system. It’s an active surveillance of medical records in the Kaiser Permanente system. The VAERS is a passive system, so it requires individuals to report GBS cases to the VAERS team, Dr. Klein explained.
So although the two studies are slightly different, overall, the VAERS data is “consistent with what we found,” she said.
Also weighing in, C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and professor of pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn., said it is “important to realize that GBS had been observed after adenovirus-vectored vaccines earlier in the pandemic, both for the AstraZeneca vaccine and the Janssen vaccine.”
The Advisory Committee on Immunization Practices (ACIP) preferentially recommends that people age 18 years and older receive an mRNA COVID-19 vaccine rather than the Janssen adenoviral vector vaccine when both types of COVID-19 vaccine are available.
“Thus, the use of the Janssen vaccine is remarkably low in the U.S. right now,” Dr. Creech said.
“Nevertheless, we have a firm commitment, both scientifically and ethically, to track potential side effects after vaccination and to make sure that the vaccines in use for COVID, and other important infectious diseases, are safe and effective,” he added.
The study had no commercial funding. Dr. Abara and Dr. Creech have reported no relevant financial relationships. Dr. Klein reported having received grants from Pfizer research support for a COVID vaccine clinical trial, as well as grants from Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur).
A version of this article first appeared on Medscape.com.
Genetic testing in the PICU prompts meaningful changes in care
according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.
“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.
However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.
Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.
After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.
The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.
The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.
Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.
“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”
In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.
Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.
In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.
“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.
Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.
“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.
Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.
Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.
Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.
The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.
“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.
However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.
Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.
After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.
The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.
The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.
Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.
“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”
In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.
Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.
In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.
“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.
Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.
“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.
Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.
Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.
Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.
The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.
“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.
However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.
Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.
After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.
The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.
The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.
Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.
“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”
In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.
Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.
In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.
“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.
Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.
“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.
Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.
Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.
Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.
The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SCCM 2023
Quality of life predicts chemo tolerance in early breast cancer
a new analysis found.
Baseline quality-of-life measures, most often fatigue and physical functioning, have “been associated with survival in various cancers,” the authors explain. These latest findings signal that assessing fatigue and physical functioning prior to treatment “could help to identify patients who are at risk for poor chemotherapy tolerability.”
The findings were published online in the journal Cancer.
Although quality of life is recognized as a predictor of survival in patients with advanced cancer, the evidence is less clear in early-stage breast cancer.
To understand the role quality-of-life measures play in early breast cancer, the investigators performed an ancillary analysis of the French Cancer and Toxicities (CANTO) study, which enrolled women with newly diagnosed stage I-III invasive breast cancer at 26 centers in France.
The ancillary CANTO‐PRED study was designed to explore the association between baseline quality of life measures and chemotherapy dose reductions and postchemotherapy toxicities among 3,079 patients with early breast cancer. This included 718 patients who received chemotherapy in the neoadjuvant setting and 2,361 who received chemotherapy as adjuvant treatment.
Most patients received taxanes (94.2%) and/or anthracyclines (90.5%). Other major adjuvant treatments were breast radiation therapy (92.6%), trastuzumab (21%), and endocrine therapy (74%), and all women underwent either breast-conserving surgery (74%) and/or lymph node dissection (60%). Fatigue and physical functioning were measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.
Among the 3,079 patients, 15.5% experienced chemotherapy dose reductions and 31% developed postchemotherapy toxicities.
After multivariable adjustment for clinical and patient factors, those with baseline fatigue scores greater than 39 (vs. 39 or less) had higher odds of chemotherapy dose reductions (odds ratio, 1.43) and postchemotherapy toxicities (OR, 1.32). Those with baseline physical functioning scores less than 83 (vs. 83 or higher) also had higher odds of chemotherapy dose reductions (OR, 1.54) and postchemotherapy toxicities (OR, 1.50), the authors found.
In addition, cognitive functioning, pain, sleep disturbances, and appetite loss dimensions were associated with both chemotherapy dose reductions and postchemotherapy toxicities, whereas nausea, vomiting, and dyspnea were associated with postchemotherapy toxicities.
The researchers also found that performance status was not associated with chemotherapy dose reductions or postchemotherapy toxicities, suggesting patient-reported quality of life may be a better predictor of outcomes, the authors said.
“The ability to predict important toxicities with baseline information could lead to improvements in the prevention and management of adverse treatment effects by targeting a group of patients who may need [dose reductions] or may have residual toxicities,” the authors concluded.
This study was funded by the French National Research Agency. The authors reported various relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new analysis found.
Baseline quality-of-life measures, most often fatigue and physical functioning, have “been associated with survival in various cancers,” the authors explain. These latest findings signal that assessing fatigue and physical functioning prior to treatment “could help to identify patients who are at risk for poor chemotherapy tolerability.”
The findings were published online in the journal Cancer.
Although quality of life is recognized as a predictor of survival in patients with advanced cancer, the evidence is less clear in early-stage breast cancer.
To understand the role quality-of-life measures play in early breast cancer, the investigators performed an ancillary analysis of the French Cancer and Toxicities (CANTO) study, which enrolled women with newly diagnosed stage I-III invasive breast cancer at 26 centers in France.
The ancillary CANTO‐PRED study was designed to explore the association between baseline quality of life measures and chemotherapy dose reductions and postchemotherapy toxicities among 3,079 patients with early breast cancer. This included 718 patients who received chemotherapy in the neoadjuvant setting and 2,361 who received chemotherapy as adjuvant treatment.
Most patients received taxanes (94.2%) and/or anthracyclines (90.5%). Other major adjuvant treatments were breast radiation therapy (92.6%), trastuzumab (21%), and endocrine therapy (74%), and all women underwent either breast-conserving surgery (74%) and/or lymph node dissection (60%). Fatigue and physical functioning were measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.
Among the 3,079 patients, 15.5% experienced chemotherapy dose reductions and 31% developed postchemotherapy toxicities.
After multivariable adjustment for clinical and patient factors, those with baseline fatigue scores greater than 39 (vs. 39 or less) had higher odds of chemotherapy dose reductions (odds ratio, 1.43) and postchemotherapy toxicities (OR, 1.32). Those with baseline physical functioning scores less than 83 (vs. 83 or higher) also had higher odds of chemotherapy dose reductions (OR, 1.54) and postchemotherapy toxicities (OR, 1.50), the authors found.
In addition, cognitive functioning, pain, sleep disturbances, and appetite loss dimensions were associated with both chemotherapy dose reductions and postchemotherapy toxicities, whereas nausea, vomiting, and dyspnea were associated with postchemotherapy toxicities.
The researchers also found that performance status was not associated with chemotherapy dose reductions or postchemotherapy toxicities, suggesting patient-reported quality of life may be a better predictor of outcomes, the authors said.
“The ability to predict important toxicities with baseline information could lead to improvements in the prevention and management of adverse treatment effects by targeting a group of patients who may need [dose reductions] or may have residual toxicities,” the authors concluded.
This study was funded by the French National Research Agency. The authors reported various relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new analysis found.
Baseline quality-of-life measures, most often fatigue and physical functioning, have “been associated with survival in various cancers,” the authors explain. These latest findings signal that assessing fatigue and physical functioning prior to treatment “could help to identify patients who are at risk for poor chemotherapy tolerability.”
The findings were published online in the journal Cancer.
Although quality of life is recognized as a predictor of survival in patients with advanced cancer, the evidence is less clear in early-stage breast cancer.
To understand the role quality-of-life measures play in early breast cancer, the investigators performed an ancillary analysis of the French Cancer and Toxicities (CANTO) study, which enrolled women with newly diagnosed stage I-III invasive breast cancer at 26 centers in France.
The ancillary CANTO‐PRED study was designed to explore the association between baseline quality of life measures and chemotherapy dose reductions and postchemotherapy toxicities among 3,079 patients with early breast cancer. This included 718 patients who received chemotherapy in the neoadjuvant setting and 2,361 who received chemotherapy as adjuvant treatment.
Most patients received taxanes (94.2%) and/or anthracyclines (90.5%). Other major adjuvant treatments were breast radiation therapy (92.6%), trastuzumab (21%), and endocrine therapy (74%), and all women underwent either breast-conserving surgery (74%) and/or lymph node dissection (60%). Fatigue and physical functioning were measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.
Among the 3,079 patients, 15.5% experienced chemotherapy dose reductions and 31% developed postchemotherapy toxicities.
After multivariable adjustment for clinical and patient factors, those with baseline fatigue scores greater than 39 (vs. 39 or less) had higher odds of chemotherapy dose reductions (odds ratio, 1.43) and postchemotherapy toxicities (OR, 1.32). Those with baseline physical functioning scores less than 83 (vs. 83 or higher) also had higher odds of chemotherapy dose reductions (OR, 1.54) and postchemotherapy toxicities (OR, 1.50), the authors found.
In addition, cognitive functioning, pain, sleep disturbances, and appetite loss dimensions were associated with both chemotherapy dose reductions and postchemotherapy toxicities, whereas nausea, vomiting, and dyspnea were associated with postchemotherapy toxicities.
The researchers also found that performance status was not associated with chemotherapy dose reductions or postchemotherapy toxicities, suggesting patient-reported quality of life may be a better predictor of outcomes, the authors said.
“The ability to predict important toxicities with baseline information could lead to improvements in the prevention and management of adverse treatment effects by targeting a group of patients who may need [dose reductions] or may have residual toxicities,” the authors concluded.
This study was funded by the French National Research Agency. The authors reported various relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANCER
Black patients less likely to receive opioids for advanced cancer
Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, a new study suggests.
Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.
The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”
The study was published on in the Journal of Clinical Oncology.
The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.
The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.
Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.
Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).
“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.
Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.
When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.
“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.
The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.
From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.
Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.
“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”
The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.
The study was supported by a grant from the Agency for Healthcare Research and Policy.
A version of this article first appeared on Medscape.com.
Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, a new study suggests.
Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.
The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”
The study was published on in the Journal of Clinical Oncology.
The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.
The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.
Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.
Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).
“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.
Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.
When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.
“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.
The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.
From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.
Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.
“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”
The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.
The study was supported by a grant from the Agency for Healthcare Research and Policy.
A version of this article first appeared on Medscape.com.
Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, a new study suggests.
Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.
The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”
The study was published on in the Journal of Clinical Oncology.
The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.
The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.
Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.
Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).
“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.
Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.
When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.
“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.
The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.
From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.
Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.
“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”
The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.
The study was supported by a grant from the Agency for Healthcare Research and Policy.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Loneliness risk elevated among young cancer survivors
findings from a large retrospective study suggest.
Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.
“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”
The article was published online in the journal Cancer.
Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.
“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.
To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.
The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.
The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.
Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).
Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).
Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).
Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.
The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.
Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.
“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.
Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.
Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”
Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.
The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.
A version of this article first appeared on Medscape.com.
findings from a large retrospective study suggest.
Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.
“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”
The article was published online in the journal Cancer.
Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.
“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.
To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.
The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.
The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.
Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).
Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).
Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).
Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.
The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.
Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.
“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.
Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.
Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”
Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.
The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.
A version of this article first appeared on Medscape.com.
findings from a large retrospective study suggest.
Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.
“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”
The article was published online in the journal Cancer.
Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.
“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.
To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.
The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.
The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.
Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).
Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).
Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).
Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.
The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.
Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.
“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.
Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.
Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”
Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.
The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.
A version of this article first appeared on Medscape.com.
FROM CANCER
Eating potatoes is healthy, study finds
according to researchers at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.
What to know
Potatoes are filled with key nutrients, packed with health benefits, and do not increase the risk of type 2 diabetes, as has been assumed.
People tend to eat the same weight of food regardless of calorie content to feel full, so by eating foods that are heavier in weight and that are low in calories, you can reduce the number of calories you consume.
Study participants found themselves fuller, and full more quickly, and often did not even finish their meal when the high-calorie items of their meals were replaced with potatoes.
Participants had overweight, obesity, or insulin resistance, but their blood glucose levels were not negatively affected by the potato consumption, and all of those involved actually lost weight.
People typically do not stick with a diet they don’t like or that isn't varied enough, but potatoes can be prepared in numerous ways for variety in a diet, and they are a fairly inexpensive vegetable to incorporate into a diet.
This is a summary of the article, "Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial," published in the Journal of Medicinal Food on November 11, 2022. The full article can be found on pubmed.ncbi.nlm.nih.gov.
A version of this article first appeared on Medscape.com.
according to researchers at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.
What to know
Potatoes are filled with key nutrients, packed with health benefits, and do not increase the risk of type 2 diabetes, as has been assumed.
People tend to eat the same weight of food regardless of calorie content to feel full, so by eating foods that are heavier in weight and that are low in calories, you can reduce the number of calories you consume.
Study participants found themselves fuller, and full more quickly, and often did not even finish their meal when the high-calorie items of their meals were replaced with potatoes.
Participants had overweight, obesity, or insulin resistance, but their blood glucose levels were not negatively affected by the potato consumption, and all of those involved actually lost weight.
People typically do not stick with a diet they don’t like or that isn't varied enough, but potatoes can be prepared in numerous ways for variety in a diet, and they are a fairly inexpensive vegetable to incorporate into a diet.
This is a summary of the article, "Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial," published in the Journal of Medicinal Food on November 11, 2022. The full article can be found on pubmed.ncbi.nlm.nih.gov.
A version of this article first appeared on Medscape.com.
according to researchers at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.
What to know
Potatoes are filled with key nutrients, packed with health benefits, and do not increase the risk of type 2 diabetes, as has been assumed.
People tend to eat the same weight of food regardless of calorie content to feel full, so by eating foods that are heavier in weight and that are low in calories, you can reduce the number of calories you consume.
Study participants found themselves fuller, and full more quickly, and often did not even finish their meal when the high-calorie items of their meals were replaced with potatoes.
Participants had overweight, obesity, or insulin resistance, but their blood glucose levels were not negatively affected by the potato consumption, and all of those involved actually lost weight.
People typically do not stick with a diet they don’t like or that isn't varied enough, but potatoes can be prepared in numerous ways for variety in a diet, and they are a fairly inexpensive vegetable to incorporate into a diet.
This is a summary of the article, "Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial," published in the Journal of Medicinal Food on November 11, 2022. The full article can be found on pubmed.ncbi.nlm.nih.gov.
A version of this article first appeared on Medscape.com.
A Dermatology Hospitalist Team’s Response to the Inpatient Consult Flowchart
To the Editor:
We read with interest the Cutis article by Dobkin et al1 (Cutis. 2022;109:218-220) regarding guidelines for inpatient and emergency department dermatology consultations. We agree with the authors that dermatology training is lacking in other medical specialties, which makes it challenging for teams to assess the appropriateness of a dermatology consultation in the inpatient setting. Inpatient dermatology consultation can be utilized in a hospital system to aid in rapid and accurate diagnosis, avoid inappropriate therapies, and decrease length of stay2 and readmission rates3 while providing education to the primary teams. This is precisely why in many instances the availability of inpatient dermatology consultation is so important because nondermatologists often are unable to determine whether a rash is life-threatening, benign, or something in between. From the perspective of dermatology hospitalists, there is room for improvement in the flowchart Dobkin et al1 presented to guide inpatient dermatology consultation.
To have a productive relationship with our internal medicine, surgery, pediatrics, psychiatry, and other hospital-based colleagues, we must keep an open mind when a consultation is received. We feel that the flowchart proposed by Dobkin et al1 presents too narrow a viewpoint on the utility of inpatient dermatology. It rests on assertions that other teams will be able to determine the appropriate dermatologic diagnosis without involving a dermatologist, which often is not the case.
We disagree with several recommendations in the flowchart, the first being the assertion that patients who are “hemodynamically unstable due to [a] nondermatologic problem (eg, intubated on pressors, febrile, and hypotensive)” are not appropriate for inpatient dermatology consultation.1 Although dermatologists do not commonly encounter patients with critical illness in the outpatient clinic, dermatology consultation can be extremely helpful and even lifesaving in the inpatient setting. It is unrealistic to expect the primary teams to know whether cutaneous manifestations potentially could be related to the patient’s overall clinical picture. On the contrary, we would encourage the primary team in charge of a hemodynamically unstable patient to consult dermatology at the first sign of an unexplained rash. Take for example an acutely ill patient who develops retiform purpura. There are well-established dermatology guidelines for the workup of retiform purpura,4 including prompt biopsy and assessment of broad, potentially life-threatening differential diagnoses from calciphylaxis to angioinvasive fungal infection. In this scenario, the dermatology consultant may render the correct diagnosis and recommend immediate treatment that could be lifesaving.
Secondly, we do not agree with the recommendation that a patient in hospice care is not appropriate for inpatient dermatology consultation. Patients receiving hospice or palliative care have high rates of potentially symptomatic cutaneous diseases,5 including intertrigo and dermatitis—comprising stasis, seborrheic, and contact dermatitis.6 Although aggressive intervention for asymptomatic benign or malignant skin conditions may not be in line with their goals of care, an inpatient dermatology consultation can reduce symptoms and improve quality of life. This population also is one that is unlikely to be able to attend an outpatient dermatology clinic appointment and therefore are good candidates for inpatient consultation.
Lastly, we want to highlight the difference between a stable chronic dermatologic disease and an acute flare that may occur while a patient is hospitalized, regardless of whether it is the reason for admission. For example, a patient with psoriasis affecting limited body surface area who is hospitalized for a myocardial infarction is not appropriate for a dermatology consultation. However, if that same patient develops erythroderma while they are hospitalized for cardiac monitoring, it would certainly be appropriate for dermatology to be consulted. Additionally, there are times when a chronic skin disease is the reason for hospitalization; dermatology, although technically a consulting service, would be the primary decision-maker for the patient’s care in this situation. In these scenarios, it is important for the patient to be able to establish care for long-term outpatient management of their condition; however, it is prudent to involve dermatology while the patient is acutely hospitalized to guide their treatment plan until they are able to see a dermatologist after discharge.
In conclusion, we believe that hospital dermatology is a valuable tool that can be utilized in many different scenarios. Although there are certainly situations more appropriate for outpatient dermatology referral, we would caution against overly simplified algorithms that could discourage valuable inpatient dermatology consultations. It often is worth a conversation with your dermatology consultant (when available at an institution) to determine the best course of action for each patient. Additionally, we recognize the need for more formalized guidelines on when to pursue inpatient dermatology consultation. We are members of the Society of Dermatology Hospitalists and encourage readers to reference their website, which provides additional resources on inpatient dermatology (https://societydermatologyhospitalists.com/inpatient-dermatology-literature/).
Authors’ Response
We appreciate the letter in response to our commentary on the appropriateness of inpatient dermatology consultations. It is the continued refining and re-evaluation of concepts such as these that allow our field to grow and improve knowledge and patient care.
We sought to provide a nonpatronizing yet simple consultation flowchart that would help guide triage of patients in need or not in need of dermatologic evaluation by the inpatient teams. Understandably, the impressions of our flowchart have been variable based on different readers’ medical backgrounds and experiences. It is certainly possible that our flowchart lacked certain exceptions and oversimplified certain concepts, and we welcome further refining of this flowchart to better guide inpatient dermatology consultations.
We do, however, disagree that the primary team would not know whether a patient is intubated in the intensive care unit for a dermatology reason. If the patient is in such a status, it would be pertinent for the primary team to conduct a timely workup that could include consultations until a diagnosis is made. We were not implying that every dermatology consultation in the intensive care unit is unwarranted, especially if it can lead to a primary dermatologic diagnosis. We do believe that a thorough history could elicit an allergy or other chronic skin condition that could save resources and spending within a hospital. Likewise, psoriasis comes in many different presentations, and although we do not believe a consultation for chronic psoriatic plaques is appropriate in the hospital, it is absolutely appropriate for a patient who is erythrodermic from any cause.
Our flowchart was intended to be the first step to providing education on when consultations are appropriate, and further refinement will be necessary.
Hershel Dobkin, MD; Timothy Blackwell, BS; Robin Ashinoff, MD
Drs. Dobkin and Ashinoff are from Hackensack University Medical Center, New Jersey. Mr. Blackwell is from the Rowan University School of Osteopathic Medicine, Stratford, New Jersey.
The authors report no conflict of interest.
Correspondence: Hershel Dobkin, MD, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601 ([email protected]).
- Dobkin H, Blackwell T, Ashinoff R. When are inpatient and emergency dermatologic consultations appropriate? Cutis. 2022;109:218-220. doi:10.12788/cutis.0492
- Ko LN, Garza-Mayers AC, St John J, et al. Effect of dermatology consultation on outcomes for patients with presumed cellulitis: a randomized clinical trial. JAMA Dermatol. 2018;154:529-536. doi:10.1001/jamadermatol.2017.6196
- Hu L, Haynes H, Ferrazza D, et al. Impact of specialist consultations on inpatient admissions for dermatology-specific and related DRGs. J Gen Intern Med. 2013;28:1477-1482. doi:10.1007/s11606-013-2440-2
- Georgesen C, Fox LP, Harp J. Retiform purpura: a diagnostic approach. J Am Acad Dermatol. 2020;82:783-796. doi:10.1016/j.jaad.2019.07.112
- Pisano C, Paladichuk H, Keeling B. Dermatology in palliative medicine [published online October 14, 2021]. BMJ Support Palliat Care. doi:10.1136/bmjspcare-2021-003342
- Barnabé C, Daeninck P. “Beauty is only skin deep”: prevalence of dermatologic disease on a palliative care unit. J Pain Symptom Manage. 2005;29:419-422. doi:10.1016/j.jpainsymman.2004.08.009
To the Editor:
We read with interest the Cutis article by Dobkin et al1 (Cutis. 2022;109:218-220) regarding guidelines for inpatient and emergency department dermatology consultations. We agree with the authors that dermatology training is lacking in other medical specialties, which makes it challenging for teams to assess the appropriateness of a dermatology consultation in the inpatient setting. Inpatient dermatology consultation can be utilized in a hospital system to aid in rapid and accurate diagnosis, avoid inappropriate therapies, and decrease length of stay2 and readmission rates3 while providing education to the primary teams. This is precisely why in many instances the availability of inpatient dermatology consultation is so important because nondermatologists often are unable to determine whether a rash is life-threatening, benign, or something in between. From the perspective of dermatology hospitalists, there is room for improvement in the flowchart Dobkin et al1 presented to guide inpatient dermatology consultation.
To have a productive relationship with our internal medicine, surgery, pediatrics, psychiatry, and other hospital-based colleagues, we must keep an open mind when a consultation is received. We feel that the flowchart proposed by Dobkin et al1 presents too narrow a viewpoint on the utility of inpatient dermatology. It rests on assertions that other teams will be able to determine the appropriate dermatologic diagnosis without involving a dermatologist, which often is not the case.
We disagree with several recommendations in the flowchart, the first being the assertion that patients who are “hemodynamically unstable due to [a] nondermatologic problem (eg, intubated on pressors, febrile, and hypotensive)” are not appropriate for inpatient dermatology consultation.1 Although dermatologists do not commonly encounter patients with critical illness in the outpatient clinic, dermatology consultation can be extremely helpful and even lifesaving in the inpatient setting. It is unrealistic to expect the primary teams to know whether cutaneous manifestations potentially could be related to the patient’s overall clinical picture. On the contrary, we would encourage the primary team in charge of a hemodynamically unstable patient to consult dermatology at the first sign of an unexplained rash. Take for example an acutely ill patient who develops retiform purpura. There are well-established dermatology guidelines for the workup of retiform purpura,4 including prompt biopsy and assessment of broad, potentially life-threatening differential diagnoses from calciphylaxis to angioinvasive fungal infection. In this scenario, the dermatology consultant may render the correct diagnosis and recommend immediate treatment that could be lifesaving.
Secondly, we do not agree with the recommendation that a patient in hospice care is not appropriate for inpatient dermatology consultation. Patients receiving hospice or palliative care have high rates of potentially symptomatic cutaneous diseases,5 including intertrigo and dermatitis—comprising stasis, seborrheic, and contact dermatitis.6 Although aggressive intervention for asymptomatic benign or malignant skin conditions may not be in line with their goals of care, an inpatient dermatology consultation can reduce symptoms and improve quality of life. This population also is one that is unlikely to be able to attend an outpatient dermatology clinic appointment and therefore are good candidates for inpatient consultation.
Lastly, we want to highlight the difference between a stable chronic dermatologic disease and an acute flare that may occur while a patient is hospitalized, regardless of whether it is the reason for admission. For example, a patient with psoriasis affecting limited body surface area who is hospitalized for a myocardial infarction is not appropriate for a dermatology consultation. However, if that same patient develops erythroderma while they are hospitalized for cardiac monitoring, it would certainly be appropriate for dermatology to be consulted. Additionally, there are times when a chronic skin disease is the reason for hospitalization; dermatology, although technically a consulting service, would be the primary decision-maker for the patient’s care in this situation. In these scenarios, it is important for the patient to be able to establish care for long-term outpatient management of their condition; however, it is prudent to involve dermatology while the patient is acutely hospitalized to guide their treatment plan until they are able to see a dermatologist after discharge.
In conclusion, we believe that hospital dermatology is a valuable tool that can be utilized in many different scenarios. Although there are certainly situations more appropriate for outpatient dermatology referral, we would caution against overly simplified algorithms that could discourage valuable inpatient dermatology consultations. It often is worth a conversation with your dermatology consultant (when available at an institution) to determine the best course of action for each patient. Additionally, we recognize the need for more formalized guidelines on when to pursue inpatient dermatology consultation. We are members of the Society of Dermatology Hospitalists and encourage readers to reference their website, which provides additional resources on inpatient dermatology (https://societydermatologyhospitalists.com/inpatient-dermatology-literature/).
Authors’ Response
We appreciate the letter in response to our commentary on the appropriateness of inpatient dermatology consultations. It is the continued refining and re-evaluation of concepts such as these that allow our field to grow and improve knowledge and patient care.
We sought to provide a nonpatronizing yet simple consultation flowchart that would help guide triage of patients in need or not in need of dermatologic evaluation by the inpatient teams. Understandably, the impressions of our flowchart have been variable based on different readers’ medical backgrounds and experiences. It is certainly possible that our flowchart lacked certain exceptions and oversimplified certain concepts, and we welcome further refining of this flowchart to better guide inpatient dermatology consultations.
We do, however, disagree that the primary team would not know whether a patient is intubated in the intensive care unit for a dermatology reason. If the patient is in such a status, it would be pertinent for the primary team to conduct a timely workup that could include consultations until a diagnosis is made. We were not implying that every dermatology consultation in the intensive care unit is unwarranted, especially if it can lead to a primary dermatologic diagnosis. We do believe that a thorough history could elicit an allergy or other chronic skin condition that could save resources and spending within a hospital. Likewise, psoriasis comes in many different presentations, and although we do not believe a consultation for chronic psoriatic plaques is appropriate in the hospital, it is absolutely appropriate for a patient who is erythrodermic from any cause.
Our flowchart was intended to be the first step to providing education on when consultations are appropriate, and further refinement will be necessary.
Hershel Dobkin, MD; Timothy Blackwell, BS; Robin Ashinoff, MD
Drs. Dobkin and Ashinoff are from Hackensack University Medical Center, New Jersey. Mr. Blackwell is from the Rowan University School of Osteopathic Medicine, Stratford, New Jersey.
The authors report no conflict of interest.
Correspondence: Hershel Dobkin, MD, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601 ([email protected]).
To the Editor:
We read with interest the Cutis article by Dobkin et al1 (Cutis. 2022;109:218-220) regarding guidelines for inpatient and emergency department dermatology consultations. We agree with the authors that dermatology training is lacking in other medical specialties, which makes it challenging for teams to assess the appropriateness of a dermatology consultation in the inpatient setting. Inpatient dermatology consultation can be utilized in a hospital system to aid in rapid and accurate diagnosis, avoid inappropriate therapies, and decrease length of stay2 and readmission rates3 while providing education to the primary teams. This is precisely why in many instances the availability of inpatient dermatology consultation is so important because nondermatologists often are unable to determine whether a rash is life-threatening, benign, or something in between. From the perspective of dermatology hospitalists, there is room for improvement in the flowchart Dobkin et al1 presented to guide inpatient dermatology consultation.
To have a productive relationship with our internal medicine, surgery, pediatrics, psychiatry, and other hospital-based colleagues, we must keep an open mind when a consultation is received. We feel that the flowchart proposed by Dobkin et al1 presents too narrow a viewpoint on the utility of inpatient dermatology. It rests on assertions that other teams will be able to determine the appropriate dermatologic diagnosis without involving a dermatologist, which often is not the case.
We disagree with several recommendations in the flowchart, the first being the assertion that patients who are “hemodynamically unstable due to [a] nondermatologic problem (eg, intubated on pressors, febrile, and hypotensive)” are not appropriate for inpatient dermatology consultation.1 Although dermatologists do not commonly encounter patients with critical illness in the outpatient clinic, dermatology consultation can be extremely helpful and even lifesaving in the inpatient setting. It is unrealistic to expect the primary teams to know whether cutaneous manifestations potentially could be related to the patient’s overall clinical picture. On the contrary, we would encourage the primary team in charge of a hemodynamically unstable patient to consult dermatology at the first sign of an unexplained rash. Take for example an acutely ill patient who develops retiform purpura. There are well-established dermatology guidelines for the workup of retiform purpura,4 including prompt biopsy and assessment of broad, potentially life-threatening differential diagnoses from calciphylaxis to angioinvasive fungal infection. In this scenario, the dermatology consultant may render the correct diagnosis and recommend immediate treatment that could be lifesaving.
Secondly, we do not agree with the recommendation that a patient in hospice care is not appropriate for inpatient dermatology consultation. Patients receiving hospice or palliative care have high rates of potentially symptomatic cutaneous diseases,5 including intertrigo and dermatitis—comprising stasis, seborrheic, and contact dermatitis.6 Although aggressive intervention for asymptomatic benign or malignant skin conditions may not be in line with their goals of care, an inpatient dermatology consultation can reduce symptoms and improve quality of life. This population also is one that is unlikely to be able to attend an outpatient dermatology clinic appointment and therefore are good candidates for inpatient consultation.
Lastly, we want to highlight the difference between a stable chronic dermatologic disease and an acute flare that may occur while a patient is hospitalized, regardless of whether it is the reason for admission. For example, a patient with psoriasis affecting limited body surface area who is hospitalized for a myocardial infarction is not appropriate for a dermatology consultation. However, if that same patient develops erythroderma while they are hospitalized for cardiac monitoring, it would certainly be appropriate for dermatology to be consulted. Additionally, there are times when a chronic skin disease is the reason for hospitalization; dermatology, although technically a consulting service, would be the primary decision-maker for the patient’s care in this situation. In these scenarios, it is important for the patient to be able to establish care for long-term outpatient management of their condition; however, it is prudent to involve dermatology while the patient is acutely hospitalized to guide their treatment plan until they are able to see a dermatologist after discharge.
In conclusion, we believe that hospital dermatology is a valuable tool that can be utilized in many different scenarios. Although there are certainly situations more appropriate for outpatient dermatology referral, we would caution against overly simplified algorithms that could discourage valuable inpatient dermatology consultations. It often is worth a conversation with your dermatology consultant (when available at an institution) to determine the best course of action for each patient. Additionally, we recognize the need for more formalized guidelines on when to pursue inpatient dermatology consultation. We are members of the Society of Dermatology Hospitalists and encourage readers to reference their website, which provides additional resources on inpatient dermatology (https://societydermatologyhospitalists.com/inpatient-dermatology-literature/).
Authors’ Response
We appreciate the letter in response to our commentary on the appropriateness of inpatient dermatology consultations. It is the continued refining and re-evaluation of concepts such as these that allow our field to grow and improve knowledge and patient care.
We sought to provide a nonpatronizing yet simple consultation flowchart that would help guide triage of patients in need or not in need of dermatologic evaluation by the inpatient teams. Understandably, the impressions of our flowchart have been variable based on different readers’ medical backgrounds and experiences. It is certainly possible that our flowchart lacked certain exceptions and oversimplified certain concepts, and we welcome further refining of this flowchart to better guide inpatient dermatology consultations.
We do, however, disagree that the primary team would not know whether a patient is intubated in the intensive care unit for a dermatology reason. If the patient is in such a status, it would be pertinent for the primary team to conduct a timely workup that could include consultations until a diagnosis is made. We were not implying that every dermatology consultation in the intensive care unit is unwarranted, especially if it can lead to a primary dermatologic diagnosis. We do believe that a thorough history could elicit an allergy or other chronic skin condition that could save resources and spending within a hospital. Likewise, psoriasis comes in many different presentations, and although we do not believe a consultation for chronic psoriatic plaques is appropriate in the hospital, it is absolutely appropriate for a patient who is erythrodermic from any cause.
Our flowchart was intended to be the first step to providing education on when consultations are appropriate, and further refinement will be necessary.
Hershel Dobkin, MD; Timothy Blackwell, BS; Robin Ashinoff, MD
Drs. Dobkin and Ashinoff are from Hackensack University Medical Center, New Jersey. Mr. Blackwell is from the Rowan University School of Osteopathic Medicine, Stratford, New Jersey.
The authors report no conflict of interest.
Correspondence: Hershel Dobkin, MD, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601 ([email protected]).
- Dobkin H, Blackwell T, Ashinoff R. When are inpatient and emergency dermatologic consultations appropriate? Cutis. 2022;109:218-220. doi:10.12788/cutis.0492
- Ko LN, Garza-Mayers AC, St John J, et al. Effect of dermatology consultation on outcomes for patients with presumed cellulitis: a randomized clinical trial. JAMA Dermatol. 2018;154:529-536. doi:10.1001/jamadermatol.2017.6196
- Hu L, Haynes H, Ferrazza D, et al. Impact of specialist consultations on inpatient admissions for dermatology-specific and related DRGs. J Gen Intern Med. 2013;28:1477-1482. doi:10.1007/s11606-013-2440-2
- Georgesen C, Fox LP, Harp J. Retiform purpura: a diagnostic approach. J Am Acad Dermatol. 2020;82:783-796. doi:10.1016/j.jaad.2019.07.112
- Pisano C, Paladichuk H, Keeling B. Dermatology in palliative medicine [published online October 14, 2021]. BMJ Support Palliat Care. doi:10.1136/bmjspcare-2021-003342
- Barnabé C, Daeninck P. “Beauty is only skin deep”: prevalence of dermatologic disease on a palliative care unit. J Pain Symptom Manage. 2005;29:419-422. doi:10.1016/j.jpainsymman.2004.08.009
- Dobkin H, Blackwell T, Ashinoff R. When are inpatient and emergency dermatologic consultations appropriate? Cutis. 2022;109:218-220. doi:10.12788/cutis.0492
- Ko LN, Garza-Mayers AC, St John J, et al. Effect of dermatology consultation on outcomes for patients with presumed cellulitis: a randomized clinical trial. JAMA Dermatol. 2018;154:529-536. doi:10.1001/jamadermatol.2017.6196
- Hu L, Haynes H, Ferrazza D, et al. Impact of specialist consultations on inpatient admissions for dermatology-specific and related DRGs. J Gen Intern Med. 2013;28:1477-1482. doi:10.1007/s11606-013-2440-2
- Georgesen C, Fox LP, Harp J. Retiform purpura: a diagnostic approach. J Am Acad Dermatol. 2020;82:783-796. doi:10.1016/j.jaad.2019.07.112
- Pisano C, Paladichuk H, Keeling B. Dermatology in palliative medicine [published online October 14, 2021]. BMJ Support Palliat Care. doi:10.1136/bmjspcare-2021-003342
- Barnabé C, Daeninck P. “Beauty is only skin deep”: prevalence of dermatologic disease on a palliative care unit. J Pain Symptom Manage. 2005;29:419-422. doi:10.1016/j.jpainsymman.2004.08.009
Vitiligo
THE COMPARISON
A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband UVB treatment.
B Vitiligo on the hand in a young Hispanic male.
Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.1 Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.2
Epidemiology
Vitiligo affects approximately 1% of the US population and up to 8% worldwide.2 There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.1
Key clinical features in people with darker skin tones
Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (Figures A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.2 Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.2
An important distinction when diagnosing vitiligo is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.3
Worth noting
Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.4,5
Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.1 In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients 12 years and older.6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase– signal transducers and activators of the transcription pathway.6 However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.8
Health disparity highlight
A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.7 In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.11 Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).12
Final thoughts
US Food and Drug Administration approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.13
- Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin. 2017;35:257-265. doi:10.1016/j.det.2016.11.014
- Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive overview part I. introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65:473-491. doi:10.1016/j.jaad.2010.11.061
- van Geel N, Speeckaert R. Segmental vitiligo. Dermatol Clin. 2017; 35:145-150. doi:10.1016/j.det.2016.11.005
- Grimes PE, Miller MM. Vitiligo: patient stories, self-esteem, and the psychological burden of disease. Int J Womens Dermatol. 2018;4:32-37. doi:10.1016/j.ijwd.2017.11.005
- Ezzedine K, Eleftheriadou V, Jones H, et al. Psychosocial effects of vitiligo: a systematic literature review [published online September 23, 2021]. Am J Clin Dermatol. 2021;22:757-774. doi:10.1007/s40257 -021-00631-6
- FDA approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older. News release. US Food and Drug Administration; July 19, 2022. Accessed December 27, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients -aged-12-and-older
- Blundell A, Sachar M, Gabel CK, et al. The scope of health insurance coverage of vitiligo treatments in the United States: implications for health care outcomes and disparities in children of color [published online July 16, 2021]. Pediatr Dermatol. 2021; 38(suppl 2):79-85. doi:10.1111/pde.14714
- Opzelura prices, coupons, and patient assistance programs. Drugs.com. Accessed January 10, 2023. https://www.drugs.com /price-guide/opzelura#:~:text=Opzelura%20Prices%2C%20 Coupons%20and%20Patient,on%20the%20pharmacy%20you%20visit
- Bhutani T, Liao W. A practical approach to home UVB phototherapy for the treatment of generalized psoriasis. Pract Dermatol. 2010;7:31-35.
- Castro Porto Silva Lopes F, Ahmed A. Insurance coverage for phototherapy for vitiligo in comparison to psoriasis and atopic dermatitis. SKIN The Journal of Cutaneous Medicine. 2022;6:217-224. https://doi.org/10.25251/skin.6.3.6
- Smith MP, Ly K, Thibodeaux Q, et al. Home phototherapy for patients with vitiligo: challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:451-459. doi:10.2147/CCID.S185798
- Shrider EA, Kollar M, Chen F, et al. Income and poverty in the United States: 2020. US Census Bureau. September 14, 2021. Accessed December 27, 2022. https://www.census.gov/library/publications/2021/demo/p60-273.html
- Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. Cochrane Database Syst Rev. 2010;(1):CD003263. doi:10.1002/14651858.CD003263.pub4
THE COMPARISON
A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband UVB treatment.
B Vitiligo on the hand in a young Hispanic male.
Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.1 Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.2
Epidemiology
Vitiligo affects approximately 1% of the US population and up to 8% worldwide.2 There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.1
Key clinical features in people with darker skin tones
Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (Figures A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.2 Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.2
An important distinction when diagnosing vitiligo is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.3
Worth noting
Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.4,5
Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.1 In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients 12 years and older.6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase– signal transducers and activators of the transcription pathway.6 However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.8
Health disparity highlight
A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.7 In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.11 Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).12
Final thoughts
US Food and Drug Administration approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.13
THE COMPARISON
A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband UVB treatment.
B Vitiligo on the hand in a young Hispanic male.
Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.1 Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.2
Epidemiology
Vitiligo affects approximately 1% of the US population and up to 8% worldwide.2 There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.1
Key clinical features in people with darker skin tones
Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (Figures A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.2 Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.2
An important distinction when diagnosing vitiligo is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.3
Worth noting
Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.4,5
Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.1 In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients 12 years and older.6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase– signal transducers and activators of the transcription pathway.6 However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.8
Health disparity highlight
A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.7 In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.11 Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).12
Final thoughts
US Food and Drug Administration approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.13
- Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin. 2017;35:257-265. doi:10.1016/j.det.2016.11.014
- Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive overview part I. introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65:473-491. doi:10.1016/j.jaad.2010.11.061
- van Geel N, Speeckaert R. Segmental vitiligo. Dermatol Clin. 2017; 35:145-150. doi:10.1016/j.det.2016.11.005
- Grimes PE, Miller MM. Vitiligo: patient stories, self-esteem, and the psychological burden of disease. Int J Womens Dermatol. 2018;4:32-37. doi:10.1016/j.ijwd.2017.11.005
- Ezzedine K, Eleftheriadou V, Jones H, et al. Psychosocial effects of vitiligo: a systematic literature review [published online September 23, 2021]. Am J Clin Dermatol. 2021;22:757-774. doi:10.1007/s40257 -021-00631-6
- FDA approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older. News release. US Food and Drug Administration; July 19, 2022. Accessed December 27, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients -aged-12-and-older
- Blundell A, Sachar M, Gabel CK, et al. The scope of health insurance coverage of vitiligo treatments in the United States: implications for health care outcomes and disparities in children of color [published online July 16, 2021]. Pediatr Dermatol. 2021; 38(suppl 2):79-85. doi:10.1111/pde.14714
- Opzelura prices, coupons, and patient assistance programs. Drugs.com. Accessed January 10, 2023. https://www.drugs.com /price-guide/opzelura#:~:text=Opzelura%20Prices%2C%20 Coupons%20and%20Patient,on%20the%20pharmacy%20you%20visit
- Bhutani T, Liao W. A practical approach to home UVB phototherapy for the treatment of generalized psoriasis. Pract Dermatol. 2010;7:31-35.
- Castro Porto Silva Lopes F, Ahmed A. Insurance coverage for phototherapy for vitiligo in comparison to psoriasis and atopic dermatitis. SKIN The Journal of Cutaneous Medicine. 2022;6:217-224. https://doi.org/10.25251/skin.6.3.6
- Smith MP, Ly K, Thibodeaux Q, et al. Home phototherapy for patients with vitiligo: challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:451-459. doi:10.2147/CCID.S185798
- Shrider EA, Kollar M, Chen F, et al. Income and poverty in the United States: 2020. US Census Bureau. September 14, 2021. Accessed December 27, 2022. https://www.census.gov/library/publications/2021/demo/p60-273.html
- Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. Cochrane Database Syst Rev. 2010;(1):CD003263. doi:10.1002/14651858.CD003263.pub4
- Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin. 2017;35:257-265. doi:10.1016/j.det.2016.11.014
- Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive overview part I. introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65:473-491. doi:10.1016/j.jaad.2010.11.061
- van Geel N, Speeckaert R. Segmental vitiligo. Dermatol Clin. 2017; 35:145-150. doi:10.1016/j.det.2016.11.005
- Grimes PE, Miller MM. Vitiligo: patient stories, self-esteem, and the psychological burden of disease. Int J Womens Dermatol. 2018;4:32-37. doi:10.1016/j.ijwd.2017.11.005
- Ezzedine K, Eleftheriadou V, Jones H, et al. Psychosocial effects of vitiligo: a systematic literature review [published online September 23, 2021]. Am J Clin Dermatol. 2021;22:757-774. doi:10.1007/s40257 -021-00631-6
- FDA approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older. News release. US Food and Drug Administration; July 19, 2022. Accessed December 27, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients -aged-12-and-older
- Blundell A, Sachar M, Gabel CK, et al. The scope of health insurance coverage of vitiligo treatments in the United States: implications for health care outcomes and disparities in children of color [published online July 16, 2021]. Pediatr Dermatol. 2021; 38(suppl 2):79-85. doi:10.1111/pde.14714
- Opzelura prices, coupons, and patient assistance programs. Drugs.com. Accessed January 10, 2023. https://www.drugs.com /price-guide/opzelura#:~:text=Opzelura%20Prices%2C%20 Coupons%20and%20Patient,on%20the%20pharmacy%20you%20visit
- Bhutani T, Liao W. A practical approach to home UVB phototherapy for the treatment of generalized psoriasis. Pract Dermatol. 2010;7:31-35.
- Castro Porto Silva Lopes F, Ahmed A. Insurance coverage for phototherapy for vitiligo in comparison to psoriasis and atopic dermatitis. SKIN The Journal of Cutaneous Medicine. 2022;6:217-224. https://doi.org/10.25251/skin.6.3.6
- Smith MP, Ly K, Thibodeaux Q, et al. Home phototherapy for patients with vitiligo: challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:451-459. doi:10.2147/CCID.S185798
- Shrider EA, Kollar M, Chen F, et al. Income and poverty in the United States: 2020. US Census Bureau. September 14, 2021. Accessed December 27, 2022. https://www.census.gov/library/publications/2021/demo/p60-273.html
- Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. Cochrane Database Syst Rev. 2010;(1):CD003263. doi:10.1002/14651858.CD003263.pub4
Perceived barriers to accessing psychiatric electroceutical interventions for depression
Psychiatric electroceutical interventions (PEIs) – including Food and Drug Administration–approved therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), as well as experimental interventions such as deep brain stimulation (DBS) and adaptive brain implants (ABI) – offer therapeutic promise for patients suffering with major depressive disorder (MDD). Yet there remain many open questions regarding their use, even in cases where their safety and effectiveness is well established.
Our research aims to better understand how different stakeholder groups view these interventions. We conducted a series of interviews with psychiatrists, patients with MDD, and members of the public to more fully comprehend these groups’ perceptions of barriers to using these therapies.1 They raised concerns about limitations to access posed by the limited geographic availability of these treatments, their cost, and lack of insurance coverage. In addition, each stakeholder group cited lack of knowledge about PEIs as a perceived barrier to their wider implementation in depression care.
Our participants recognized there are significant geographic limitations to accessing PEIs, as many of these treatments are available only in large, well-resourced cities. This is especially true for DBS and ABIs as they remain investigational, require neurosurgery, and currently are offered only during clinical research trials. However, even for established therapies like ECT and rTMS, access often remains limited to larger treatment centers. Further, training on the proper implementation and use of these modalities is limited in the United States. Current requirements from the Accreditation Council for Graduate Medical Education state only that psychiatry residents demonstrate knowledge of these therapies and their indications, falling short of requiring first-hand experience in referring or administering them.2
Our participants also perceived the cost of these therapies as a significant barrier affecting a large proportion of patients who could potentially benefit from them. Another frequently mentioned barrier is the lack of insurance coverage for existing PEIs, particularly rTMS. Even when insurance covers treatment with an approved PEI (for example, ECT, rTMS), there may be a requirement to have tried and failed multiple antidepressant medications first. These insurance requirements may contribute to a lack of general clarity about when these treatments should be used. The psychiatrists we interviewed, for example, were almost evenly split between believing that ECT and/or rTMS should be offered earlier in the course of therapy and believing that they should be reserved only for patients with treatment-resistant depression.
Further, some psychiatrists we interviewed stated that they wanted more information about the appropriate use of these treatments. This is unsurprising, as the available guidelines for the approved electroceutical treatments are outdated. Although the American Psychiatric Association Task Force is due to publish updated guidelines for ECT, it has been more than 20 years since the current guidelines were published.3 More recent guidelines, such as those issued in 2016 by the Canadian Network for Mood and Anxiety Treatments cite studies that were even then several years old.4 For rTMS, newer guidelines are available, but they have not yet been revised to include recent developments such as the SAINT protocol.5,6
While useful, clinical guidelines do not provide all of the information psychiatrists require for clinical decision-making. They are only as good as the evidence available and to the extent that they include all of the considerations important to psychiatrists and the specific patients they are treating.7,8 We asked the psychiatrists in our interviews what practical information they would like to see included in treatment guidelines. They offered a range of suggestions: better guidance about which patients would be most likely to benefit, when to offer the treatments, and how to combine these therapies with other interventions.
For the experimental PEIs (DBS and ABIs), similar questions and concerns arise. In the current research context, psychiatrists may not be aware of which patients are good candidates for referral to clinical trials. If these therapies are approved, similar questions about patient selection and place in treatment (for example, first line, second line, etc.) remain.9
Finally, each of our participant groups believed that patients and the public lack adequate knowledge about electroceutical interventions, and they emphasized the importance of giving potential patients sufficient information to enable them to provide valid informed consent. This is important in the case of the approved electroceutical therapies (ECT and rTMS), in part because of the potential for decision-making to be influenced unduly by misinformation and controversy – especially given that the media’s depiction of these interventions might influence patients’ willingness to receive helpful therapies such as ECT.10
Our interviews were used to inform the development of a national survey of these four stakeholder groups, which will provide further information about perceived barriers to accessing PEIs.
Dr. Bluhm is associate professor of philosophy at Michigan State University, East Lansing. Dr. Achtyes is director of the division of psychiatry and behavioral medicine at Michigan State University, Grand Rapids. Dr. McCright is chair of the department of sociology at Michigan State University. Dr. Cabrera is Dorothy Foehr Huck and J. Lloyd Huck Chair in Neuroethics at the Huck Institutes of the Life Sciences, Penn State University, University Park.
References
1. Cabrera LY et al. Psychiatry Res. 2022 Jul;313:114612. doi: 10.1016/j.psychres.2022.114612.
2. Accreditation Council for Graduate Medical Education. Psychiatry – Program Requirements and FAQs. https://www.acgme.org/specialties/psychiatry/program-requirements-and-faqs-and-applications/
3. American Psychiatric Association. The Practice of Electroconvulsive Therapy, Second Edition: Recommendations for Treatment, Training, and Privileging. 2001.
4. Miley RV et al. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033.
5. Perera T et al. Brain Stimul. 2016 May-Jun;9(3):336-46. doi: 10.1016/j.brs.2016.03.010.
6. Cole EJ et al. Am J Psychiatry. 2020 Aug 1;177(8):716-26. doi: 10.1176/appi.ajp.2019.19070720.
7. Gabriel FC et al. PLoS One. 2020 Apr 21;15(4):e0231700. doi: 10.1371/journal.pone.0231700.
8. Woolf SH et al. BMJ. 1999 Feb 20;318(7182):527-30. doi: 10.1136/bmj.318.7182.527.
9. Widge AS et al. Biol Psychiatry. 2016 Feb 15;79(4):e9-10. doi: 10.1016/j.biopsych.2015.06.005.
10. Sienaert P. Brain Stimul. 2016 Nov-Dec;9(6):882-91. doi: 10.1016/j.brs.2016.07.005.
Psychiatric electroceutical interventions (PEIs) – including Food and Drug Administration–approved therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), as well as experimental interventions such as deep brain stimulation (DBS) and adaptive brain implants (ABI) – offer therapeutic promise for patients suffering with major depressive disorder (MDD). Yet there remain many open questions regarding their use, even in cases where their safety and effectiveness is well established.
Our research aims to better understand how different stakeholder groups view these interventions. We conducted a series of interviews with psychiatrists, patients with MDD, and members of the public to more fully comprehend these groups’ perceptions of barriers to using these therapies.1 They raised concerns about limitations to access posed by the limited geographic availability of these treatments, their cost, and lack of insurance coverage. In addition, each stakeholder group cited lack of knowledge about PEIs as a perceived barrier to their wider implementation in depression care.
Our participants recognized there are significant geographic limitations to accessing PEIs, as many of these treatments are available only in large, well-resourced cities. This is especially true for DBS and ABIs as they remain investigational, require neurosurgery, and currently are offered only during clinical research trials. However, even for established therapies like ECT and rTMS, access often remains limited to larger treatment centers. Further, training on the proper implementation and use of these modalities is limited in the United States. Current requirements from the Accreditation Council for Graduate Medical Education state only that psychiatry residents demonstrate knowledge of these therapies and their indications, falling short of requiring first-hand experience in referring or administering them.2
Our participants also perceived the cost of these therapies as a significant barrier affecting a large proportion of patients who could potentially benefit from them. Another frequently mentioned barrier is the lack of insurance coverage for existing PEIs, particularly rTMS. Even when insurance covers treatment with an approved PEI (for example, ECT, rTMS), there may be a requirement to have tried and failed multiple antidepressant medications first. These insurance requirements may contribute to a lack of general clarity about when these treatments should be used. The psychiatrists we interviewed, for example, were almost evenly split between believing that ECT and/or rTMS should be offered earlier in the course of therapy and believing that they should be reserved only for patients with treatment-resistant depression.
Further, some psychiatrists we interviewed stated that they wanted more information about the appropriate use of these treatments. This is unsurprising, as the available guidelines for the approved electroceutical treatments are outdated. Although the American Psychiatric Association Task Force is due to publish updated guidelines for ECT, it has been more than 20 years since the current guidelines were published.3 More recent guidelines, such as those issued in 2016 by the Canadian Network for Mood and Anxiety Treatments cite studies that were even then several years old.4 For rTMS, newer guidelines are available, but they have not yet been revised to include recent developments such as the SAINT protocol.5,6
While useful, clinical guidelines do not provide all of the information psychiatrists require for clinical decision-making. They are only as good as the evidence available and to the extent that they include all of the considerations important to psychiatrists and the specific patients they are treating.7,8 We asked the psychiatrists in our interviews what practical information they would like to see included in treatment guidelines. They offered a range of suggestions: better guidance about which patients would be most likely to benefit, when to offer the treatments, and how to combine these therapies with other interventions.
For the experimental PEIs (DBS and ABIs), similar questions and concerns arise. In the current research context, psychiatrists may not be aware of which patients are good candidates for referral to clinical trials. If these therapies are approved, similar questions about patient selection and place in treatment (for example, first line, second line, etc.) remain.9
Finally, each of our participant groups believed that patients and the public lack adequate knowledge about electroceutical interventions, and they emphasized the importance of giving potential patients sufficient information to enable them to provide valid informed consent. This is important in the case of the approved electroceutical therapies (ECT and rTMS), in part because of the potential for decision-making to be influenced unduly by misinformation and controversy – especially given that the media’s depiction of these interventions might influence patients’ willingness to receive helpful therapies such as ECT.10
Our interviews were used to inform the development of a national survey of these four stakeholder groups, which will provide further information about perceived barriers to accessing PEIs.
Dr. Bluhm is associate professor of philosophy at Michigan State University, East Lansing. Dr. Achtyes is director of the division of psychiatry and behavioral medicine at Michigan State University, Grand Rapids. Dr. McCright is chair of the department of sociology at Michigan State University. Dr. Cabrera is Dorothy Foehr Huck and J. Lloyd Huck Chair in Neuroethics at the Huck Institutes of the Life Sciences, Penn State University, University Park.
References
1. Cabrera LY et al. Psychiatry Res. 2022 Jul;313:114612. doi: 10.1016/j.psychres.2022.114612.
2. Accreditation Council for Graduate Medical Education. Psychiatry – Program Requirements and FAQs. https://www.acgme.org/specialties/psychiatry/program-requirements-and-faqs-and-applications/
3. American Psychiatric Association. The Practice of Electroconvulsive Therapy, Second Edition: Recommendations for Treatment, Training, and Privileging. 2001.
4. Miley RV et al. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033.
5. Perera T et al. Brain Stimul. 2016 May-Jun;9(3):336-46. doi: 10.1016/j.brs.2016.03.010.
6. Cole EJ et al. Am J Psychiatry. 2020 Aug 1;177(8):716-26. doi: 10.1176/appi.ajp.2019.19070720.
7. Gabriel FC et al. PLoS One. 2020 Apr 21;15(4):e0231700. doi: 10.1371/journal.pone.0231700.
8. Woolf SH et al. BMJ. 1999 Feb 20;318(7182):527-30. doi: 10.1136/bmj.318.7182.527.
9. Widge AS et al. Biol Psychiatry. 2016 Feb 15;79(4):e9-10. doi: 10.1016/j.biopsych.2015.06.005.
10. Sienaert P. Brain Stimul. 2016 Nov-Dec;9(6):882-91. doi: 10.1016/j.brs.2016.07.005.
Psychiatric electroceutical interventions (PEIs) – including Food and Drug Administration–approved therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), as well as experimental interventions such as deep brain stimulation (DBS) and adaptive brain implants (ABI) – offer therapeutic promise for patients suffering with major depressive disorder (MDD). Yet there remain many open questions regarding their use, even in cases where their safety and effectiveness is well established.
Our research aims to better understand how different stakeholder groups view these interventions. We conducted a series of interviews with psychiatrists, patients with MDD, and members of the public to more fully comprehend these groups’ perceptions of barriers to using these therapies.1 They raised concerns about limitations to access posed by the limited geographic availability of these treatments, their cost, and lack of insurance coverage. In addition, each stakeholder group cited lack of knowledge about PEIs as a perceived barrier to their wider implementation in depression care.
Our participants recognized there are significant geographic limitations to accessing PEIs, as many of these treatments are available only in large, well-resourced cities. This is especially true for DBS and ABIs as they remain investigational, require neurosurgery, and currently are offered only during clinical research trials. However, even for established therapies like ECT and rTMS, access often remains limited to larger treatment centers. Further, training on the proper implementation and use of these modalities is limited in the United States. Current requirements from the Accreditation Council for Graduate Medical Education state only that psychiatry residents demonstrate knowledge of these therapies and their indications, falling short of requiring first-hand experience in referring or administering them.2
Our participants also perceived the cost of these therapies as a significant barrier affecting a large proportion of patients who could potentially benefit from them. Another frequently mentioned barrier is the lack of insurance coverage for existing PEIs, particularly rTMS. Even when insurance covers treatment with an approved PEI (for example, ECT, rTMS), there may be a requirement to have tried and failed multiple antidepressant medications first. These insurance requirements may contribute to a lack of general clarity about when these treatments should be used. The psychiatrists we interviewed, for example, were almost evenly split between believing that ECT and/or rTMS should be offered earlier in the course of therapy and believing that they should be reserved only for patients with treatment-resistant depression.
Further, some psychiatrists we interviewed stated that they wanted more information about the appropriate use of these treatments. This is unsurprising, as the available guidelines for the approved electroceutical treatments are outdated. Although the American Psychiatric Association Task Force is due to publish updated guidelines for ECT, it has been more than 20 years since the current guidelines were published.3 More recent guidelines, such as those issued in 2016 by the Canadian Network for Mood and Anxiety Treatments cite studies that were even then several years old.4 For rTMS, newer guidelines are available, but they have not yet been revised to include recent developments such as the SAINT protocol.5,6
While useful, clinical guidelines do not provide all of the information psychiatrists require for clinical decision-making. They are only as good as the evidence available and to the extent that they include all of the considerations important to psychiatrists and the specific patients they are treating.7,8 We asked the psychiatrists in our interviews what practical information they would like to see included in treatment guidelines. They offered a range of suggestions: better guidance about which patients would be most likely to benefit, when to offer the treatments, and how to combine these therapies with other interventions.
For the experimental PEIs (DBS and ABIs), similar questions and concerns arise. In the current research context, psychiatrists may not be aware of which patients are good candidates for referral to clinical trials. If these therapies are approved, similar questions about patient selection and place in treatment (for example, first line, second line, etc.) remain.9
Finally, each of our participant groups believed that patients and the public lack adequate knowledge about electroceutical interventions, and they emphasized the importance of giving potential patients sufficient information to enable them to provide valid informed consent. This is important in the case of the approved electroceutical therapies (ECT and rTMS), in part because of the potential for decision-making to be influenced unduly by misinformation and controversy – especially given that the media’s depiction of these interventions might influence patients’ willingness to receive helpful therapies such as ECT.10
Our interviews were used to inform the development of a national survey of these four stakeholder groups, which will provide further information about perceived barriers to accessing PEIs.
Dr. Bluhm is associate professor of philosophy at Michigan State University, East Lansing. Dr. Achtyes is director of the division of psychiatry and behavioral medicine at Michigan State University, Grand Rapids. Dr. McCright is chair of the department of sociology at Michigan State University. Dr. Cabrera is Dorothy Foehr Huck and J. Lloyd Huck Chair in Neuroethics at the Huck Institutes of the Life Sciences, Penn State University, University Park.
References
1. Cabrera LY et al. Psychiatry Res. 2022 Jul;313:114612. doi: 10.1016/j.psychres.2022.114612.
2. Accreditation Council for Graduate Medical Education. Psychiatry – Program Requirements and FAQs. https://www.acgme.org/specialties/psychiatry/program-requirements-and-faqs-and-applications/
3. American Psychiatric Association. The Practice of Electroconvulsive Therapy, Second Edition: Recommendations for Treatment, Training, and Privileging. 2001.
4. Miley RV et al. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033.
5. Perera T et al. Brain Stimul. 2016 May-Jun;9(3):336-46. doi: 10.1016/j.brs.2016.03.010.
6. Cole EJ et al. Am J Psychiatry. 2020 Aug 1;177(8):716-26. doi: 10.1176/appi.ajp.2019.19070720.
7. Gabriel FC et al. PLoS One. 2020 Apr 21;15(4):e0231700. doi: 10.1371/journal.pone.0231700.
8. Woolf SH et al. BMJ. 1999 Feb 20;318(7182):527-30. doi: 10.1136/bmj.318.7182.527.
9. Widge AS et al. Biol Psychiatry. 2016 Feb 15;79(4):e9-10. doi: 10.1016/j.biopsych.2015.06.005.
10. Sienaert P. Brain Stimul. 2016 Nov-Dec;9(6):882-91. doi: 10.1016/j.brs.2016.07.005.
Janus Kinase Inhibitors: A Promising Therapeutic Option for Allergic Contact Dermatitis
Allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction that usually manifests with eczematous lesions within hours to days after exposure to a contact allergen. The primary treatment of ACD consists of allergen avoidance, but medications also may be necessary to manage symptoms, particularly in cases where avoidance alone does not lead to resolution of dermatitis. At present, no medical therapies are explicitly approved for use in the management of ACD. Janus kinase (JAK) inhibitors are a class of small molecule inhibitors that are used for the treatment of a range of inflammatory diseases, such as rheumatoid arthritis and psoriatic arthritis. Several oral and topical JAK inhibitors also have recently been approved by the US Food and Drug Administration (FDA) for atopic dermatitis (AD). In this article, we discuss this important class of medications and the role that they may play in the off-label management of refractory ACD.
JAK/STAT Signaling Pathway
The JAK/signal transducer and activator of transcription (STAT) pathway plays a crucial role in many biologic processes. Notably, JAK/STAT signaling is involved in the development and regulation of the immune system.1 The cascade begins when a particular transmembrane receptor binds a ligand, such as an interferon or interleukin.2 Upon ligand binding, the receptor dimerizes or oligomerizes, bringing the relevant JAK proteins into close approximation to each other.3 This allows the JAK proteins to autophosphorylate or transphosphorylate.2-4 Phosphorylation activates the JAK proteins and increases their kinase activity.3 In humans, there are 4 JAK proteins: JAK1, JAK2, JAK3, and tyrosine kinase 2.4 When activated, the JAK proteins phosphorylate specific tyrosine residues on the receptor, which creates a docking site for STAT proteins. After binding, the STAT proteins then are phosphorylated, leading to their dimerization and translocation to the nucleus.2,3 Once in the nucleus, the STAT proteins act as transcription factors for target genes.3
JAK Inhibitors
Janus kinase inhibitors are immunomodulatory medications that work through inhibition of 1 or more of the JAK proteins in the JAK/STAT pathway. Through this mechanism, JAK inhibitors can impede the activity of proinflammatory cytokines and T cells.4 A brief overview of the commercially available JAK inhibitors in Europe, Japan, and the United States is provided in the Table.5-29
Of the approved JAK inhibitors, more than 40% are indicated for AD. The first JAK inhibitor to be approved in the topical form was delgocitinib in 2020 in Japan.5 In a phase 3 trial, delgocitinib demonstrated significant reductions in modified Eczema Area and Severity Index (EASI) score (P<.001) as well as Peak Pruritus Numerical Rating Scale (P<.001) when compared with vehicle.30 Topical ruxolitinib soon followed when its approval for AD was announced by the FDA in 2021.31 Results from 2 phase 3 trials found that significantly more patients achieved investigator global assessment (IGA) treatment success (P<.0001) and a significant reduction in itch as measured by the Peak Pruritus Numerical Rating Scale (P<.001) with topical ruxolitinib vs vehicle.32
The first oral JAK inhibitor to attain approval for AD was baricitinib in Europe and Japan, but it is not currently approved for this indication in the United States by the FDA.11,12,33 Consistent findings across phase 3 trials revealed that baricitinib was more effective at achieving IGA treatment success and improved EASI scores compared with placebo.33
Upadacitinib, another oral JAK inhibitor, was subsequently approved for AD in Europe and Japan in 2021 and in the United States in early 2022.5,9,26,27 Two replicate phase 3 trials demonstrated significant improvement in EASI score, itch, and quality of life with upadacitinib compared with placebo (P<.0001).34 Abrocitinib was granted FDA approval for AD in the same time period, with phase 3 trials exhibiting greater responses in IGA and EASI scores vs placebo.35
Potential for Use in ACD
Given the successful use of JAK inhibitors in the management of AD, there is optimism that these medications also may have potential application in ACD. Recent literature suggests that the 2 conditions may be more closely related mechanistically than previously understood. As a result, AD and ACD often are managed with the same therapeutic agents.36
Although the exact etiology of ACD is still being elucidated, activation of T cells and cytokines plays an important role.37 Notably, more than 40 cytokines exert their effects through the JAK/STAT signaling pathway, including IL-2, IL-6, IL-17, IL-22, and IFN-γ.37,38 A study on nickel contact allergy revealed that JAK/STAT activation may regulate the balance between IL-12 and IL-23 and increase type 1 T-helper (TH1) polarization.39 Skin inflammation and chronic pruritus, which are major components of ACD, also are thought to be mediated in part by JAK signaling.34,40
Animal studies have suggested that JAK inhibitors may show benefit in the management of ACD. Rats with oxazolone-induced ACD were found to have less swelling and epidermal thickening in the area of induced dermatitis after treatment with oral tofacitinib, comparable to the effects of cyclosporine. Tofacitinib was presumed to exert its effects through cytokine suppression, particularly that of IFN-γ, IL-22, and tumor necrosis factor α.41 In a separate study on mice with toluene-2,4-diisocyanate–induced ACD, both tofacitinib and another JAK inhibitor, oclacitinib, demonstrated inhibition of cytokine production, migration, and maturation of bone marrow–derived dendritic cells. Both topical and oral formulations of these 2 JAK inhibitors also were found to decrease scratching behavior; only the topicals improved ear thickness (used as a marker of skin inflammation), suggesting potential benefits to local application.42 In a murine model, oral delgocitinib also attenuated contact hypersensitivity via inhibition of antigen-specific T-cell proliferation and cytokine production.37 Finally, in a randomized clinical trial conducted on dogs with allergic dermatitis (of which 10% were presumed to be from contact allergy), oral oclacitinib significantly reduced pruritus and clinical severity scores vs placebo (P<.0001).43
There also are early clinical studies and case reports highlighting the effective use of JAK inhibitors in the management of ACD in humans. A 37-year-old man with occupational airborne ACD to Compositae saw full clearance of his dermatitis with daily oral abrocitinib after topical corticosteroids and dupilumab failed.44 Another patient, a 57-year-old woman, had near-complete resolution of chronic Parthenium-induced airborne ACD after starting twice-daily oral tofacitinib. Allergen avoidance, as well as multiple medications, including topical and oral corticosteroids, topical calcineurin inhibitors, and azathioprine, previously failed in this patient.45 Finally, a phase 2 study on patients with irritant and nonirritant chronic hand eczema found that significantly more patients achieved treatment success (as measured by the physician global assessment) with topical delgocitinib vs vehicle (P=.009).46 Chronic hand eczema may be due to a variety of causes, including AD, irritant contact dermatitis, and ACD. Thus, these studies begin to highlight the potential role for JAK inhibitors in the management of refractory ACD.
Side Effects of JAK Inhibitors
The safety profile of JAK inhibitors must be taken into consideration. In general, topical JAK inhibitors are safe and well tolerated, with the majority of adverse events (AEs) seen in clinical trials considered mild or unrelated to the medication.30,32 Nasopharyngitis, local skin infection, and acne were reported; a systematic review found no increased risk of AEs with topical JAK inhibitors compared with placebo.30,32,47 Application-site reactions, a common concern among the existing topical calcineurin and phosphodiesterase 4 inhibitors, were rare (approximately 2% of patients).47 The most frequent AEs seen in clinical trials of oral JAK inhibitors included acne, nasopharyngitis/upper respiratory tract infections, nausea, and headache.33-35 Herpes simplex virus infection and worsening of AD also were seen. Although elevations in creatine phosphokinase levels were reported, patients often were asymptomatic and elevations were related to exercise or resolved without treatment interruption.33-35
As a class, JAK inhibitors carry a boxed warning for serious infections, malignancy, major adverse cardiovascular events, thrombosis, and mortality. The FDA placed this label on JAK inhibitors because of the results of a randomized controlled trial of oral tofacitinib vs tumor necrosis factor α inhibitors in RA.48,49 Notably, participants in the trial had to be 50 years or older and have at least 1 additional cardiovascular risk factor. Postmarket safety data are still being collected for patients with AD and other dermatologic conditions, but the findings of safety analyses have been reassuring to date.50,51 Regular follow-up and routine laboratory monitoring are recommended for any patient started on an oral JAK inhibitor, which often includes monitoring of the complete blood cell count, comprehensive metabolic panel, and lipids, as well as baseline screening for tuberculosis and hepatitis.52,53 For topical JAK inhibitors, no specific laboratory monitoring is recommended.
Finally, it must be considered that the challenges of off-label prescribing combined with high costs may limit access to JAK inhibitors for use in ACD.
Final Interpretation
Early investigations, including studies on animals and humans, suggest that JAK inhibitors are a promising option in the management of treatment-refractory ACD. Patients and providers should be aware of both the benefits and known side effects of JAK inhibitors prior to treatment initiation.
- Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228:273-287.
- Bousoik E, Montazeri Aliabadi H. “Do we know Jack” about JAK? a closer look at JAK/STAT signaling pathway. Front Oncol. 2018;8:287.
- Jatiani SS, Baker SJ, Silverman LR, et al. Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer. 2010;1:979-993.
- Seif F, Khoshmirsafa M, Aazami H, et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017;15:23.
- Traidl S, Freimooser S, Werfel T. Janus kinase inhibitors for the therapy of atopic dermatitis. Allergol Select. 2021;5:293-304.
- Opzelura (ruxolitinib) cream. Prescribing information. Incyte Corporation; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215309s001lbl.pdf
- Cibinqo (abrocitinib) tablets. Prescribing information. Pfizer Labs; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213871s000lbl.pdf
- Cibinqo. Product information. European Medicines Agency. Published December 17, 2021. Updated November 10, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/cibinqo
- New drugs approved in FY 2021. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000246734.pdf
- Olumiant (baricitinib) tablets. Prescribing information. Eli Lilly and Company; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s007lbl.pdf
- Olumiant. Product information. European Medicines Agency. Published March 16, 2017. Updated June 29, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant
- Review report: Olumiant. Pharmaceuticals and Medical Devices Agency. April 21, 2021. Accessed January 20, 2023. https://www.pmda.go.jp/files/000243207.pdf
- Sotyktu (deucravacitinib) tablets. Prescribing information. Bristol-Myers Squibb Company; 2022. Accessed January 20, 2023.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214958s000lbl.pdf
- Inrebic (fedratinib) capsules. Prescribing information. Celgene Corporation; 2019. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf
- Inrebic. Product information. European Medicines Agency. Published March 3, 2021. Updated December 8, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/inrebic
- Jyseleca. Product information. European Medicines Agency. Published September 28, 2020. Updated November 9, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/documents/product-information/jyseleca-epar-product-information_en.pdf
- Review report: Jyseleca. Pharmaceuticals and Medical Devices Agency. September 8, 2020. Accessed January 20, 2023. https://www.pmda.go.jp/files/000247830.pdf
- Vonjo (pacritinib) capsules. Prescribing information. CTI BioPharma Corp; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208712s000lbl.pdf
- Review report: Smyraf. Pharmaceuticals and Medical Devices Agency. February 28, 2019. Accessed January 20, 2023. https://www.pmda.go.jp/files/000233074.pdf
- Jakafi (ruxolitinib) tablets. Prescribing information. Incyte Corporation; 2021. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202192s023lbl.pdf
- Jakavi. Product information. European Medicines Agency. Published October 4, 2012. Updated May 18, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/jakavi
- New drugs approved in FY 2014. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000229076.pdf
- Xeljanz (tofacitinib). Prescribing information. Pfizer Labs; 2021. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/203214s028,208246s013,213082s003lbl.pdf
- Xeljanz. Product information. European Medicines Agency. Accessed January 20, 2023. https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf
- Review report: Xeljanz. Pharmaceuticals and Medical Devices Agency. January 20, 2023. https://www.pmda.go.jp/files/000237584.pdf
- Rinvoq (upadacitinib) extended-release tablets. Prescribing information. AbbVie Inc; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211675s003lbl.pdf
- Rinvoq. Product information. European Medicines Agency. Published December 18, 2019. Updated December 7, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq
- New drugs approved in FY 2019. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000235289.pdfs
- New drugs approved in May 2022. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000248626.pdf
- Nakagawa H, Nemoto O, Igarashi A, et al. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82:823-831. Erratum appears in J Am Acad Dermatol. 2021;85:1069.
- Sideris N, Paschou E, Bakirtzi K, et al. New and upcoming topical treatments for atopic dermatitis: a review of the literature. J Clin Med. 2022;11:4974.
- Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85:863-872.
- Radi G, Simonetti O, Rizzetto G, et al. Baricitinib: the first Jak inhibitor approved in Europe for the treatment of moderate to severe atopic dermatitis in adult patients. Healthcare (Basel). 2021;9:1575.
- Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021;397:2151-2168. Erratum appears in Lancet. 2021;397:2150.
- Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384:1101-1112.
- Johnson H, Novack DE, Adler BL, et al. Can atopic dermatitis and allergic contact dermatitis coexist? Cutis. 2022;110:139-142.
- Amano W, Nakajima S, Yamamoto Y, et al. JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation. J Dermatol Sci. 2016;84:258-265.
- O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-328.
- Bechara R, Antonios D, Azouri H, et al. Nickel sulfate promotes IL-17A producing CD4+ T cells by an IL-23-dependent mechanism regulated by TLR4 and JAK-STAT pathways. J Invest Dermatol. 2017;137:2140-2148.
- Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171:217-228.e13.
- Fujii Y, Sengoku T. Effects of the Janus kinase inhibitor CP-690550 (tofacitinib) in a rat model of oxazolone-induced chronic dermatitis. Pharmacology. 2013;91:207-213.
- Fukuyama T, Ehling S, Cook E, et al. Topically administered Janus-kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis. J Pharmacol Exp Ther. 2015;354:394-405.
- Cosgrove SB, Wren JA, Cleaver DM, et al. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol. 2013;24:479, E114.
- Baltazar D, Shinamoto SR, Hamann CP, et al. Occupational airborne allergic contact dermatitis to invasive Compositae species treated with abrocitinib: a case report. Contact Dermatitis. 2022;87:542-544.
- Muddebihal A, Sardana K, Sinha S, et al. Tofacitinib in refractory Parthenium-induced airborne allergic contact dermatitis [published online October 12, 2022]. Contact Dermatitis. doi:10.1111/cod.14234
- Worm M, Bauer A, Elsner P, et al. Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study. Br J Dermatol. 2020;182:1103-1110.
- Chen J, Cheng J, Yang H, et al. The efficacy and safety of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and meta-analysis. J Am Acad Dermatol. 2022;87:495-496.
- Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326.
- US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Updated December 7, 2021. Accessed January 20, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
- Chen TL, Lee LL, Huang HK, et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: a systematic review and meta-analysis. JAMA Dermatol. 2022;158:1254-1261.
- King B, Maari C, Lain E, et al. Extended safety analysis of baricitinib 2 mg in adult patients with atopic dermatitis: an integrated analysis from eight randomized clinical trials. Am J Clin Dermatol. 2021;22:395-405.
- Nash P, Kerschbaumer A, Dörner T, et al. Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis. 2021;80:71-87.
- Narla S, Silverberg JI. The suitability of treating atopic dermatitis with Janus kinase inhibitors. Exp Rev Clin Immunol. 2022;18:439-459.
Allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction that usually manifests with eczematous lesions within hours to days after exposure to a contact allergen. The primary treatment of ACD consists of allergen avoidance, but medications also may be necessary to manage symptoms, particularly in cases where avoidance alone does not lead to resolution of dermatitis. At present, no medical therapies are explicitly approved for use in the management of ACD. Janus kinase (JAK) inhibitors are a class of small molecule inhibitors that are used for the treatment of a range of inflammatory diseases, such as rheumatoid arthritis and psoriatic arthritis. Several oral and topical JAK inhibitors also have recently been approved by the US Food and Drug Administration (FDA) for atopic dermatitis (AD). In this article, we discuss this important class of medications and the role that they may play in the off-label management of refractory ACD.
JAK/STAT Signaling Pathway
The JAK/signal transducer and activator of transcription (STAT) pathway plays a crucial role in many biologic processes. Notably, JAK/STAT signaling is involved in the development and regulation of the immune system.1 The cascade begins when a particular transmembrane receptor binds a ligand, such as an interferon or interleukin.2 Upon ligand binding, the receptor dimerizes or oligomerizes, bringing the relevant JAK proteins into close approximation to each other.3 This allows the JAK proteins to autophosphorylate or transphosphorylate.2-4 Phosphorylation activates the JAK proteins and increases their kinase activity.3 In humans, there are 4 JAK proteins: JAK1, JAK2, JAK3, and tyrosine kinase 2.4 When activated, the JAK proteins phosphorylate specific tyrosine residues on the receptor, which creates a docking site for STAT proteins. After binding, the STAT proteins then are phosphorylated, leading to their dimerization and translocation to the nucleus.2,3 Once in the nucleus, the STAT proteins act as transcription factors for target genes.3
JAK Inhibitors
Janus kinase inhibitors are immunomodulatory medications that work through inhibition of 1 or more of the JAK proteins in the JAK/STAT pathway. Through this mechanism, JAK inhibitors can impede the activity of proinflammatory cytokines and T cells.4 A brief overview of the commercially available JAK inhibitors in Europe, Japan, and the United States is provided in the Table.5-29
Of the approved JAK inhibitors, more than 40% are indicated for AD. The first JAK inhibitor to be approved in the topical form was delgocitinib in 2020 in Japan.5 In a phase 3 trial, delgocitinib demonstrated significant reductions in modified Eczema Area and Severity Index (EASI) score (P<.001) as well as Peak Pruritus Numerical Rating Scale (P<.001) when compared with vehicle.30 Topical ruxolitinib soon followed when its approval for AD was announced by the FDA in 2021.31 Results from 2 phase 3 trials found that significantly more patients achieved investigator global assessment (IGA) treatment success (P<.0001) and a significant reduction in itch as measured by the Peak Pruritus Numerical Rating Scale (P<.001) with topical ruxolitinib vs vehicle.32
The first oral JAK inhibitor to attain approval for AD was baricitinib in Europe and Japan, but it is not currently approved for this indication in the United States by the FDA.11,12,33 Consistent findings across phase 3 trials revealed that baricitinib was more effective at achieving IGA treatment success and improved EASI scores compared with placebo.33
Upadacitinib, another oral JAK inhibitor, was subsequently approved for AD in Europe and Japan in 2021 and in the United States in early 2022.5,9,26,27 Two replicate phase 3 trials demonstrated significant improvement in EASI score, itch, and quality of life with upadacitinib compared with placebo (P<.0001).34 Abrocitinib was granted FDA approval for AD in the same time period, with phase 3 trials exhibiting greater responses in IGA and EASI scores vs placebo.35
Potential for Use in ACD
Given the successful use of JAK inhibitors in the management of AD, there is optimism that these medications also may have potential application in ACD. Recent literature suggests that the 2 conditions may be more closely related mechanistically than previously understood. As a result, AD and ACD often are managed with the same therapeutic agents.36
Although the exact etiology of ACD is still being elucidated, activation of T cells and cytokines plays an important role.37 Notably, more than 40 cytokines exert their effects through the JAK/STAT signaling pathway, including IL-2, IL-6, IL-17, IL-22, and IFN-γ.37,38 A study on nickel contact allergy revealed that JAK/STAT activation may regulate the balance between IL-12 and IL-23 and increase type 1 T-helper (TH1) polarization.39 Skin inflammation and chronic pruritus, which are major components of ACD, also are thought to be mediated in part by JAK signaling.34,40
Animal studies have suggested that JAK inhibitors may show benefit in the management of ACD. Rats with oxazolone-induced ACD were found to have less swelling and epidermal thickening in the area of induced dermatitis after treatment with oral tofacitinib, comparable to the effects of cyclosporine. Tofacitinib was presumed to exert its effects through cytokine suppression, particularly that of IFN-γ, IL-22, and tumor necrosis factor α.41 In a separate study on mice with toluene-2,4-diisocyanate–induced ACD, both tofacitinib and another JAK inhibitor, oclacitinib, demonstrated inhibition of cytokine production, migration, and maturation of bone marrow–derived dendritic cells. Both topical and oral formulations of these 2 JAK inhibitors also were found to decrease scratching behavior; only the topicals improved ear thickness (used as a marker of skin inflammation), suggesting potential benefits to local application.42 In a murine model, oral delgocitinib also attenuated contact hypersensitivity via inhibition of antigen-specific T-cell proliferation and cytokine production.37 Finally, in a randomized clinical trial conducted on dogs with allergic dermatitis (of which 10% were presumed to be from contact allergy), oral oclacitinib significantly reduced pruritus and clinical severity scores vs placebo (P<.0001).43
There also are early clinical studies and case reports highlighting the effective use of JAK inhibitors in the management of ACD in humans. A 37-year-old man with occupational airborne ACD to Compositae saw full clearance of his dermatitis with daily oral abrocitinib after topical corticosteroids and dupilumab failed.44 Another patient, a 57-year-old woman, had near-complete resolution of chronic Parthenium-induced airborne ACD after starting twice-daily oral tofacitinib. Allergen avoidance, as well as multiple medications, including topical and oral corticosteroids, topical calcineurin inhibitors, and azathioprine, previously failed in this patient.45 Finally, a phase 2 study on patients with irritant and nonirritant chronic hand eczema found that significantly more patients achieved treatment success (as measured by the physician global assessment) with topical delgocitinib vs vehicle (P=.009).46 Chronic hand eczema may be due to a variety of causes, including AD, irritant contact dermatitis, and ACD. Thus, these studies begin to highlight the potential role for JAK inhibitors in the management of refractory ACD.
Side Effects of JAK Inhibitors
The safety profile of JAK inhibitors must be taken into consideration. In general, topical JAK inhibitors are safe and well tolerated, with the majority of adverse events (AEs) seen in clinical trials considered mild or unrelated to the medication.30,32 Nasopharyngitis, local skin infection, and acne were reported; a systematic review found no increased risk of AEs with topical JAK inhibitors compared with placebo.30,32,47 Application-site reactions, a common concern among the existing topical calcineurin and phosphodiesterase 4 inhibitors, were rare (approximately 2% of patients).47 The most frequent AEs seen in clinical trials of oral JAK inhibitors included acne, nasopharyngitis/upper respiratory tract infections, nausea, and headache.33-35 Herpes simplex virus infection and worsening of AD also were seen. Although elevations in creatine phosphokinase levels were reported, patients often were asymptomatic and elevations were related to exercise or resolved without treatment interruption.33-35
As a class, JAK inhibitors carry a boxed warning for serious infections, malignancy, major adverse cardiovascular events, thrombosis, and mortality. The FDA placed this label on JAK inhibitors because of the results of a randomized controlled trial of oral tofacitinib vs tumor necrosis factor α inhibitors in RA.48,49 Notably, participants in the trial had to be 50 years or older and have at least 1 additional cardiovascular risk factor. Postmarket safety data are still being collected for patients with AD and other dermatologic conditions, but the findings of safety analyses have been reassuring to date.50,51 Regular follow-up and routine laboratory monitoring are recommended for any patient started on an oral JAK inhibitor, which often includes monitoring of the complete blood cell count, comprehensive metabolic panel, and lipids, as well as baseline screening for tuberculosis and hepatitis.52,53 For topical JAK inhibitors, no specific laboratory monitoring is recommended.
Finally, it must be considered that the challenges of off-label prescribing combined with high costs may limit access to JAK inhibitors for use in ACD.
Final Interpretation
Early investigations, including studies on animals and humans, suggest that JAK inhibitors are a promising option in the management of treatment-refractory ACD. Patients and providers should be aware of both the benefits and known side effects of JAK inhibitors prior to treatment initiation.
Allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction that usually manifests with eczematous lesions within hours to days after exposure to a contact allergen. The primary treatment of ACD consists of allergen avoidance, but medications also may be necessary to manage symptoms, particularly in cases where avoidance alone does not lead to resolution of dermatitis. At present, no medical therapies are explicitly approved for use in the management of ACD. Janus kinase (JAK) inhibitors are a class of small molecule inhibitors that are used for the treatment of a range of inflammatory diseases, such as rheumatoid arthritis and psoriatic arthritis. Several oral and topical JAK inhibitors also have recently been approved by the US Food and Drug Administration (FDA) for atopic dermatitis (AD). In this article, we discuss this important class of medications and the role that they may play in the off-label management of refractory ACD.
JAK/STAT Signaling Pathway
The JAK/signal transducer and activator of transcription (STAT) pathway plays a crucial role in many biologic processes. Notably, JAK/STAT signaling is involved in the development and regulation of the immune system.1 The cascade begins when a particular transmembrane receptor binds a ligand, such as an interferon or interleukin.2 Upon ligand binding, the receptor dimerizes or oligomerizes, bringing the relevant JAK proteins into close approximation to each other.3 This allows the JAK proteins to autophosphorylate or transphosphorylate.2-4 Phosphorylation activates the JAK proteins and increases their kinase activity.3 In humans, there are 4 JAK proteins: JAK1, JAK2, JAK3, and tyrosine kinase 2.4 When activated, the JAK proteins phosphorylate specific tyrosine residues on the receptor, which creates a docking site for STAT proteins. After binding, the STAT proteins then are phosphorylated, leading to their dimerization and translocation to the nucleus.2,3 Once in the nucleus, the STAT proteins act as transcription factors for target genes.3
JAK Inhibitors
Janus kinase inhibitors are immunomodulatory medications that work through inhibition of 1 or more of the JAK proteins in the JAK/STAT pathway. Through this mechanism, JAK inhibitors can impede the activity of proinflammatory cytokines and T cells.4 A brief overview of the commercially available JAK inhibitors in Europe, Japan, and the United States is provided in the Table.5-29
Of the approved JAK inhibitors, more than 40% are indicated for AD. The first JAK inhibitor to be approved in the topical form was delgocitinib in 2020 in Japan.5 In a phase 3 trial, delgocitinib demonstrated significant reductions in modified Eczema Area and Severity Index (EASI) score (P<.001) as well as Peak Pruritus Numerical Rating Scale (P<.001) when compared with vehicle.30 Topical ruxolitinib soon followed when its approval for AD was announced by the FDA in 2021.31 Results from 2 phase 3 trials found that significantly more patients achieved investigator global assessment (IGA) treatment success (P<.0001) and a significant reduction in itch as measured by the Peak Pruritus Numerical Rating Scale (P<.001) with topical ruxolitinib vs vehicle.32
The first oral JAK inhibitor to attain approval for AD was baricitinib in Europe and Japan, but it is not currently approved for this indication in the United States by the FDA.11,12,33 Consistent findings across phase 3 trials revealed that baricitinib was more effective at achieving IGA treatment success and improved EASI scores compared with placebo.33
Upadacitinib, another oral JAK inhibitor, was subsequently approved for AD in Europe and Japan in 2021 and in the United States in early 2022.5,9,26,27 Two replicate phase 3 trials demonstrated significant improvement in EASI score, itch, and quality of life with upadacitinib compared with placebo (P<.0001).34 Abrocitinib was granted FDA approval for AD in the same time period, with phase 3 trials exhibiting greater responses in IGA and EASI scores vs placebo.35
Potential for Use in ACD
Given the successful use of JAK inhibitors in the management of AD, there is optimism that these medications also may have potential application in ACD. Recent literature suggests that the 2 conditions may be more closely related mechanistically than previously understood. As a result, AD and ACD often are managed with the same therapeutic agents.36
Although the exact etiology of ACD is still being elucidated, activation of T cells and cytokines plays an important role.37 Notably, more than 40 cytokines exert their effects through the JAK/STAT signaling pathway, including IL-2, IL-6, IL-17, IL-22, and IFN-γ.37,38 A study on nickel contact allergy revealed that JAK/STAT activation may regulate the balance between IL-12 and IL-23 and increase type 1 T-helper (TH1) polarization.39 Skin inflammation and chronic pruritus, which are major components of ACD, also are thought to be mediated in part by JAK signaling.34,40
Animal studies have suggested that JAK inhibitors may show benefit in the management of ACD. Rats with oxazolone-induced ACD were found to have less swelling and epidermal thickening in the area of induced dermatitis after treatment with oral tofacitinib, comparable to the effects of cyclosporine. Tofacitinib was presumed to exert its effects through cytokine suppression, particularly that of IFN-γ, IL-22, and tumor necrosis factor α.41 In a separate study on mice with toluene-2,4-diisocyanate–induced ACD, both tofacitinib and another JAK inhibitor, oclacitinib, demonstrated inhibition of cytokine production, migration, and maturation of bone marrow–derived dendritic cells. Both topical and oral formulations of these 2 JAK inhibitors also were found to decrease scratching behavior; only the topicals improved ear thickness (used as a marker of skin inflammation), suggesting potential benefits to local application.42 In a murine model, oral delgocitinib also attenuated contact hypersensitivity via inhibition of antigen-specific T-cell proliferation and cytokine production.37 Finally, in a randomized clinical trial conducted on dogs with allergic dermatitis (of which 10% were presumed to be from contact allergy), oral oclacitinib significantly reduced pruritus and clinical severity scores vs placebo (P<.0001).43
There also are early clinical studies and case reports highlighting the effective use of JAK inhibitors in the management of ACD in humans. A 37-year-old man with occupational airborne ACD to Compositae saw full clearance of his dermatitis with daily oral abrocitinib after topical corticosteroids and dupilumab failed.44 Another patient, a 57-year-old woman, had near-complete resolution of chronic Parthenium-induced airborne ACD after starting twice-daily oral tofacitinib. Allergen avoidance, as well as multiple medications, including topical and oral corticosteroids, topical calcineurin inhibitors, and azathioprine, previously failed in this patient.45 Finally, a phase 2 study on patients with irritant and nonirritant chronic hand eczema found that significantly more patients achieved treatment success (as measured by the physician global assessment) with topical delgocitinib vs vehicle (P=.009).46 Chronic hand eczema may be due to a variety of causes, including AD, irritant contact dermatitis, and ACD. Thus, these studies begin to highlight the potential role for JAK inhibitors in the management of refractory ACD.
Side Effects of JAK Inhibitors
The safety profile of JAK inhibitors must be taken into consideration. In general, topical JAK inhibitors are safe and well tolerated, with the majority of adverse events (AEs) seen in clinical trials considered mild or unrelated to the medication.30,32 Nasopharyngitis, local skin infection, and acne were reported; a systematic review found no increased risk of AEs with topical JAK inhibitors compared with placebo.30,32,47 Application-site reactions, a common concern among the existing topical calcineurin and phosphodiesterase 4 inhibitors, were rare (approximately 2% of patients).47 The most frequent AEs seen in clinical trials of oral JAK inhibitors included acne, nasopharyngitis/upper respiratory tract infections, nausea, and headache.33-35 Herpes simplex virus infection and worsening of AD also were seen. Although elevations in creatine phosphokinase levels were reported, patients often were asymptomatic and elevations were related to exercise or resolved without treatment interruption.33-35
As a class, JAK inhibitors carry a boxed warning for serious infections, malignancy, major adverse cardiovascular events, thrombosis, and mortality. The FDA placed this label on JAK inhibitors because of the results of a randomized controlled trial of oral tofacitinib vs tumor necrosis factor α inhibitors in RA.48,49 Notably, participants in the trial had to be 50 years or older and have at least 1 additional cardiovascular risk factor. Postmarket safety data are still being collected for patients with AD and other dermatologic conditions, but the findings of safety analyses have been reassuring to date.50,51 Regular follow-up and routine laboratory monitoring are recommended for any patient started on an oral JAK inhibitor, which often includes monitoring of the complete blood cell count, comprehensive metabolic panel, and lipids, as well as baseline screening for tuberculosis and hepatitis.52,53 For topical JAK inhibitors, no specific laboratory monitoring is recommended.
Finally, it must be considered that the challenges of off-label prescribing combined with high costs may limit access to JAK inhibitors for use in ACD.
Final Interpretation
Early investigations, including studies on animals and humans, suggest that JAK inhibitors are a promising option in the management of treatment-refractory ACD. Patients and providers should be aware of both the benefits and known side effects of JAK inhibitors prior to treatment initiation.
- Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228:273-287.
- Bousoik E, Montazeri Aliabadi H. “Do we know Jack” about JAK? a closer look at JAK/STAT signaling pathway. Front Oncol. 2018;8:287.
- Jatiani SS, Baker SJ, Silverman LR, et al. Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer. 2010;1:979-993.
- Seif F, Khoshmirsafa M, Aazami H, et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017;15:23.
- Traidl S, Freimooser S, Werfel T. Janus kinase inhibitors for the therapy of atopic dermatitis. Allergol Select. 2021;5:293-304.
- Opzelura (ruxolitinib) cream. Prescribing information. Incyte Corporation; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215309s001lbl.pdf
- Cibinqo (abrocitinib) tablets. Prescribing information. Pfizer Labs; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213871s000lbl.pdf
- Cibinqo. Product information. European Medicines Agency. Published December 17, 2021. Updated November 10, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/cibinqo
- New drugs approved in FY 2021. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000246734.pdf
- Olumiant (baricitinib) tablets. Prescribing information. Eli Lilly and Company; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s007lbl.pdf
- Olumiant. Product information. European Medicines Agency. Published March 16, 2017. Updated June 29, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant
- Review report: Olumiant. Pharmaceuticals and Medical Devices Agency. April 21, 2021. Accessed January 20, 2023. https://www.pmda.go.jp/files/000243207.pdf
- Sotyktu (deucravacitinib) tablets. Prescribing information. Bristol-Myers Squibb Company; 2022. Accessed January 20, 2023.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214958s000lbl.pdf
- Inrebic (fedratinib) capsules. Prescribing information. Celgene Corporation; 2019. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf
- Inrebic. Product information. European Medicines Agency. Published March 3, 2021. Updated December 8, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/inrebic
- Jyseleca. Product information. European Medicines Agency. Published September 28, 2020. Updated November 9, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/documents/product-information/jyseleca-epar-product-information_en.pdf
- Review report: Jyseleca. Pharmaceuticals and Medical Devices Agency. September 8, 2020. Accessed January 20, 2023. https://www.pmda.go.jp/files/000247830.pdf
- Vonjo (pacritinib) capsules. Prescribing information. CTI BioPharma Corp; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208712s000lbl.pdf
- Review report: Smyraf. Pharmaceuticals and Medical Devices Agency. February 28, 2019. Accessed January 20, 2023. https://www.pmda.go.jp/files/000233074.pdf
- Jakafi (ruxolitinib) tablets. Prescribing information. Incyte Corporation; 2021. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202192s023lbl.pdf
- Jakavi. Product information. European Medicines Agency. Published October 4, 2012. Updated May 18, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/jakavi
- New drugs approved in FY 2014. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000229076.pdf
- Xeljanz (tofacitinib). Prescribing information. Pfizer Labs; 2021. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/203214s028,208246s013,213082s003lbl.pdf
- Xeljanz. Product information. European Medicines Agency. Accessed January 20, 2023. https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf
- Review report: Xeljanz. Pharmaceuticals and Medical Devices Agency. January 20, 2023. https://www.pmda.go.jp/files/000237584.pdf
- Rinvoq (upadacitinib) extended-release tablets. Prescribing information. AbbVie Inc; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211675s003lbl.pdf
- Rinvoq. Product information. European Medicines Agency. Published December 18, 2019. Updated December 7, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq
- New drugs approved in FY 2019. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000235289.pdfs
- New drugs approved in May 2022. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000248626.pdf
- Nakagawa H, Nemoto O, Igarashi A, et al. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82:823-831. Erratum appears in J Am Acad Dermatol. 2021;85:1069.
- Sideris N, Paschou E, Bakirtzi K, et al. New and upcoming topical treatments for atopic dermatitis: a review of the literature. J Clin Med. 2022;11:4974.
- Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85:863-872.
- Radi G, Simonetti O, Rizzetto G, et al. Baricitinib: the first Jak inhibitor approved in Europe for the treatment of moderate to severe atopic dermatitis in adult patients. Healthcare (Basel). 2021;9:1575.
- Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021;397:2151-2168. Erratum appears in Lancet. 2021;397:2150.
- Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384:1101-1112.
- Johnson H, Novack DE, Adler BL, et al. Can atopic dermatitis and allergic contact dermatitis coexist? Cutis. 2022;110:139-142.
- Amano W, Nakajima S, Yamamoto Y, et al. JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation. J Dermatol Sci. 2016;84:258-265.
- O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-328.
- Bechara R, Antonios D, Azouri H, et al. Nickel sulfate promotes IL-17A producing CD4+ T cells by an IL-23-dependent mechanism regulated by TLR4 and JAK-STAT pathways. J Invest Dermatol. 2017;137:2140-2148.
- Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171:217-228.e13.
- Fujii Y, Sengoku T. Effects of the Janus kinase inhibitor CP-690550 (tofacitinib) in a rat model of oxazolone-induced chronic dermatitis. Pharmacology. 2013;91:207-213.
- Fukuyama T, Ehling S, Cook E, et al. Topically administered Janus-kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis. J Pharmacol Exp Ther. 2015;354:394-405.
- Cosgrove SB, Wren JA, Cleaver DM, et al. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol. 2013;24:479, E114.
- Baltazar D, Shinamoto SR, Hamann CP, et al. Occupational airborne allergic contact dermatitis to invasive Compositae species treated with abrocitinib: a case report. Contact Dermatitis. 2022;87:542-544.
- Muddebihal A, Sardana K, Sinha S, et al. Tofacitinib in refractory Parthenium-induced airborne allergic contact dermatitis [published online October 12, 2022]. Contact Dermatitis. doi:10.1111/cod.14234
- Worm M, Bauer A, Elsner P, et al. Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study. Br J Dermatol. 2020;182:1103-1110.
- Chen J, Cheng J, Yang H, et al. The efficacy and safety of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and meta-analysis. J Am Acad Dermatol. 2022;87:495-496.
- Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326.
- US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Updated December 7, 2021. Accessed January 20, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
- Chen TL, Lee LL, Huang HK, et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: a systematic review and meta-analysis. JAMA Dermatol. 2022;158:1254-1261.
- King B, Maari C, Lain E, et al. Extended safety analysis of baricitinib 2 mg in adult patients with atopic dermatitis: an integrated analysis from eight randomized clinical trials. Am J Clin Dermatol. 2021;22:395-405.
- Nash P, Kerschbaumer A, Dörner T, et al. Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis. 2021;80:71-87.
- Narla S, Silverberg JI. The suitability of treating atopic dermatitis with Janus kinase inhibitors. Exp Rev Clin Immunol. 2022;18:439-459.
- Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228:273-287.
- Bousoik E, Montazeri Aliabadi H. “Do we know Jack” about JAK? a closer look at JAK/STAT signaling pathway. Front Oncol. 2018;8:287.
- Jatiani SS, Baker SJ, Silverman LR, et al. Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer. 2010;1:979-993.
- Seif F, Khoshmirsafa M, Aazami H, et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017;15:23.
- Traidl S, Freimooser S, Werfel T. Janus kinase inhibitors for the therapy of atopic dermatitis. Allergol Select. 2021;5:293-304.
- Opzelura (ruxolitinib) cream. Prescribing information. Incyte Corporation; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215309s001lbl.pdf
- Cibinqo (abrocitinib) tablets. Prescribing information. Pfizer Labs; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213871s000lbl.pdf
- Cibinqo. Product information. European Medicines Agency. Published December 17, 2021. Updated November 10, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/cibinqo
- New drugs approved in FY 2021. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000246734.pdf
- Olumiant (baricitinib) tablets. Prescribing information. Eli Lilly and Company; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s007lbl.pdf
- Olumiant. Product information. European Medicines Agency. Published March 16, 2017. Updated June 29, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant
- Review report: Olumiant. Pharmaceuticals and Medical Devices Agency. April 21, 2021. Accessed January 20, 2023. https://www.pmda.go.jp/files/000243207.pdf
- Sotyktu (deucravacitinib) tablets. Prescribing information. Bristol-Myers Squibb Company; 2022. Accessed January 20, 2023.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214958s000lbl.pdf
- Inrebic (fedratinib) capsules. Prescribing information. Celgene Corporation; 2019. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212327s000lbl.pdf
- Inrebic. Product information. European Medicines Agency. Published March 3, 2021. Updated December 8, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/inrebic
- Jyseleca. Product information. European Medicines Agency. Published September 28, 2020. Updated November 9, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/documents/product-information/jyseleca-epar-product-information_en.pdf
- Review report: Jyseleca. Pharmaceuticals and Medical Devices Agency. September 8, 2020. Accessed January 20, 2023. https://www.pmda.go.jp/files/000247830.pdf
- Vonjo (pacritinib) capsules. Prescribing information. CTI BioPharma Corp; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208712s000lbl.pdf
- Review report: Smyraf. Pharmaceuticals and Medical Devices Agency. February 28, 2019. Accessed January 20, 2023. https://www.pmda.go.jp/files/000233074.pdf
- Jakafi (ruxolitinib) tablets. Prescribing information. Incyte Corporation; 2021. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202192s023lbl.pdf
- Jakavi. Product information. European Medicines Agency. Published October 4, 2012. Updated May 18, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/jakavi
- New drugs approved in FY 2014. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000229076.pdf
- Xeljanz (tofacitinib). Prescribing information. Pfizer Labs; 2021. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/203214s028,208246s013,213082s003lbl.pdf
- Xeljanz. Product information. European Medicines Agency. Accessed January 20, 2023. https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf
- Review report: Xeljanz. Pharmaceuticals and Medical Devices Agency. January 20, 2023. https://www.pmda.go.jp/files/000237584.pdf
- Rinvoq (upadacitinib) extended-release tablets. Prescribing information. AbbVie Inc; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211675s003lbl.pdf
- Rinvoq. Product information. European Medicines Agency. Published December 18, 2019. Updated December 7, 2022. Accessed January 20, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq
- New drugs approved in FY 2019. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000235289.pdfs
- New drugs approved in May 2022. Pharmaceuticals and Medical Devices Agency. Accessed January 20, 2023. https://www.pmda.go.jp/files/000248626.pdf
- Nakagawa H, Nemoto O, Igarashi A, et al. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82:823-831. Erratum appears in J Am Acad Dermatol. 2021;85:1069.
- Sideris N, Paschou E, Bakirtzi K, et al. New and upcoming topical treatments for atopic dermatitis: a review of the literature. J Clin Med. 2022;11:4974.
- Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85:863-872.
- Radi G, Simonetti O, Rizzetto G, et al. Baricitinib: the first Jak inhibitor approved in Europe for the treatment of moderate to severe atopic dermatitis in adult patients. Healthcare (Basel). 2021;9:1575.
- Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021;397:2151-2168. Erratum appears in Lancet. 2021;397:2150.
- Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384:1101-1112.
- Johnson H, Novack DE, Adler BL, et al. Can atopic dermatitis and allergic contact dermatitis coexist? Cutis. 2022;110:139-142.
- Amano W, Nakajima S, Yamamoto Y, et al. JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation. J Dermatol Sci. 2016;84:258-265.
- O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-328.
- Bechara R, Antonios D, Azouri H, et al. Nickel sulfate promotes IL-17A producing CD4+ T cells by an IL-23-dependent mechanism regulated by TLR4 and JAK-STAT pathways. J Invest Dermatol. 2017;137:2140-2148.
- Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171:217-228.e13.
- Fujii Y, Sengoku T. Effects of the Janus kinase inhibitor CP-690550 (tofacitinib) in a rat model of oxazolone-induced chronic dermatitis. Pharmacology. 2013;91:207-213.
- Fukuyama T, Ehling S, Cook E, et al. Topically administered Janus-kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis. J Pharmacol Exp Ther. 2015;354:394-405.
- Cosgrove SB, Wren JA, Cleaver DM, et al. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol. 2013;24:479, E114.
- Baltazar D, Shinamoto SR, Hamann CP, et al. Occupational airborne allergic contact dermatitis to invasive Compositae species treated with abrocitinib: a case report. Contact Dermatitis. 2022;87:542-544.
- Muddebihal A, Sardana K, Sinha S, et al. Tofacitinib in refractory Parthenium-induced airborne allergic contact dermatitis [published online October 12, 2022]. Contact Dermatitis. doi:10.1111/cod.14234
- Worm M, Bauer A, Elsner P, et al. Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study. Br J Dermatol. 2020;182:1103-1110.
- Chen J, Cheng J, Yang H, et al. The efficacy and safety of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and meta-analysis. J Am Acad Dermatol. 2022;87:495-496.
- Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326.
- US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Updated December 7, 2021. Accessed January 20, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
- Chen TL, Lee LL, Huang HK, et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: a systematic review and meta-analysis. JAMA Dermatol. 2022;158:1254-1261.
- King B, Maari C, Lain E, et al. Extended safety analysis of baricitinib 2 mg in adult patients with atopic dermatitis: an integrated analysis from eight randomized clinical trials. Am J Clin Dermatol. 2021;22:395-405.
- Nash P, Kerschbaumer A, Dörner T, et al. Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis. 2021;80:71-87.
- Narla S, Silverberg JI. The suitability of treating atopic dermatitis with Janus kinase inhibitors. Exp Rev Clin Immunol. 2022;18:439-459.
PRACTICE POINTS
- Janus kinase (JAK) inhibitors are a novel class of small molecule inhibitors that modulate the JAK/signal transducer and activator of transcription signaling pathway.
- Select JAK inhibitors have been approved by the US Food and Drug Administration for the management of atopic dermatitis. Their use in allergic contact dermatitis is under active investigation.
- Regular follow-up and laboratory monitoring for patients on oral JAK inhibitors is recommended, given the potential for treatment-related adverse effects.