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Should Cancer Trial Eligibility Become More Inclusive?
The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.
“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”
Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.
In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.
In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.
Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing.
The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers.
Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.
A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.
The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).
“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.
The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.
So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.
Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.
Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”
However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.
“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”
Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
A version of this article appeared on Medscape.com.
The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.
“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”
Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.
In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.
In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.
Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing.
The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers.
Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.
A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.
The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).
“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.
The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.
So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.
Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.
Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”
However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.
“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”
Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
A version of this article appeared on Medscape.com.
The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.
“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”
Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.
In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.
In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.
Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing.
The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers.
Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.
A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.
The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).
“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.
The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.
So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.
Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.
Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”
However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.
“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”
Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
A version of this article appeared on Medscape.com.
CAR T-Cell Treatment Data Expands in Refractory Rheumatic Diseases, Demonstrating Consistent Efficacy
VIENNA — From a dozen or so studies and sessions devoted to the role of chimeric antigen receptor (CAR) T cells in rheumatic diseases at the annual European Congress of Rheumatology, the message was uniformly positive, supporting growing evidence that drugs in this class are heading toward a paradigm shift in refractory rheumatic diseases.
Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides “the first long-term evidence of safety and efficacy in multiple rheumatic diseases,” according to Georg Schett, MD, PhD, director of rheumatology and immunology, University of Erlangen-Nürnberg, Erlangen, Germany.
The report of high rates of activity and low relative risk of serious adverse events from the same series was published earlier this year in The New England Journal of Medicine when the median follow-up was 15 months. Almost all of the patients have now completed at least 1 year of follow-up and about a third have completed more than 2 years.
SLE Is Frequently Targeted in CAR T-Cell Studies
The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). After the autologous T cells were harvested, they were expanded and transfected with the CD19 CAR. The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight.
The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed.
For the three patients with IIM, all reached the American College of Rheumatology–EULAR criteria for a major response. All creatine kinase levels had normalized by 3 months. In this group, there was one relapse, which occurred after 18 months of follow-up.
All four patients with SSc achieved a major response on the European Scleroderma Trials and Research (EUSTAR) group activity index. The median reduction from baseline in the EUSTAR score was 4.2 points, and this has been maintained in follow-up to date.
Remissions Have Persisted Off All Therapies
These remissions were achieved and maintained after a single dose of CAR T-cell therapy despite discontinuation of all immunosuppressive therapies. With the exception of the single relapse, all remissions have persisted through follow-up to date.
These responses were achieved with manageable side effects, according to Dr. Schett. The most serious adverse event was a grade 4 neutropenia that developed 4 months after receiving CAR T cells. It resolved with granulocyte colony-stimulating factor treatment. Cytokine release syndrome (CRS) has occurred in 10 patients, but it was grade 1 in eight patients and grade 2 in the others. There has been no neurotoxicity.
Almost all patients have experienced an infection during follow-up, but there has been no discernible pattern in relationship to the timing or types of infections. The most common have involved the upper respiratory tract and have been of mild severity, with cases disseminated similarly over early vs late follow-up. There was one case of pneumonia involving antibiotic treatment and a hospital stay, but it resolved.
Dr. Schett acknowledged that safety is a bigger concern in autoimmune diseases, which are often serious but rarely fatal, than in the hematologic malignancies for which CAR T cells were initially tested, but the low rates of serious adverse events in his and other early studies have supported the premise that the risks are not the same.
Asked specifically if CAR T cells can be considered a game changer in autoimmune rheumatic diseases, Dr. Schett was cautious. One reason is the CAR T cells are a complex therapy relative to biologic disease-modifying antirheumatic drugs. He thinks, therefore, that much more data are needed to confirm safety and efficacy. In addition, they are expensive, so it is not yet clear how they will be integrated with other options.
Yet, he thinks the evidence so far suggests a profound effect on the fundamental drivers of autoimmune disease. Their specific mechanism of benefit is still being evaluated, but he considers the clinical responses consistent with a “reset” hypothesis.
After a response, “we are seeing drug-free remissions in some patients as long as they have been followed,” Dr. Schett said. Based on the fact that disease control is being observed off all other therapies, “this only makes sense to me if there is some sort of immunologic reset.”
CAR T-Cell Studies in Autoimmune Diseases Are Proliferating
At last count, there were about 40 studies being performed with CAR T cells in various autoimmune diseases, most of which were rheumatologic disorders, according to Dr. Schett. He noted that funding is coming from multinational drug companies, small biotech startups, and investigator-initiated studies at academic centers.
At EULAR, beyond case studies and anecdotal reports, all of the clinical studies were still at the level of phase 1 or 1/2. Consistent with the data presented by Dr. Schett, the drugs have been nearly uniformly effective, with major responses persisting in patients off other therapies. Adverse events have been manageable.
Examples include a phase 1/2 multinational study with the investigational CAR T-cell therapy YTB323 (Novartis), which demonstrated acceptable safety and a strong signal of benefit in six patients with SLE. In this report, CRS was also common, but no case of CRS was more severe than grade 2. There was no neurotoxicity. Infections did occur but were of relatively mild grades and resolved with treatment.
For efficacy in the ongoing follow-up, SLE symptoms as measured with the SLE Disease Activity Index began to abate at about 14 days after the single-infusion treatment. Improvement on the Physician Global Assessment was also observed between 14 and 28 days. C3 and C4 complement levels started to rise at about 28 days. While the responses have correlated with the observed changes in biomarkers of immune function, they have endured through a median follow-up that now exceeds 6 months.
Complete B-Cell Depletion Is Followed by Full Recovery
“Pharmacokinetic and pharmacodynamic studies revealed peak expansion of CAR T cells approximately 13-21 days post infusion, which was accompanied by deep B-cell depletion followed by subsequent B-cell recovery,” reported Josefina Cortés-Hernández, MD, PhD, a senior lecturer at Vall d’Hebron Research Institute, Barcelona, Spain.
Dr. Schett had reported the same pattern of expansion followed by a rapid elimination of detectable CAR T cells despite the sustained clinical benefit.
Dr. Cortés-Hernández said that the signal of efficacy in the context of acceptable safety supports an expansion of clinical studies with this CAR T-cell product in SLE and perhaps other autoimmune disorders.
In another early-stage study, patients with SLE who had failed multiple prior lines of therapy have been enrolled in an ongoing study with a compound CAR (cCAR) T cell. This experimental proprietary product (iCAR Bio Therapeutics, Zhongshan, China) targets both the B-cell maturation antigen and CD19, according to Greg Deener, the chief executive officer of iCell Gene Therapeutics, New York City.
cCAR T-Cell Construct Targets Immune Reset
With this construct, the goal is to deplete long-lived plasma cells as well as B cells in order to achieve a more complete humoral reset. While preliminary data from the phase 1 trial were published earlier this year in Annals of the Rheumatic Diseases, Mr. Deener focused his presentation at EULAR 2024 on 12 patients with SLE and lupus nephritis, a severe form of SLE that threatens glomerular structures and can lead to end-stage liver disease.
B cells in the peripheral blood could not be detected within 10 days of the cCAR infusion, and the immunoglobulins IgM and IgA were undetectable by day 42.
However, after B-cell recovery by day 150, “flow cytometry and B-cell receptor sequencing confirmed full humoral reset was achieved,” Mr. Deener said.
The remission has been durable in 11 of the 12 patients after a mean follow-up of 458 days, Mr. Deener reported. He noted that an improvement in renal function has been observed in the majority of patients.
Like others, he reported that treatment has been relatively well tolerated. In this series of patients, there have been no cases of CRS more severe than grade 1.
Overall, the cCAR data in lupus nephritis support the hypothesis that CAR T cells are reprogramming the immune system, according to Mr. Deener.
Combined with a reasonable safety profile, the consistency of benefit from CAR T cells in autoimmune rheumatic diseases is good news, but all of the investigators who spoke at EULAR agreed that there are still many unanswered questions. Not least, it is unclear whether patients can be effectively and safely retreated when and if relapses occur. Even though Dr. Schett did report a response with retreatment following a relapse, he said that there is no conclusion to draw from a single patient.
Yet, the high rates of remissions in patients with disease refractory to other therapeutic options is highly encouraging, particularly with the manageable side effects now reported by multiple investigators using different CAR T-cell products.
“Roughly 100 patients with rheumatic diseases have been treated with CAR T-cells, and we have not seen a high-grade CRS or neurotoxicity,” he said.
Long-term efficacy is less clear. With the first clinical studies in autoimmune diseases initiated in 2021, few patients have been followed for more than 2 years. Even with the high rates of response that will certainly fuel efforts to rapidly bring these treatments forward, long-term data are now the missing piece.
Other Case Series Presented at EULAR
Several other abstracts reported on patients with SSc who were treated with CD19-targeting CAR T cells:
Three patients for whom autologous hematopoietic stem cell transplantation was contraindicated or unsuccessful were successfully and safely treated.
Six patients with diffuse and progressive disease achieved stable disease activity without additional immunosuppression for up to 1 year after treatment.
Dr. Schett reported no potential conflicts of interest, and the study he presented was not funded by industry. Dr. Cortés-Hernández reported a financial relationship with Novartis, which funded the study of the CAR T-cell therapy YTB323, as well as with GlaxoSmithKline, which was not involved in the study she presented. Mr. Deener is an employee of iCell Gene Therapeutics, which provided funding for the trial he presented.
August 7, 2024 — Editor's note: This article was updated with additional disclosure information for Dr. Josefina Cortés-Hernández.
A version of this article appeared on Medscape.com.
VIENNA — From a dozen or so studies and sessions devoted to the role of chimeric antigen receptor (CAR) T cells in rheumatic diseases at the annual European Congress of Rheumatology, the message was uniformly positive, supporting growing evidence that drugs in this class are heading toward a paradigm shift in refractory rheumatic diseases.
Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides “the first long-term evidence of safety and efficacy in multiple rheumatic diseases,” according to Georg Schett, MD, PhD, director of rheumatology and immunology, University of Erlangen-Nürnberg, Erlangen, Germany.
The report of high rates of activity and low relative risk of serious adverse events from the same series was published earlier this year in The New England Journal of Medicine when the median follow-up was 15 months. Almost all of the patients have now completed at least 1 year of follow-up and about a third have completed more than 2 years.
SLE Is Frequently Targeted in CAR T-Cell Studies
The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). After the autologous T cells were harvested, they were expanded and transfected with the CD19 CAR. The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight.
The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed.
For the three patients with IIM, all reached the American College of Rheumatology–EULAR criteria for a major response. All creatine kinase levels had normalized by 3 months. In this group, there was one relapse, which occurred after 18 months of follow-up.
All four patients with SSc achieved a major response on the European Scleroderma Trials and Research (EUSTAR) group activity index. The median reduction from baseline in the EUSTAR score was 4.2 points, and this has been maintained in follow-up to date.
Remissions Have Persisted Off All Therapies
These remissions were achieved and maintained after a single dose of CAR T-cell therapy despite discontinuation of all immunosuppressive therapies. With the exception of the single relapse, all remissions have persisted through follow-up to date.
These responses were achieved with manageable side effects, according to Dr. Schett. The most serious adverse event was a grade 4 neutropenia that developed 4 months after receiving CAR T cells. It resolved with granulocyte colony-stimulating factor treatment. Cytokine release syndrome (CRS) has occurred in 10 patients, but it was grade 1 in eight patients and grade 2 in the others. There has been no neurotoxicity.
Almost all patients have experienced an infection during follow-up, but there has been no discernible pattern in relationship to the timing or types of infections. The most common have involved the upper respiratory tract and have been of mild severity, with cases disseminated similarly over early vs late follow-up. There was one case of pneumonia involving antibiotic treatment and a hospital stay, but it resolved.
Dr. Schett acknowledged that safety is a bigger concern in autoimmune diseases, which are often serious but rarely fatal, than in the hematologic malignancies for which CAR T cells were initially tested, but the low rates of serious adverse events in his and other early studies have supported the premise that the risks are not the same.
Asked specifically if CAR T cells can be considered a game changer in autoimmune rheumatic diseases, Dr. Schett was cautious. One reason is the CAR T cells are a complex therapy relative to biologic disease-modifying antirheumatic drugs. He thinks, therefore, that much more data are needed to confirm safety and efficacy. In addition, they are expensive, so it is not yet clear how they will be integrated with other options.
Yet, he thinks the evidence so far suggests a profound effect on the fundamental drivers of autoimmune disease. Their specific mechanism of benefit is still being evaluated, but he considers the clinical responses consistent with a “reset” hypothesis.
After a response, “we are seeing drug-free remissions in some patients as long as they have been followed,” Dr. Schett said. Based on the fact that disease control is being observed off all other therapies, “this only makes sense to me if there is some sort of immunologic reset.”
CAR T-Cell Studies in Autoimmune Diseases Are Proliferating
At last count, there were about 40 studies being performed with CAR T cells in various autoimmune diseases, most of which were rheumatologic disorders, according to Dr. Schett. He noted that funding is coming from multinational drug companies, small biotech startups, and investigator-initiated studies at academic centers.
At EULAR, beyond case studies and anecdotal reports, all of the clinical studies were still at the level of phase 1 or 1/2. Consistent with the data presented by Dr. Schett, the drugs have been nearly uniformly effective, with major responses persisting in patients off other therapies. Adverse events have been manageable.
Examples include a phase 1/2 multinational study with the investigational CAR T-cell therapy YTB323 (Novartis), which demonstrated acceptable safety and a strong signal of benefit in six patients with SLE. In this report, CRS was also common, but no case of CRS was more severe than grade 2. There was no neurotoxicity. Infections did occur but were of relatively mild grades and resolved with treatment.
For efficacy in the ongoing follow-up, SLE symptoms as measured with the SLE Disease Activity Index began to abate at about 14 days after the single-infusion treatment. Improvement on the Physician Global Assessment was also observed between 14 and 28 days. C3 and C4 complement levels started to rise at about 28 days. While the responses have correlated with the observed changes in biomarkers of immune function, they have endured through a median follow-up that now exceeds 6 months.
Complete B-Cell Depletion Is Followed by Full Recovery
“Pharmacokinetic and pharmacodynamic studies revealed peak expansion of CAR T cells approximately 13-21 days post infusion, which was accompanied by deep B-cell depletion followed by subsequent B-cell recovery,” reported Josefina Cortés-Hernández, MD, PhD, a senior lecturer at Vall d’Hebron Research Institute, Barcelona, Spain.
Dr. Schett had reported the same pattern of expansion followed by a rapid elimination of detectable CAR T cells despite the sustained clinical benefit.
Dr. Cortés-Hernández said that the signal of efficacy in the context of acceptable safety supports an expansion of clinical studies with this CAR T-cell product in SLE and perhaps other autoimmune disorders.
In another early-stage study, patients with SLE who had failed multiple prior lines of therapy have been enrolled in an ongoing study with a compound CAR (cCAR) T cell. This experimental proprietary product (iCAR Bio Therapeutics, Zhongshan, China) targets both the B-cell maturation antigen and CD19, according to Greg Deener, the chief executive officer of iCell Gene Therapeutics, New York City.
cCAR T-Cell Construct Targets Immune Reset
With this construct, the goal is to deplete long-lived plasma cells as well as B cells in order to achieve a more complete humoral reset. While preliminary data from the phase 1 trial were published earlier this year in Annals of the Rheumatic Diseases, Mr. Deener focused his presentation at EULAR 2024 on 12 patients with SLE and lupus nephritis, a severe form of SLE that threatens glomerular structures and can lead to end-stage liver disease.
B cells in the peripheral blood could not be detected within 10 days of the cCAR infusion, and the immunoglobulins IgM and IgA were undetectable by day 42.
However, after B-cell recovery by day 150, “flow cytometry and B-cell receptor sequencing confirmed full humoral reset was achieved,” Mr. Deener said.
The remission has been durable in 11 of the 12 patients after a mean follow-up of 458 days, Mr. Deener reported. He noted that an improvement in renal function has been observed in the majority of patients.
Like others, he reported that treatment has been relatively well tolerated. In this series of patients, there have been no cases of CRS more severe than grade 1.
Overall, the cCAR data in lupus nephritis support the hypothesis that CAR T cells are reprogramming the immune system, according to Mr. Deener.
Combined with a reasonable safety profile, the consistency of benefit from CAR T cells in autoimmune rheumatic diseases is good news, but all of the investigators who spoke at EULAR agreed that there are still many unanswered questions. Not least, it is unclear whether patients can be effectively and safely retreated when and if relapses occur. Even though Dr. Schett did report a response with retreatment following a relapse, he said that there is no conclusion to draw from a single patient.
Yet, the high rates of remissions in patients with disease refractory to other therapeutic options is highly encouraging, particularly with the manageable side effects now reported by multiple investigators using different CAR T-cell products.
“Roughly 100 patients with rheumatic diseases have been treated with CAR T-cells, and we have not seen a high-grade CRS or neurotoxicity,” he said.
Long-term efficacy is less clear. With the first clinical studies in autoimmune diseases initiated in 2021, few patients have been followed for more than 2 years. Even with the high rates of response that will certainly fuel efforts to rapidly bring these treatments forward, long-term data are now the missing piece.
Other Case Series Presented at EULAR
Several other abstracts reported on patients with SSc who were treated with CD19-targeting CAR T cells:
Three patients for whom autologous hematopoietic stem cell transplantation was contraindicated or unsuccessful were successfully and safely treated.
Six patients with diffuse and progressive disease achieved stable disease activity without additional immunosuppression for up to 1 year after treatment.
Dr. Schett reported no potential conflicts of interest, and the study he presented was not funded by industry. Dr. Cortés-Hernández reported a financial relationship with Novartis, which funded the study of the CAR T-cell therapy YTB323, as well as with GlaxoSmithKline, which was not involved in the study she presented. Mr. Deener is an employee of iCell Gene Therapeutics, which provided funding for the trial he presented.
August 7, 2024 — Editor's note: This article was updated with additional disclosure information for Dr. Josefina Cortés-Hernández.
A version of this article appeared on Medscape.com.
VIENNA — From a dozen or so studies and sessions devoted to the role of chimeric antigen receptor (CAR) T cells in rheumatic diseases at the annual European Congress of Rheumatology, the message was uniformly positive, supporting growing evidence that drugs in this class are heading toward a paradigm shift in refractory rheumatic diseases.
Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides “the first long-term evidence of safety and efficacy in multiple rheumatic diseases,” according to Georg Schett, MD, PhD, director of rheumatology and immunology, University of Erlangen-Nürnberg, Erlangen, Germany.
The report of high rates of activity and low relative risk of serious adverse events from the same series was published earlier this year in The New England Journal of Medicine when the median follow-up was 15 months. Almost all of the patients have now completed at least 1 year of follow-up and about a third have completed more than 2 years.
SLE Is Frequently Targeted in CAR T-Cell Studies
The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). After the autologous T cells were harvested, they were expanded and transfected with the CD19 CAR. The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight.
The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed.
For the three patients with IIM, all reached the American College of Rheumatology–EULAR criteria for a major response. All creatine kinase levels had normalized by 3 months. In this group, there was one relapse, which occurred after 18 months of follow-up.
All four patients with SSc achieved a major response on the European Scleroderma Trials and Research (EUSTAR) group activity index. The median reduction from baseline in the EUSTAR score was 4.2 points, and this has been maintained in follow-up to date.
Remissions Have Persisted Off All Therapies
These remissions were achieved and maintained after a single dose of CAR T-cell therapy despite discontinuation of all immunosuppressive therapies. With the exception of the single relapse, all remissions have persisted through follow-up to date.
These responses were achieved with manageable side effects, according to Dr. Schett. The most serious adverse event was a grade 4 neutropenia that developed 4 months after receiving CAR T cells. It resolved with granulocyte colony-stimulating factor treatment. Cytokine release syndrome (CRS) has occurred in 10 patients, but it was grade 1 in eight patients and grade 2 in the others. There has been no neurotoxicity.
Almost all patients have experienced an infection during follow-up, but there has been no discernible pattern in relationship to the timing or types of infections. The most common have involved the upper respiratory tract and have been of mild severity, with cases disseminated similarly over early vs late follow-up. There was one case of pneumonia involving antibiotic treatment and a hospital stay, but it resolved.
Dr. Schett acknowledged that safety is a bigger concern in autoimmune diseases, which are often serious but rarely fatal, than in the hematologic malignancies for which CAR T cells were initially tested, but the low rates of serious adverse events in his and other early studies have supported the premise that the risks are not the same.
Asked specifically if CAR T cells can be considered a game changer in autoimmune rheumatic diseases, Dr. Schett was cautious. One reason is the CAR T cells are a complex therapy relative to biologic disease-modifying antirheumatic drugs. He thinks, therefore, that much more data are needed to confirm safety and efficacy. In addition, they are expensive, so it is not yet clear how they will be integrated with other options.
Yet, he thinks the evidence so far suggests a profound effect on the fundamental drivers of autoimmune disease. Their specific mechanism of benefit is still being evaluated, but he considers the clinical responses consistent with a “reset” hypothesis.
After a response, “we are seeing drug-free remissions in some patients as long as they have been followed,” Dr. Schett said. Based on the fact that disease control is being observed off all other therapies, “this only makes sense to me if there is some sort of immunologic reset.”
CAR T-Cell Studies in Autoimmune Diseases Are Proliferating
At last count, there were about 40 studies being performed with CAR T cells in various autoimmune diseases, most of which were rheumatologic disorders, according to Dr. Schett. He noted that funding is coming from multinational drug companies, small biotech startups, and investigator-initiated studies at academic centers.
At EULAR, beyond case studies and anecdotal reports, all of the clinical studies were still at the level of phase 1 or 1/2. Consistent with the data presented by Dr. Schett, the drugs have been nearly uniformly effective, with major responses persisting in patients off other therapies. Adverse events have been manageable.
Examples include a phase 1/2 multinational study with the investigational CAR T-cell therapy YTB323 (Novartis), which demonstrated acceptable safety and a strong signal of benefit in six patients with SLE. In this report, CRS was also common, but no case of CRS was more severe than grade 2. There was no neurotoxicity. Infections did occur but were of relatively mild grades and resolved with treatment.
For efficacy in the ongoing follow-up, SLE symptoms as measured with the SLE Disease Activity Index began to abate at about 14 days after the single-infusion treatment. Improvement on the Physician Global Assessment was also observed between 14 and 28 days. C3 and C4 complement levels started to rise at about 28 days. While the responses have correlated with the observed changes in biomarkers of immune function, they have endured through a median follow-up that now exceeds 6 months.
Complete B-Cell Depletion Is Followed by Full Recovery
“Pharmacokinetic and pharmacodynamic studies revealed peak expansion of CAR T cells approximately 13-21 days post infusion, which was accompanied by deep B-cell depletion followed by subsequent B-cell recovery,” reported Josefina Cortés-Hernández, MD, PhD, a senior lecturer at Vall d’Hebron Research Institute, Barcelona, Spain.
Dr. Schett had reported the same pattern of expansion followed by a rapid elimination of detectable CAR T cells despite the sustained clinical benefit.
Dr. Cortés-Hernández said that the signal of efficacy in the context of acceptable safety supports an expansion of clinical studies with this CAR T-cell product in SLE and perhaps other autoimmune disorders.
In another early-stage study, patients with SLE who had failed multiple prior lines of therapy have been enrolled in an ongoing study with a compound CAR (cCAR) T cell. This experimental proprietary product (iCAR Bio Therapeutics, Zhongshan, China) targets both the B-cell maturation antigen and CD19, according to Greg Deener, the chief executive officer of iCell Gene Therapeutics, New York City.
cCAR T-Cell Construct Targets Immune Reset
With this construct, the goal is to deplete long-lived plasma cells as well as B cells in order to achieve a more complete humoral reset. While preliminary data from the phase 1 trial were published earlier this year in Annals of the Rheumatic Diseases, Mr. Deener focused his presentation at EULAR 2024 on 12 patients with SLE and lupus nephritis, a severe form of SLE that threatens glomerular structures and can lead to end-stage liver disease.
B cells in the peripheral blood could not be detected within 10 days of the cCAR infusion, and the immunoglobulins IgM and IgA were undetectable by day 42.
However, after B-cell recovery by day 150, “flow cytometry and B-cell receptor sequencing confirmed full humoral reset was achieved,” Mr. Deener said.
The remission has been durable in 11 of the 12 patients after a mean follow-up of 458 days, Mr. Deener reported. He noted that an improvement in renal function has been observed in the majority of patients.
Like others, he reported that treatment has been relatively well tolerated. In this series of patients, there have been no cases of CRS more severe than grade 1.
Overall, the cCAR data in lupus nephritis support the hypothesis that CAR T cells are reprogramming the immune system, according to Mr. Deener.
Combined with a reasonable safety profile, the consistency of benefit from CAR T cells in autoimmune rheumatic diseases is good news, but all of the investigators who spoke at EULAR agreed that there are still many unanswered questions. Not least, it is unclear whether patients can be effectively and safely retreated when and if relapses occur. Even though Dr. Schett did report a response with retreatment following a relapse, he said that there is no conclusion to draw from a single patient.
Yet, the high rates of remissions in patients with disease refractory to other therapeutic options is highly encouraging, particularly with the manageable side effects now reported by multiple investigators using different CAR T-cell products.
“Roughly 100 patients with rheumatic diseases have been treated with CAR T-cells, and we have not seen a high-grade CRS or neurotoxicity,” he said.
Long-term efficacy is less clear. With the first clinical studies in autoimmune diseases initiated in 2021, few patients have been followed for more than 2 years. Even with the high rates of response that will certainly fuel efforts to rapidly bring these treatments forward, long-term data are now the missing piece.
Other Case Series Presented at EULAR
Several other abstracts reported on patients with SSc who were treated with CD19-targeting CAR T cells:
Three patients for whom autologous hematopoietic stem cell transplantation was contraindicated or unsuccessful were successfully and safely treated.
Six patients with diffuse and progressive disease achieved stable disease activity without additional immunosuppression for up to 1 year after treatment.
Dr. Schett reported no potential conflicts of interest, and the study he presented was not funded by industry. Dr. Cortés-Hernández reported a financial relationship with Novartis, which funded the study of the CAR T-cell therapy YTB323, as well as with GlaxoSmithKline, which was not involved in the study she presented. Mr. Deener is an employee of iCell Gene Therapeutics, which provided funding for the trial he presented.
August 7, 2024 — Editor's note: This article was updated with additional disclosure information for Dr. Josefina Cortés-Hernández.
A version of this article appeared on Medscape.com.
FROM EULAR 2024
How Dermatologists Can Safeguard Against Malpractice Claims
for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.
“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.
Trends in Dermatology Malpractice
This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.
“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.
About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.
“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”
Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.
Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.
The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
Training Is a Must — But Not Standardized
Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.
However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”
Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.
The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.
“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.
Ins and Outs of Informed Consent
When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.
“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”
The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.
“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”
A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”
Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.
He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”
Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.
Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.
That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.
Dr. Stratman and Dr. Avram had no relevant disclosures.
A version of this article appeared on Medscape.com.
for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.
“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.
Trends in Dermatology Malpractice
This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.
“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.
About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.
“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”
Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.
Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.
The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
Training Is a Must — But Not Standardized
Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.
However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”
Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.
The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.
“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.
Ins and Outs of Informed Consent
When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.
“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”
The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.
“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”
A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”
Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.
He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”
Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.
Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.
That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.
Dr. Stratman and Dr. Avram had no relevant disclosures.
A version of this article appeared on Medscape.com.
for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.
“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.
Trends in Dermatology Malpractice
This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.
“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.
About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.
“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”
Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.
Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.
The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
Training Is a Must — But Not Standardized
Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.
However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”
Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.
The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.
“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.
Ins and Outs of Informed Consent
When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.
“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”
The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.
“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”
A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”
Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.
He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”
Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.
Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.
That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.
Dr. Stratman and Dr. Avram had no relevant disclosures.
A version of this article appeared on Medscape.com.
Cosmetic Botulinum Toxin A Doses May Differ in Sunny Climates
findings from a comparative cohort study suggested.
“Botulinum toxin A to the glabella is a popular cosmetic intervention,” researchers led by Kim L. Borsky, MD, MBBS, of the Department of Plastic and Reconstructive Surgery at Stoke Mandeville Hospital, Aylesbury, England, and colleagues wrote in their study, which was published in Plastic and Reconstructive Surgery. “Functional musculature differences may arise from chronic behavioral adjustment to high sun exposure levels, requiring greater doses. This could affect clinical practice globally.”
To investigate the effect of climate on real-world doses of the product, the researchers enrolled 523 women aged 35-60 years who received glabellar botulinum toxin treatment at two centers between 2012 and 2019: one in the United Kingdom and one in Malta. They evaluated data on 292 patients treated during the summer months at the Malta center (classified as the high sun-exposure group), and 231 patients treated during the winter months at the UK center (classified as the low sun-exposure group). The primary outcomes of interest were the required top-up doses and the total dose to achieve full paralysis. Smokers were excluded from the analysis, as were those who did not seek maximal paralysis, those documented as not compliant with posttreatment advice, and those with colds or fevers. They used univariable and multivariable analyses to compare the high vs low sun-exposure groups.
The researchers found that 68.5% of women in the high-sun group required a top-up dose to achieve full paralysis, compared with 61.5% in the low-sun group, a difference that did not reach statistical significance (P = .1032). All patients achieved full paralysis with the treatment protocol used. However, in the high-sun group, the mean top-up dose was significantly higher than that in the low-sun group (a mean of 9.30 vs 7.06 units, respectively; P = .0009), as was the mean total dose (a mean of 29.23 vs 27.25 units; P = .0031).
“Patients subject to less sun exposure require a lower dose than patients with high sun exposure, and this was present and persisted when controlling for potential confounders,” the researchers wrote. “Although robustly demonstrated, the difference in doses seen here was small, and so may not directly impact at a health economic level, as the difference would not necessarily change the number of vials used. However, it may be of relevance to training and protocolization of treatments. Rigid protocols about doses and distributions may lead to undertreatment if applied in sunnier climates.”
They acknowledged certain limitations of their study, including its unblinded design and the fact that they did not evaluate or control for ethnicity. They also characterized the population of Malta as “very homogeneous, mainly made up of Maltese with less than 5% foreigners,” while the demographics of the United Kingdom and especially London, where the injections were performed, “are much more diverse.”
Asked to comment on the results, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, DC, said that the study highlights the importance of tailoring neuromodulator treatment to the individual patient based not just on gender but also on lifestyle and climate. “The conclusion [of the study] is logical, but it’s encouraging that the data supports this,” Dr. Sodha told this news organization. “The potential confounders, such as injection technique (5 point vs 3 point), nonblinding of the evaluator, history of prior treatments, and variation in treatment effect by different botulinum toxin products may be important as well in how we consider this data in practice.”
This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Neither the researchers nor Dr. Sodha reported having financial disclosures.
A version of this article appeared on Medscape.com.
findings from a comparative cohort study suggested.
“Botulinum toxin A to the glabella is a popular cosmetic intervention,” researchers led by Kim L. Borsky, MD, MBBS, of the Department of Plastic and Reconstructive Surgery at Stoke Mandeville Hospital, Aylesbury, England, and colleagues wrote in their study, which was published in Plastic and Reconstructive Surgery. “Functional musculature differences may arise from chronic behavioral adjustment to high sun exposure levels, requiring greater doses. This could affect clinical practice globally.”
To investigate the effect of climate on real-world doses of the product, the researchers enrolled 523 women aged 35-60 years who received glabellar botulinum toxin treatment at two centers between 2012 and 2019: one in the United Kingdom and one in Malta. They evaluated data on 292 patients treated during the summer months at the Malta center (classified as the high sun-exposure group), and 231 patients treated during the winter months at the UK center (classified as the low sun-exposure group). The primary outcomes of interest were the required top-up doses and the total dose to achieve full paralysis. Smokers were excluded from the analysis, as were those who did not seek maximal paralysis, those documented as not compliant with posttreatment advice, and those with colds or fevers. They used univariable and multivariable analyses to compare the high vs low sun-exposure groups.
The researchers found that 68.5% of women in the high-sun group required a top-up dose to achieve full paralysis, compared with 61.5% in the low-sun group, a difference that did not reach statistical significance (P = .1032). All patients achieved full paralysis with the treatment protocol used. However, in the high-sun group, the mean top-up dose was significantly higher than that in the low-sun group (a mean of 9.30 vs 7.06 units, respectively; P = .0009), as was the mean total dose (a mean of 29.23 vs 27.25 units; P = .0031).
“Patients subject to less sun exposure require a lower dose than patients with high sun exposure, and this was present and persisted when controlling for potential confounders,” the researchers wrote. “Although robustly demonstrated, the difference in doses seen here was small, and so may not directly impact at a health economic level, as the difference would not necessarily change the number of vials used. However, it may be of relevance to training and protocolization of treatments. Rigid protocols about doses and distributions may lead to undertreatment if applied in sunnier climates.”
They acknowledged certain limitations of their study, including its unblinded design and the fact that they did not evaluate or control for ethnicity. They also characterized the population of Malta as “very homogeneous, mainly made up of Maltese with less than 5% foreigners,” while the demographics of the United Kingdom and especially London, where the injections were performed, “are much more diverse.”
Asked to comment on the results, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, DC, said that the study highlights the importance of tailoring neuromodulator treatment to the individual patient based not just on gender but also on lifestyle and climate. “The conclusion [of the study] is logical, but it’s encouraging that the data supports this,” Dr. Sodha told this news organization. “The potential confounders, such as injection technique (5 point vs 3 point), nonblinding of the evaluator, history of prior treatments, and variation in treatment effect by different botulinum toxin products may be important as well in how we consider this data in practice.”
This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Neither the researchers nor Dr. Sodha reported having financial disclosures.
A version of this article appeared on Medscape.com.
findings from a comparative cohort study suggested.
“Botulinum toxin A to the glabella is a popular cosmetic intervention,” researchers led by Kim L. Borsky, MD, MBBS, of the Department of Plastic and Reconstructive Surgery at Stoke Mandeville Hospital, Aylesbury, England, and colleagues wrote in their study, which was published in Plastic and Reconstructive Surgery. “Functional musculature differences may arise from chronic behavioral adjustment to high sun exposure levels, requiring greater doses. This could affect clinical practice globally.”
To investigate the effect of climate on real-world doses of the product, the researchers enrolled 523 women aged 35-60 years who received glabellar botulinum toxin treatment at two centers between 2012 and 2019: one in the United Kingdom and one in Malta. They evaluated data on 292 patients treated during the summer months at the Malta center (classified as the high sun-exposure group), and 231 patients treated during the winter months at the UK center (classified as the low sun-exposure group). The primary outcomes of interest were the required top-up doses and the total dose to achieve full paralysis. Smokers were excluded from the analysis, as were those who did not seek maximal paralysis, those documented as not compliant with posttreatment advice, and those with colds or fevers. They used univariable and multivariable analyses to compare the high vs low sun-exposure groups.
The researchers found that 68.5% of women in the high-sun group required a top-up dose to achieve full paralysis, compared with 61.5% in the low-sun group, a difference that did not reach statistical significance (P = .1032). All patients achieved full paralysis with the treatment protocol used. However, in the high-sun group, the mean top-up dose was significantly higher than that in the low-sun group (a mean of 9.30 vs 7.06 units, respectively; P = .0009), as was the mean total dose (a mean of 29.23 vs 27.25 units; P = .0031).
“Patients subject to less sun exposure require a lower dose than patients with high sun exposure, and this was present and persisted when controlling for potential confounders,” the researchers wrote. “Although robustly demonstrated, the difference in doses seen here was small, and so may not directly impact at a health economic level, as the difference would not necessarily change the number of vials used. However, it may be of relevance to training and protocolization of treatments. Rigid protocols about doses and distributions may lead to undertreatment if applied in sunnier climates.”
They acknowledged certain limitations of their study, including its unblinded design and the fact that they did not evaluate or control for ethnicity. They also characterized the population of Malta as “very homogeneous, mainly made up of Maltese with less than 5% foreigners,” while the demographics of the United Kingdom and especially London, where the injections were performed, “are much more diverse.”
Asked to comment on the results, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, DC, said that the study highlights the importance of tailoring neuromodulator treatment to the individual patient based not just on gender but also on lifestyle and climate. “The conclusion [of the study] is logical, but it’s encouraging that the data supports this,” Dr. Sodha told this news organization. “The potential confounders, such as injection technique (5 point vs 3 point), nonblinding of the evaluator, history of prior treatments, and variation in treatment effect by different botulinum toxin products may be important as well in how we consider this data in practice.”
This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Neither the researchers nor Dr. Sodha reported having financial disclosures.
A version of this article appeared on Medscape.com.
FROM PLASTIC AND RECONSTRUCTIVE SURGERY
Draining Nodule of the Hand
The Diagnosis: Cutaneous Nocardiosis
The wound culture was positive for Nocardia farcinica. The patient received a 5-day course of intravenous sulfamethoxazole-trimethoprim in the hospital and was transitioned to oral sulfamethoxazoletrimethoprim (800 mg/160 mg taken as 1 tablet twice daily) for 6 months. Complete resolution of the infection was noted at 6-month follow-up (Figure).
Nocardia is a gram-positive, aerobic bacterium that typically is found in soil, water, and decaying organic matter.1 There are more than 50 species; N farcinica, Nocardia nova, and Nocardia asteroides are the leading causes of infection in humans and animals. Nocardia asteroides is the most common cause of infection in humans.1,2 Nocardiosis is an uncommon opportunistic infection that usually targets the skin, lungs, and central nervous system.3 Although it mainly affects individuals who are immunocompromised, up to 30% of infections can be seen in immunocompetent hosts who can contract cutaneous nocardiosis after experiencing traumatic injury to the skin.1
Nocardiosis is difficult to diagnose due to its diverse clinical presentations. For example, cutaneous nocardiosis can manifest similar to mycetoma, sporotrichosis, spider bites, nontuberculous mycobacteria such as Mycobacterium marinum, or methicillin-resistant Staphylococcus aureus infections, thus making cutaneous nocardiosis one of the great imitators.1 A culture is required for definitive diagnosis, as Nocardia grows well on nonselective media such as blood or Löwenstein-Jensen agar. It grows as waxy, pigmented, cerebriform colonies 3 to 5 days following incubation.3 The bacterium can be difficult to culture, and it is important to notify the microbiology laboratory if there is a high index of clinical suspicion for infection.
A history of exposure to gardening or handling animals can increase the risk for an individual contracting Nocardia.3 Although nocardiosis can be found across the world, it is native to tropical and subtropical climates such as those found in India, Africa, Latin America, and Southeast Asia.1 Infections mostly are observed in individuals aged 20 to 40 years and tend to affect men more than women. Lesions typically are seen on the lower extremities, but localized infections also can be found on the torso, neck, and upper extremities.1
Cutaneous nocardiosis is a granulomatous infection encompassing both cutaneous and subcutaneous tissue, which ultimately can lead to injury of bone and viscera.1 Primary cutaneous nocardiosis can manifest as tumors or nodules that have a sporotrichoid pattern, in which they ascend along the lymphatics. Histopathology of infected tissue frequently shows a subcutaneous dermal infiltrate of neutrophils accompanied with abscess formation, and everlasting lesions may show signs of chronic inflammation and nonspecific granulomas.3
Treatment of nocardiosis should be guided by in vitro susceptibility tests. Sulfamethoxazole-trimethoprim 800 mg/160 mg taken as 1 tablet twice daily is the first-line option. The treatment duration is contingent on the extent, severity, and complications of infection but typically is 3 to 6 months.1
- Yu Q, Song J, Liu Y, et al. Progressive primary cutaneous nocardiosis in an immunocompetent patient. Cutis. 2023;111:E22-E25.
- Gaines RJ, Randall CJ, Ruland RT. Lymphocutaneous nocardiosis from commercially treated lumber: a case report. Cutis. 2006;78:249-251.
- Riswold KJ, Tjarks BJ, Kerkvliet AM. Cutaneous nocardiosis in an immunocompromised patient. Cutis. 2019;104:226-229.
The Diagnosis: Cutaneous Nocardiosis
The wound culture was positive for Nocardia farcinica. The patient received a 5-day course of intravenous sulfamethoxazole-trimethoprim in the hospital and was transitioned to oral sulfamethoxazoletrimethoprim (800 mg/160 mg taken as 1 tablet twice daily) for 6 months. Complete resolution of the infection was noted at 6-month follow-up (Figure).
Nocardia is a gram-positive, aerobic bacterium that typically is found in soil, water, and decaying organic matter.1 There are more than 50 species; N farcinica, Nocardia nova, and Nocardia asteroides are the leading causes of infection in humans and animals. Nocardia asteroides is the most common cause of infection in humans.1,2 Nocardiosis is an uncommon opportunistic infection that usually targets the skin, lungs, and central nervous system.3 Although it mainly affects individuals who are immunocompromised, up to 30% of infections can be seen in immunocompetent hosts who can contract cutaneous nocardiosis after experiencing traumatic injury to the skin.1
Nocardiosis is difficult to diagnose due to its diverse clinical presentations. For example, cutaneous nocardiosis can manifest similar to mycetoma, sporotrichosis, spider bites, nontuberculous mycobacteria such as Mycobacterium marinum, or methicillin-resistant Staphylococcus aureus infections, thus making cutaneous nocardiosis one of the great imitators.1 A culture is required for definitive diagnosis, as Nocardia grows well on nonselective media such as blood or Löwenstein-Jensen agar. It grows as waxy, pigmented, cerebriform colonies 3 to 5 days following incubation.3 The bacterium can be difficult to culture, and it is important to notify the microbiology laboratory if there is a high index of clinical suspicion for infection.
A history of exposure to gardening or handling animals can increase the risk for an individual contracting Nocardia.3 Although nocardiosis can be found across the world, it is native to tropical and subtropical climates such as those found in India, Africa, Latin America, and Southeast Asia.1 Infections mostly are observed in individuals aged 20 to 40 years and tend to affect men more than women. Lesions typically are seen on the lower extremities, but localized infections also can be found on the torso, neck, and upper extremities.1
Cutaneous nocardiosis is a granulomatous infection encompassing both cutaneous and subcutaneous tissue, which ultimately can lead to injury of bone and viscera.1 Primary cutaneous nocardiosis can manifest as tumors or nodules that have a sporotrichoid pattern, in which they ascend along the lymphatics. Histopathology of infected tissue frequently shows a subcutaneous dermal infiltrate of neutrophils accompanied with abscess formation, and everlasting lesions may show signs of chronic inflammation and nonspecific granulomas.3
Treatment of nocardiosis should be guided by in vitro susceptibility tests. Sulfamethoxazole-trimethoprim 800 mg/160 mg taken as 1 tablet twice daily is the first-line option. The treatment duration is contingent on the extent, severity, and complications of infection but typically is 3 to 6 months.1
The Diagnosis: Cutaneous Nocardiosis
The wound culture was positive for Nocardia farcinica. The patient received a 5-day course of intravenous sulfamethoxazole-trimethoprim in the hospital and was transitioned to oral sulfamethoxazoletrimethoprim (800 mg/160 mg taken as 1 tablet twice daily) for 6 months. Complete resolution of the infection was noted at 6-month follow-up (Figure).
Nocardia is a gram-positive, aerobic bacterium that typically is found in soil, water, and decaying organic matter.1 There are more than 50 species; N farcinica, Nocardia nova, and Nocardia asteroides are the leading causes of infection in humans and animals. Nocardia asteroides is the most common cause of infection in humans.1,2 Nocardiosis is an uncommon opportunistic infection that usually targets the skin, lungs, and central nervous system.3 Although it mainly affects individuals who are immunocompromised, up to 30% of infections can be seen in immunocompetent hosts who can contract cutaneous nocardiosis after experiencing traumatic injury to the skin.1
Nocardiosis is difficult to diagnose due to its diverse clinical presentations. For example, cutaneous nocardiosis can manifest similar to mycetoma, sporotrichosis, spider bites, nontuberculous mycobacteria such as Mycobacterium marinum, or methicillin-resistant Staphylococcus aureus infections, thus making cutaneous nocardiosis one of the great imitators.1 A culture is required for definitive diagnosis, as Nocardia grows well on nonselective media such as blood or Löwenstein-Jensen agar. It grows as waxy, pigmented, cerebriform colonies 3 to 5 days following incubation.3 The bacterium can be difficult to culture, and it is important to notify the microbiology laboratory if there is a high index of clinical suspicion for infection.
A history of exposure to gardening or handling animals can increase the risk for an individual contracting Nocardia.3 Although nocardiosis can be found across the world, it is native to tropical and subtropical climates such as those found in India, Africa, Latin America, and Southeast Asia.1 Infections mostly are observed in individuals aged 20 to 40 years and tend to affect men more than women. Lesions typically are seen on the lower extremities, but localized infections also can be found on the torso, neck, and upper extremities.1
Cutaneous nocardiosis is a granulomatous infection encompassing both cutaneous and subcutaneous tissue, which ultimately can lead to injury of bone and viscera.1 Primary cutaneous nocardiosis can manifest as tumors or nodules that have a sporotrichoid pattern, in which they ascend along the lymphatics. Histopathology of infected tissue frequently shows a subcutaneous dermal infiltrate of neutrophils accompanied with abscess formation, and everlasting lesions may show signs of chronic inflammation and nonspecific granulomas.3
Treatment of nocardiosis should be guided by in vitro susceptibility tests. Sulfamethoxazole-trimethoprim 800 mg/160 mg taken as 1 tablet twice daily is the first-line option. The treatment duration is contingent on the extent, severity, and complications of infection but typically is 3 to 6 months.1
- Yu Q, Song J, Liu Y, et al. Progressive primary cutaneous nocardiosis in an immunocompetent patient. Cutis. 2023;111:E22-E25.
- Gaines RJ, Randall CJ, Ruland RT. Lymphocutaneous nocardiosis from commercially treated lumber: a case report. Cutis. 2006;78:249-251.
- Riswold KJ, Tjarks BJ, Kerkvliet AM. Cutaneous nocardiosis in an immunocompromised patient. Cutis. 2019;104:226-229.
- Yu Q, Song J, Liu Y, et al. Progressive primary cutaneous nocardiosis in an immunocompetent patient. Cutis. 2023;111:E22-E25.
- Gaines RJ, Randall CJ, Ruland RT. Lymphocutaneous nocardiosis from commercially treated lumber: a case report. Cutis. 2006;78:249-251.
- Riswold KJ, Tjarks BJ, Kerkvliet AM. Cutaneous nocardiosis in an immunocompromised patient. Cutis. 2019;104:226-229.
A 67-year-old man presented to the emergency department with a draining nodule on the right hand of 4 days’ duration. He reported that the swelling and redness started 1 hour after handling a succulent plant. The following day, the nodule increased in size and exudated yellow pus. He presented with swelling of the thumb and hand, which resulted in a decreased range of motion. He had a history of prediabetes and denied any recent travel, allergies, or animal exposures. Physical examination revealed a draining nodule on the dorsal aspect of the right hand that measured approximately 15×15 mm with surrounding erythema and tenderness. There also was progression of ascending erythema up to the axilla. The patient was admitted to the hospital.
Weight Loss Drugs Cut Cancer Risk in Diabetes Patients
Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage:
That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.
For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.
The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.
Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.
But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.
While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.
A version of this article appeared on WebMD.com.
Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage:
That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.
For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.
The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.
Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.
But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.
While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.
A version of this article appeared on WebMD.com.
Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage:
That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.
For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.
The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.
Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.
But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.
While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.
A version of this article appeared on WebMD.com.
Feds May End Hospital System’s Noncompete Contract for Part-Time Docs
Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB).
The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.
according to a copy of the terms included in NLRB’s June 18 complaint.
By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.
Mount Sinai did not respond to requests for comment.
The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.
“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”
Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing.
A Physician Blows the Whistle
An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system.
To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms.
The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release.
NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out.
In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices.
“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release.
Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.”
Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.
A version of this article first appeared on Medscape.com.
Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB).
The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.
according to a copy of the terms included in NLRB’s June 18 complaint.
By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.
Mount Sinai did not respond to requests for comment.
The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.
“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”
Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing.
A Physician Blows the Whistle
An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system.
To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms.
The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release.
NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out.
In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices.
“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release.
Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.”
Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.
A version of this article first appeared on Medscape.com.
Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB).
The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.
according to a copy of the terms included in NLRB’s June 18 complaint.
By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.
Mount Sinai did not respond to requests for comment.
The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.
“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”
Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing.
A Physician Blows the Whistle
An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system.
To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms.
The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release.
NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out.
In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices.
“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release.
Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.”
Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.
A version of this article first appeared on Medscape.com.
Histiocytoid Pyoderma Gangrenosum: A Challenging Case With Features of Sweet Syndrome
To the Editor:
Neutrophilic dermatoses—a group of inflammatory cutaneous conditions—include acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and neutrophilic dermatosis of the dorsal hands. Histopathology shows a dense dermal infiltrate of mature neutrophils. In 2005, the histiocytoid subtype of Sweet syndrome was introduced with histopathologic findings of a dermal infiltrate composed of immature myeloid cells that resemble histiocytes in appearance but stain strongly with neutrophil markers on immunohistochemistry.1 We present a case of histiocytoid pyoderma gangrenosum with histopathology that showed a dense dermal histiocytoid infiltrate with strong positivity for neutrophil markers on immunohistochemistry.
An 85-year-old man was seen by dermatology in the inpatient setting for a new-onset painful abdominal wound. He had a medical history of myelodysplastic syndrome (MDS), high-grade invasive papillary urothelial carcinoma of the bladder, and a recent diagnosis of low-grade invasive ascending colon adenocarcinoma. Ten days prior he underwent a right colectomy without intraoperative complications that was followed by septic shock. Workup with urinalysis and urine culture showed minimal pyuria with Pseudomonas aeruginosa. Additional studies, including blood cultures, abdominal wound cultures, computed tomography of the abdomen and pelvis, renal ultrasound, and chest radiographs, were unremarkable and showed no signs of surgical site infection, intra-abdominal or pelvic abscess formation, or pulmonary embolism. Broad-spectrum antibiotics—vancomycin and piperacillin-tazobactam—were started. Persistent fever (Tmax of 102.3 °F [39.1 °C]) and leukocytosis (45.3×109/L [4.2–10×109/L]) despite antibiotic therapy, increasing pressor requirements, and progressive painful erythema and purulence at the abdominal surgical site led to debridement of the wound by the general surgery team on day 9 following the initial surgery due to suspected necrotizing infection. Within 24 hours, dermatology was consulted for continued rapid expansion of the wound. Physical examination of the abdomen revealed a large, well-demarcated, pink-red, indurated, ulcerated plaque with clear to purulent exudate and superficial erosions with violaceous undermined borders extending centrifugally from the abdominal surgical incision line (Figure 1A). Two punch biopsies sent for histopathologic evaluation and tissue culture showed dermal edema with a dense histiocytic infiltrate with nodular foci and admixed mature neutrophils to a lesser degree (Figure 2). Special staining was negative for bacteria, fungi, and mycobacteria. Immunohistochemistry revealed positive staining of the dermal inflammatory infiltrate with CD68, myeloperoxidase, and lysozyme, as well as negative staining with CD34 (Figure 3). These findings were suggestive of a histiocytoid neutrophilic dermatosis such as Sweet syndrome or pyoderma gangrenosum. Due to the morphology of the solitary lesion and the abrupt exacerbation shortly after surgical intervention, the patient was diagnosed with histiocytoid pyoderma gangrenosum. At the same time, the patient’s septic shock was treated with intravenous hydrocortisone (100 mg 3 times daily) for 2 days and also achieved a prompt response in the cutaneous symptoms (Figure 1B).
Sweet syndrome and pyoderma gangrenosum are considered distinct neutrophilic dermatoses that rarely coexist but share several clinical and histopathologic features, which can become a diagnostic challenge.2 Both conditions can manifest clinically as abrupt-onset, tender, erythematous papules; vesiculopustular lesions; or bullae with ulcerative changes. They also exhibit pathergy; present with systemic symptoms such as pyrexia, malaise, and joint pain; are associated with underlying systemic conditions such as infections and/or malignancy; demonstrate a dense neutrophilic infiltrate in the dermis on histopathology; and respond promptly to systemic corticosteroids.2-6 Bullous Sweet syndrome, which can present as vesicles, pustules, or bullae that progress to superficial ulcerations, may represent a variant of neutrophilic dermatosis characterized by features seen in both Sweet syndrome and pyoderma gangrenosum, suggesting that these 2 conditions may be on a spectrum.5Clinical features such as erythema with a blue, gray, or purple hue; undermined and ragged borders; and healing of skin lesions with atrophic or cribriform scarring may favor pyoderma gangrenosum, whereas a dull red or plum color and resolution of lesions without scarring may support the diagnosis of Sweet syndrome.7 Although both conditions can exhibit pathergy secondary to minor skin trauma such as venipuncture and biopsies,2,3,5,8 Sweet syndrome rarely has been described to develop after surgery in a patient without a known history of the condition.9 In contrast, postsurgical pyoderma gangrenosum has been well described as secondary to the pathergy phenomenon.5
Our patient was favored to have pyoderma gangrenosum given the solitary lesion, its abrupt development after surgery, and the morphology of the lesion that exhibited a large violaceous to red ulcerative and exudative plaque with undermined borders with atrophic scarring. In patients with skin disease that cannot be distinguished with certainty as either Sweet syndrome or pyoderma gangrenosum, it is essential to recognize that, as neutrophilic dermatoses, both conditions can be managed with either the first-line treatment option of high-dose systemic steroids or one of the shared alternative first-line or second-line steroid-sparing treatments, such as dapsone and cyclosporine.2
Although the exact pathogenesis of pyoderma gangrenosum remains to be fully understood, paraneoplastic pyoderma gangrenosum is a frequently described phenomenon.10,11 Our patient’s history of multiple malignancies, both solid and hematologic, supports the likelihood of malignancy-induced pyoderma gangrenosum; however, given his history of MDS, several other conditions were ruled out prior to making the diagnosis of pyoderma gangrenosum.
Classically, neutrophilic dermatoses such as pyoderma gangrenosum have a dense dermal neutrophilic infiltrate. Concurrent myeloproliferative disorders can alter the maturation of leukocytes, subsequently leading to an atypical appearance of the inflammatory cells on histopathology. Further, in the setting of myeloproliferative disorders, conditions such as leukemia cutis, in which there can be a cutaneous infiltrate of immature or mature myeloid or lymphocytic cells, must be considered. To ensure our patient’s abdominal skin changes were not a cutaneous manifestation of hematologic malignancy, immunohistochemical staining with CD20 and CD3 was performed and showed only the rare presence of B and T lymphocytes, respectively. Staining with CD34 for lymphocytic and myeloid progenitor cells was negative in the dermal infiltrate and further reduced the likelihood of leukemia cutis. Alternatively, patients can have aleukemic cutaneous myeloid sarcoma or leukemia cutis without an underlying hematologic condition or with latent peripheral blood or bone marrow myeloproliferative disorder, but our patient’s history of MDS eliminated this possibility.12 After exclusion of cutaneous infiltration by malignant leukocytes, our patient was diagnosed with histiocytoid neutrophilic dermatosis.
Multiple reports have described histiocytoid Sweet syndrome, in which there is a dense dermal histiocytoid infiltrate on histopathology that demonstrates myeloid lineage with immunologic staining.1,13 The typical pattern of histiocytoid Sweet syndrome includes a predominantly unaffected epidermis with papillary dermal edema, an absence of vasculitis, and a dense dermal infiltrate primarily composed of immature histiocytelike mononuclear cells with a basophilic elongated, twisted, or kidney-shaped nucleus and pale eosinophilic cytoplasm.1,13 In an analogous manner, Morin et al12 described a patient with congenital hypogammaglobulinemia who presented with lesions that clinically resembled pyoderma gangrenosum but revealed a dense dermal infiltrate mostly made of large immature histiocytoid mononuclear cells on histopathology, consistent with the histopathologic features observed in histiocytoid Sweet syndrome. The patient ultimately was diagnosed with histiocytoid pyoderma gangrenosum. Similarly, we believe that our patient also developed histiocytoid pyoderma gangrenosum. As with histiocytoid Sweet syndrome, this diagnosis is based on histopathologic and immunohistochemical findings of a dense dermal infiltrate composed of histiocyte-resembling immature neutrophils.
Typically, pyoderma gangrenosum responds promptly to treatment with systemic corticosteroids.4 Steroid-sparing agents such as cyclosporine, azathioprine, dapsone, and tumor necrosis factor α inhibitors also may be used.4,10 In the setting of MDS, clearance of pyoderma gangrenosum has been reported upon treatment of the underlying malignancy,14 high-dose systemic corticosteroids,11,15 cyclosporine with systemic steroids,16 thalidomide,17 combination therapy with thalidomide and interferon alfa-2a,18 and ustekinumab with vacuum-assisted closure therapy.19 Our patient’s histiocytoid pyoderma gangrenosum in the setting of solid and hematologic malignancy cleared rapidly with high-dose systemic hydrocortisone.
In the setting of malignancy, as in our patient, neutrophilic dermatoses may develop from an aberrant immune system or tumor-induced cytokine dysregulation that leads to increased neutrophil production or dysfunction.4,10,11 Although our patient’s MDS may have contributed to the atypical appearance of the dermal inflammatory infiltrate, it is unclear whether the hematologic disorder increased his risk for the histiocytoid variant of neutrophilic dermatoses. Alegría-Landa et al13 reported that histiocytoid Sweet syndrome is associated with hematologic malignancy at a similar frequency as classic Sweet syndrome. It is unknown if histiocytoid pyoderma gangrenosum would have a strong association with hematologic malignancy. Future reports may elucidate a better understanding of the histiocytoid subtype of pyoderma gangrenosum and its clinical implications.
- Requena L, Kutzner H, Palmedo G, et al. Histiocytoid Sweet syndrome: a dermal infiltration of immature neutrophilic granulocytes. Arch Dermatol. 2005;141:834-842.
- Cohen PR. Neutrophilic dermatoses: a review of current treatment options. Am J Clin Dermatol. 2009;10:301-312.
- Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
- Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol. 2015;73:691-698.
- Wallach D, Vignon-Pennamen MD. Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses. Br J Dermatol. 2018;178:595-602.
- Walling HW, Snipes CJ, Gerami P, et al. The relationship between neutrophilic dermatosis of the dorsal hands and Sweet syndrome: report of 9 cases and comparison to atypical pyoderma gangrenosum. Arch Dermatol. 2006;142:57-63.
- Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet’s syndrome. Postgrad Med. 1997;73:65-68.
- Nelson CA, Stephen S, Ashchyan HJ, et al. Neutrophilic dermatoses: pathogenesis, Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet disease. J Am Acad Dermatol. 2018;79:987-1006.
- Minocha R, Sebaratnam DF, Choi JY. Sweet’s syndrome following surgery: cutaneous trauma as a possible aetiological co-factor in neutrophilic dermatoses. Australas J Dermatol. 2015;56:E74-E76.
- Shah M, Sachdeva M, Gefri A, et al. Paraneoplastic pyoderma gangrenosum in solid organ malignancy: a literature review. Int J Dermatol. 2020;59:154-158.
- Montagnon CM, Fracica EA, Patel AA, et al. Pyoderma gangrenosum in hematologic malignancies: a systematic review. J Am Acad Dermatol. 2020;82:1346-1359.
- Morin CB, Côté B, Belisle A. An interesting case of pyoderma gangrenosum with immature histiocytoid neutrophils. J Cutan Pathol. 2018;45:63-66.
- Alegría-Landa V, Rodríguez-Pinilla SM, Santos-Briz A, et al. Clinicopathologic, immunohistochemical, and molecular features of histiocytoid Sweet syndrome. JAMA Dermatol. 2017;153:651-659.
- Saleh MFM, Saunthararajah Y. Severe pyoderma gangrenosum caused by myelodysplastic syndrome successfully treated with decitabine administered by a noncytotoxic regimen. Clin Case Rep. 2017;5:2025-2027.
- Yamauchi R, Ishida K, Iwashima Y, et al. Successful treatment of pyoderma gangrenosum that developed in a patient with myelodysplastic syndrome. J Infect Chemother. 2003;9:268-271.
- Ha JW, Hahm JE, Kim KS, et al. A case of pyoderma gangrenosum with myelodysplastic syndrome. Ann Dermatol. 2018;30:392-393.
- Malkan UY, Gunes G, Eliacik E, et al. Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome case. Int J Med Case Rep. 2016;9:61-64.
- Koca E, Duman AE, Cetiner D, et al. Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum. Neth J Med. 2006;64:422-424.
- Nieto D, Sendagorta E, Rueda JM, et al. Successful treatment with ustekinumab and vacuum-assisted closure therapy in recalcitrant myelodysplastic syndrome-associated pyoderma gangrenosum: case report and literature review. Clin Exp Dermatol. 2019;44:116-119.
To the Editor:
Neutrophilic dermatoses—a group of inflammatory cutaneous conditions—include acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and neutrophilic dermatosis of the dorsal hands. Histopathology shows a dense dermal infiltrate of mature neutrophils. In 2005, the histiocytoid subtype of Sweet syndrome was introduced with histopathologic findings of a dermal infiltrate composed of immature myeloid cells that resemble histiocytes in appearance but stain strongly with neutrophil markers on immunohistochemistry.1 We present a case of histiocytoid pyoderma gangrenosum with histopathology that showed a dense dermal histiocytoid infiltrate with strong positivity for neutrophil markers on immunohistochemistry.
An 85-year-old man was seen by dermatology in the inpatient setting for a new-onset painful abdominal wound. He had a medical history of myelodysplastic syndrome (MDS), high-grade invasive papillary urothelial carcinoma of the bladder, and a recent diagnosis of low-grade invasive ascending colon adenocarcinoma. Ten days prior he underwent a right colectomy without intraoperative complications that was followed by septic shock. Workup with urinalysis and urine culture showed minimal pyuria with Pseudomonas aeruginosa. Additional studies, including blood cultures, abdominal wound cultures, computed tomography of the abdomen and pelvis, renal ultrasound, and chest radiographs, were unremarkable and showed no signs of surgical site infection, intra-abdominal or pelvic abscess formation, or pulmonary embolism. Broad-spectrum antibiotics—vancomycin and piperacillin-tazobactam—were started. Persistent fever (Tmax of 102.3 °F [39.1 °C]) and leukocytosis (45.3×109/L [4.2–10×109/L]) despite antibiotic therapy, increasing pressor requirements, and progressive painful erythema and purulence at the abdominal surgical site led to debridement of the wound by the general surgery team on day 9 following the initial surgery due to suspected necrotizing infection. Within 24 hours, dermatology was consulted for continued rapid expansion of the wound. Physical examination of the abdomen revealed a large, well-demarcated, pink-red, indurated, ulcerated plaque with clear to purulent exudate and superficial erosions with violaceous undermined borders extending centrifugally from the abdominal surgical incision line (Figure 1A). Two punch biopsies sent for histopathologic evaluation and tissue culture showed dermal edema with a dense histiocytic infiltrate with nodular foci and admixed mature neutrophils to a lesser degree (Figure 2). Special staining was negative for bacteria, fungi, and mycobacteria. Immunohistochemistry revealed positive staining of the dermal inflammatory infiltrate with CD68, myeloperoxidase, and lysozyme, as well as negative staining with CD34 (Figure 3). These findings were suggestive of a histiocytoid neutrophilic dermatosis such as Sweet syndrome or pyoderma gangrenosum. Due to the morphology of the solitary lesion and the abrupt exacerbation shortly after surgical intervention, the patient was diagnosed with histiocytoid pyoderma gangrenosum. At the same time, the patient’s septic shock was treated with intravenous hydrocortisone (100 mg 3 times daily) for 2 days and also achieved a prompt response in the cutaneous symptoms (Figure 1B).
Sweet syndrome and pyoderma gangrenosum are considered distinct neutrophilic dermatoses that rarely coexist but share several clinical and histopathologic features, which can become a diagnostic challenge.2 Both conditions can manifest clinically as abrupt-onset, tender, erythematous papules; vesiculopustular lesions; or bullae with ulcerative changes. They also exhibit pathergy; present with systemic symptoms such as pyrexia, malaise, and joint pain; are associated with underlying systemic conditions such as infections and/or malignancy; demonstrate a dense neutrophilic infiltrate in the dermis on histopathology; and respond promptly to systemic corticosteroids.2-6 Bullous Sweet syndrome, which can present as vesicles, pustules, or bullae that progress to superficial ulcerations, may represent a variant of neutrophilic dermatosis characterized by features seen in both Sweet syndrome and pyoderma gangrenosum, suggesting that these 2 conditions may be on a spectrum.5Clinical features such as erythema with a blue, gray, or purple hue; undermined and ragged borders; and healing of skin lesions with atrophic or cribriform scarring may favor pyoderma gangrenosum, whereas a dull red or plum color and resolution of lesions without scarring may support the diagnosis of Sweet syndrome.7 Although both conditions can exhibit pathergy secondary to minor skin trauma such as venipuncture and biopsies,2,3,5,8 Sweet syndrome rarely has been described to develop after surgery in a patient without a known history of the condition.9 In contrast, postsurgical pyoderma gangrenosum has been well described as secondary to the pathergy phenomenon.5
Our patient was favored to have pyoderma gangrenosum given the solitary lesion, its abrupt development after surgery, and the morphology of the lesion that exhibited a large violaceous to red ulcerative and exudative plaque with undermined borders with atrophic scarring. In patients with skin disease that cannot be distinguished with certainty as either Sweet syndrome or pyoderma gangrenosum, it is essential to recognize that, as neutrophilic dermatoses, both conditions can be managed with either the first-line treatment option of high-dose systemic steroids or one of the shared alternative first-line or second-line steroid-sparing treatments, such as dapsone and cyclosporine.2
Although the exact pathogenesis of pyoderma gangrenosum remains to be fully understood, paraneoplastic pyoderma gangrenosum is a frequently described phenomenon.10,11 Our patient’s history of multiple malignancies, both solid and hematologic, supports the likelihood of malignancy-induced pyoderma gangrenosum; however, given his history of MDS, several other conditions were ruled out prior to making the diagnosis of pyoderma gangrenosum.
Classically, neutrophilic dermatoses such as pyoderma gangrenosum have a dense dermal neutrophilic infiltrate. Concurrent myeloproliferative disorders can alter the maturation of leukocytes, subsequently leading to an atypical appearance of the inflammatory cells on histopathology. Further, in the setting of myeloproliferative disorders, conditions such as leukemia cutis, in which there can be a cutaneous infiltrate of immature or mature myeloid or lymphocytic cells, must be considered. To ensure our patient’s abdominal skin changes were not a cutaneous manifestation of hematologic malignancy, immunohistochemical staining with CD20 and CD3 was performed and showed only the rare presence of B and T lymphocytes, respectively. Staining with CD34 for lymphocytic and myeloid progenitor cells was negative in the dermal infiltrate and further reduced the likelihood of leukemia cutis. Alternatively, patients can have aleukemic cutaneous myeloid sarcoma or leukemia cutis without an underlying hematologic condition or with latent peripheral blood or bone marrow myeloproliferative disorder, but our patient’s history of MDS eliminated this possibility.12 After exclusion of cutaneous infiltration by malignant leukocytes, our patient was diagnosed with histiocytoid neutrophilic dermatosis.
Multiple reports have described histiocytoid Sweet syndrome, in which there is a dense dermal histiocytoid infiltrate on histopathology that demonstrates myeloid lineage with immunologic staining.1,13 The typical pattern of histiocytoid Sweet syndrome includes a predominantly unaffected epidermis with papillary dermal edema, an absence of vasculitis, and a dense dermal infiltrate primarily composed of immature histiocytelike mononuclear cells with a basophilic elongated, twisted, or kidney-shaped nucleus and pale eosinophilic cytoplasm.1,13 In an analogous manner, Morin et al12 described a patient with congenital hypogammaglobulinemia who presented with lesions that clinically resembled pyoderma gangrenosum but revealed a dense dermal infiltrate mostly made of large immature histiocytoid mononuclear cells on histopathology, consistent with the histopathologic features observed in histiocytoid Sweet syndrome. The patient ultimately was diagnosed with histiocytoid pyoderma gangrenosum. Similarly, we believe that our patient also developed histiocytoid pyoderma gangrenosum. As with histiocytoid Sweet syndrome, this diagnosis is based on histopathologic and immunohistochemical findings of a dense dermal infiltrate composed of histiocyte-resembling immature neutrophils.
Typically, pyoderma gangrenosum responds promptly to treatment with systemic corticosteroids.4 Steroid-sparing agents such as cyclosporine, azathioprine, dapsone, and tumor necrosis factor α inhibitors also may be used.4,10 In the setting of MDS, clearance of pyoderma gangrenosum has been reported upon treatment of the underlying malignancy,14 high-dose systemic corticosteroids,11,15 cyclosporine with systemic steroids,16 thalidomide,17 combination therapy with thalidomide and interferon alfa-2a,18 and ustekinumab with vacuum-assisted closure therapy.19 Our patient’s histiocytoid pyoderma gangrenosum in the setting of solid and hematologic malignancy cleared rapidly with high-dose systemic hydrocortisone.
In the setting of malignancy, as in our patient, neutrophilic dermatoses may develop from an aberrant immune system or tumor-induced cytokine dysregulation that leads to increased neutrophil production or dysfunction.4,10,11 Although our patient’s MDS may have contributed to the atypical appearance of the dermal inflammatory infiltrate, it is unclear whether the hematologic disorder increased his risk for the histiocytoid variant of neutrophilic dermatoses. Alegría-Landa et al13 reported that histiocytoid Sweet syndrome is associated with hematologic malignancy at a similar frequency as classic Sweet syndrome. It is unknown if histiocytoid pyoderma gangrenosum would have a strong association with hematologic malignancy. Future reports may elucidate a better understanding of the histiocytoid subtype of pyoderma gangrenosum and its clinical implications.
To the Editor:
Neutrophilic dermatoses—a group of inflammatory cutaneous conditions—include acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and neutrophilic dermatosis of the dorsal hands. Histopathology shows a dense dermal infiltrate of mature neutrophils. In 2005, the histiocytoid subtype of Sweet syndrome was introduced with histopathologic findings of a dermal infiltrate composed of immature myeloid cells that resemble histiocytes in appearance but stain strongly with neutrophil markers on immunohistochemistry.1 We present a case of histiocytoid pyoderma gangrenosum with histopathology that showed a dense dermal histiocytoid infiltrate with strong positivity for neutrophil markers on immunohistochemistry.
An 85-year-old man was seen by dermatology in the inpatient setting for a new-onset painful abdominal wound. He had a medical history of myelodysplastic syndrome (MDS), high-grade invasive papillary urothelial carcinoma of the bladder, and a recent diagnosis of low-grade invasive ascending colon adenocarcinoma. Ten days prior he underwent a right colectomy without intraoperative complications that was followed by septic shock. Workup with urinalysis and urine culture showed minimal pyuria with Pseudomonas aeruginosa. Additional studies, including blood cultures, abdominal wound cultures, computed tomography of the abdomen and pelvis, renal ultrasound, and chest radiographs, were unremarkable and showed no signs of surgical site infection, intra-abdominal or pelvic abscess formation, or pulmonary embolism. Broad-spectrum antibiotics—vancomycin and piperacillin-tazobactam—were started. Persistent fever (Tmax of 102.3 °F [39.1 °C]) and leukocytosis (45.3×109/L [4.2–10×109/L]) despite antibiotic therapy, increasing pressor requirements, and progressive painful erythema and purulence at the abdominal surgical site led to debridement of the wound by the general surgery team on day 9 following the initial surgery due to suspected necrotizing infection. Within 24 hours, dermatology was consulted for continued rapid expansion of the wound. Physical examination of the abdomen revealed a large, well-demarcated, pink-red, indurated, ulcerated plaque with clear to purulent exudate and superficial erosions with violaceous undermined borders extending centrifugally from the abdominal surgical incision line (Figure 1A). Two punch biopsies sent for histopathologic evaluation and tissue culture showed dermal edema with a dense histiocytic infiltrate with nodular foci and admixed mature neutrophils to a lesser degree (Figure 2). Special staining was negative for bacteria, fungi, and mycobacteria. Immunohistochemistry revealed positive staining of the dermal inflammatory infiltrate with CD68, myeloperoxidase, and lysozyme, as well as negative staining with CD34 (Figure 3). These findings were suggestive of a histiocytoid neutrophilic dermatosis such as Sweet syndrome or pyoderma gangrenosum. Due to the morphology of the solitary lesion and the abrupt exacerbation shortly after surgical intervention, the patient was diagnosed with histiocytoid pyoderma gangrenosum. At the same time, the patient’s septic shock was treated with intravenous hydrocortisone (100 mg 3 times daily) for 2 days and also achieved a prompt response in the cutaneous symptoms (Figure 1B).
Sweet syndrome and pyoderma gangrenosum are considered distinct neutrophilic dermatoses that rarely coexist but share several clinical and histopathologic features, which can become a diagnostic challenge.2 Both conditions can manifest clinically as abrupt-onset, tender, erythematous papules; vesiculopustular lesions; or bullae with ulcerative changes. They also exhibit pathergy; present with systemic symptoms such as pyrexia, malaise, and joint pain; are associated with underlying systemic conditions such as infections and/or malignancy; demonstrate a dense neutrophilic infiltrate in the dermis on histopathology; and respond promptly to systemic corticosteroids.2-6 Bullous Sweet syndrome, which can present as vesicles, pustules, or bullae that progress to superficial ulcerations, may represent a variant of neutrophilic dermatosis characterized by features seen in both Sweet syndrome and pyoderma gangrenosum, suggesting that these 2 conditions may be on a spectrum.5Clinical features such as erythema with a blue, gray, or purple hue; undermined and ragged borders; and healing of skin lesions with atrophic or cribriform scarring may favor pyoderma gangrenosum, whereas a dull red or plum color and resolution of lesions without scarring may support the diagnosis of Sweet syndrome.7 Although both conditions can exhibit pathergy secondary to minor skin trauma such as venipuncture and biopsies,2,3,5,8 Sweet syndrome rarely has been described to develop after surgery in a patient without a known history of the condition.9 In contrast, postsurgical pyoderma gangrenosum has been well described as secondary to the pathergy phenomenon.5
Our patient was favored to have pyoderma gangrenosum given the solitary lesion, its abrupt development after surgery, and the morphology of the lesion that exhibited a large violaceous to red ulcerative and exudative plaque with undermined borders with atrophic scarring. In patients with skin disease that cannot be distinguished with certainty as either Sweet syndrome or pyoderma gangrenosum, it is essential to recognize that, as neutrophilic dermatoses, both conditions can be managed with either the first-line treatment option of high-dose systemic steroids or one of the shared alternative first-line or second-line steroid-sparing treatments, such as dapsone and cyclosporine.2
Although the exact pathogenesis of pyoderma gangrenosum remains to be fully understood, paraneoplastic pyoderma gangrenosum is a frequently described phenomenon.10,11 Our patient’s history of multiple malignancies, both solid and hematologic, supports the likelihood of malignancy-induced pyoderma gangrenosum; however, given his history of MDS, several other conditions were ruled out prior to making the diagnosis of pyoderma gangrenosum.
Classically, neutrophilic dermatoses such as pyoderma gangrenosum have a dense dermal neutrophilic infiltrate. Concurrent myeloproliferative disorders can alter the maturation of leukocytes, subsequently leading to an atypical appearance of the inflammatory cells on histopathology. Further, in the setting of myeloproliferative disorders, conditions such as leukemia cutis, in which there can be a cutaneous infiltrate of immature or mature myeloid or lymphocytic cells, must be considered. To ensure our patient’s abdominal skin changes were not a cutaneous manifestation of hematologic malignancy, immunohistochemical staining with CD20 and CD3 was performed and showed only the rare presence of B and T lymphocytes, respectively. Staining with CD34 for lymphocytic and myeloid progenitor cells was negative in the dermal infiltrate and further reduced the likelihood of leukemia cutis. Alternatively, patients can have aleukemic cutaneous myeloid sarcoma or leukemia cutis without an underlying hematologic condition or with latent peripheral blood or bone marrow myeloproliferative disorder, but our patient’s history of MDS eliminated this possibility.12 After exclusion of cutaneous infiltration by malignant leukocytes, our patient was diagnosed with histiocytoid neutrophilic dermatosis.
Multiple reports have described histiocytoid Sweet syndrome, in which there is a dense dermal histiocytoid infiltrate on histopathology that demonstrates myeloid lineage with immunologic staining.1,13 The typical pattern of histiocytoid Sweet syndrome includes a predominantly unaffected epidermis with papillary dermal edema, an absence of vasculitis, and a dense dermal infiltrate primarily composed of immature histiocytelike mononuclear cells with a basophilic elongated, twisted, or kidney-shaped nucleus and pale eosinophilic cytoplasm.1,13 In an analogous manner, Morin et al12 described a patient with congenital hypogammaglobulinemia who presented with lesions that clinically resembled pyoderma gangrenosum but revealed a dense dermal infiltrate mostly made of large immature histiocytoid mononuclear cells on histopathology, consistent with the histopathologic features observed in histiocytoid Sweet syndrome. The patient ultimately was diagnosed with histiocytoid pyoderma gangrenosum. Similarly, we believe that our patient also developed histiocytoid pyoderma gangrenosum. As with histiocytoid Sweet syndrome, this diagnosis is based on histopathologic and immunohistochemical findings of a dense dermal infiltrate composed of histiocyte-resembling immature neutrophils.
Typically, pyoderma gangrenosum responds promptly to treatment with systemic corticosteroids.4 Steroid-sparing agents such as cyclosporine, azathioprine, dapsone, and tumor necrosis factor α inhibitors also may be used.4,10 In the setting of MDS, clearance of pyoderma gangrenosum has been reported upon treatment of the underlying malignancy,14 high-dose systemic corticosteroids,11,15 cyclosporine with systemic steroids,16 thalidomide,17 combination therapy with thalidomide and interferon alfa-2a,18 and ustekinumab with vacuum-assisted closure therapy.19 Our patient’s histiocytoid pyoderma gangrenosum in the setting of solid and hematologic malignancy cleared rapidly with high-dose systemic hydrocortisone.
In the setting of malignancy, as in our patient, neutrophilic dermatoses may develop from an aberrant immune system or tumor-induced cytokine dysregulation that leads to increased neutrophil production or dysfunction.4,10,11 Although our patient’s MDS may have contributed to the atypical appearance of the dermal inflammatory infiltrate, it is unclear whether the hematologic disorder increased his risk for the histiocytoid variant of neutrophilic dermatoses. Alegría-Landa et al13 reported that histiocytoid Sweet syndrome is associated with hematologic malignancy at a similar frequency as classic Sweet syndrome. It is unknown if histiocytoid pyoderma gangrenosum would have a strong association with hematologic malignancy. Future reports may elucidate a better understanding of the histiocytoid subtype of pyoderma gangrenosum and its clinical implications.
- Requena L, Kutzner H, Palmedo G, et al. Histiocytoid Sweet syndrome: a dermal infiltration of immature neutrophilic granulocytes. Arch Dermatol. 2005;141:834-842.
- Cohen PR. Neutrophilic dermatoses: a review of current treatment options. Am J Clin Dermatol. 2009;10:301-312.
- Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
- Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol. 2015;73:691-698.
- Wallach D, Vignon-Pennamen MD. Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses. Br J Dermatol. 2018;178:595-602.
- Walling HW, Snipes CJ, Gerami P, et al. The relationship between neutrophilic dermatosis of the dorsal hands and Sweet syndrome: report of 9 cases and comparison to atypical pyoderma gangrenosum. Arch Dermatol. 2006;142:57-63.
- Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet’s syndrome. Postgrad Med. 1997;73:65-68.
- Nelson CA, Stephen S, Ashchyan HJ, et al. Neutrophilic dermatoses: pathogenesis, Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet disease. J Am Acad Dermatol. 2018;79:987-1006.
- Minocha R, Sebaratnam DF, Choi JY. Sweet’s syndrome following surgery: cutaneous trauma as a possible aetiological co-factor in neutrophilic dermatoses. Australas J Dermatol. 2015;56:E74-E76.
- Shah M, Sachdeva M, Gefri A, et al. Paraneoplastic pyoderma gangrenosum in solid organ malignancy: a literature review. Int J Dermatol. 2020;59:154-158.
- Montagnon CM, Fracica EA, Patel AA, et al. Pyoderma gangrenosum in hematologic malignancies: a systematic review. J Am Acad Dermatol. 2020;82:1346-1359.
- Morin CB, Côté B, Belisle A. An interesting case of pyoderma gangrenosum with immature histiocytoid neutrophils. J Cutan Pathol. 2018;45:63-66.
- Alegría-Landa V, Rodríguez-Pinilla SM, Santos-Briz A, et al. Clinicopathologic, immunohistochemical, and molecular features of histiocytoid Sweet syndrome. JAMA Dermatol. 2017;153:651-659.
- Saleh MFM, Saunthararajah Y. Severe pyoderma gangrenosum caused by myelodysplastic syndrome successfully treated with decitabine administered by a noncytotoxic regimen. Clin Case Rep. 2017;5:2025-2027.
- Yamauchi R, Ishida K, Iwashima Y, et al. Successful treatment of pyoderma gangrenosum that developed in a patient with myelodysplastic syndrome. J Infect Chemother. 2003;9:268-271.
- Ha JW, Hahm JE, Kim KS, et al. A case of pyoderma gangrenosum with myelodysplastic syndrome. Ann Dermatol. 2018;30:392-393.
- Malkan UY, Gunes G, Eliacik E, et al. Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome case. Int J Med Case Rep. 2016;9:61-64.
- Koca E, Duman AE, Cetiner D, et al. Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum. Neth J Med. 2006;64:422-424.
- Nieto D, Sendagorta E, Rueda JM, et al. Successful treatment with ustekinumab and vacuum-assisted closure therapy in recalcitrant myelodysplastic syndrome-associated pyoderma gangrenosum: case report and literature review. Clin Exp Dermatol. 2019;44:116-119.
- Requena L, Kutzner H, Palmedo G, et al. Histiocytoid Sweet syndrome: a dermal infiltration of immature neutrophilic granulocytes. Arch Dermatol. 2005;141:834-842.
- Cohen PR. Neutrophilic dermatoses: a review of current treatment options. Am J Clin Dermatol. 2009;10:301-312.
- Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
- Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol. 2015;73:691-698.
- Wallach D, Vignon-Pennamen MD. Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses. Br J Dermatol. 2018;178:595-602.
- Walling HW, Snipes CJ, Gerami P, et al. The relationship between neutrophilic dermatosis of the dorsal hands and Sweet syndrome: report of 9 cases and comparison to atypical pyoderma gangrenosum. Arch Dermatol. 2006;142:57-63.
- Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet’s syndrome. Postgrad Med. 1997;73:65-68.
- Nelson CA, Stephen S, Ashchyan HJ, et al. Neutrophilic dermatoses: pathogenesis, Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet disease. J Am Acad Dermatol. 2018;79:987-1006.
- Minocha R, Sebaratnam DF, Choi JY. Sweet’s syndrome following surgery: cutaneous trauma as a possible aetiological co-factor in neutrophilic dermatoses. Australas J Dermatol. 2015;56:E74-E76.
- Shah M, Sachdeva M, Gefri A, et al. Paraneoplastic pyoderma gangrenosum in solid organ malignancy: a literature review. Int J Dermatol. 2020;59:154-158.
- Montagnon CM, Fracica EA, Patel AA, et al. Pyoderma gangrenosum in hematologic malignancies: a systematic review. J Am Acad Dermatol. 2020;82:1346-1359.
- Morin CB, Côté B, Belisle A. An interesting case of pyoderma gangrenosum with immature histiocytoid neutrophils. J Cutan Pathol. 2018;45:63-66.
- Alegría-Landa V, Rodríguez-Pinilla SM, Santos-Briz A, et al. Clinicopathologic, immunohistochemical, and molecular features of histiocytoid Sweet syndrome. JAMA Dermatol. 2017;153:651-659.
- Saleh MFM, Saunthararajah Y. Severe pyoderma gangrenosum caused by myelodysplastic syndrome successfully treated with decitabine administered by a noncytotoxic regimen. Clin Case Rep. 2017;5:2025-2027.
- Yamauchi R, Ishida K, Iwashima Y, et al. Successful treatment of pyoderma gangrenosum that developed in a patient with myelodysplastic syndrome. J Infect Chemother. 2003;9:268-271.
- Ha JW, Hahm JE, Kim KS, et al. A case of pyoderma gangrenosum with myelodysplastic syndrome. Ann Dermatol. 2018;30:392-393.
- Malkan UY, Gunes G, Eliacik E, et al. Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome case. Int J Med Case Rep. 2016;9:61-64.
- Koca E, Duman AE, Cetiner D, et al. Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum. Neth J Med. 2006;64:422-424.
- Nieto D, Sendagorta E, Rueda JM, et al. Successful treatment with ustekinumab and vacuum-assisted closure therapy in recalcitrant myelodysplastic syndrome-associated pyoderma gangrenosum: case report and literature review. Clin Exp Dermatol. 2019;44:116-119.
Practice Points:
- Dermatologists and dermatopathologists should be aware of the histiocytoid variant of pyoderma gangrenosum, which can clinical and histologic features that overlap with histiocytoid Sweet syndrome.
- When considering a diagnosis of histiocytoid neutrophilic dermatoses, leukemia cutis or aleukemic cutaneous myeloid sarcoma should be ruled out.
- Similar to histiocytoid Sweet syndrome and neutrophilic dermatoses in the setting of hematologic or solid organ malignancy, histiocytoid pyoderma gangrenosum may respond well to high-dose systemic corticosteroids.
Nail Alterations From Musical Instruments: Insights for Dermatologists Treating Musicians
A variety of skin problems can occur in musicians due to the repetitive movements of playing instruments.1,2 Musicians’ nails are continuously exposed to the mechanical forces and chemical substances characteristic of their instruments.3 Occupational nail alterations in musicians caused by repetitive physical trauma, allergic contact dermatitis, and/or infection may lead to disability and compromise their professional career.
We conducted a systematic review of the literature on the clinical features of musical instrument–related nail alterations to optimize the management and prevention of these conditions.
Methods
We conducted a systematic review of PubMed, Scopus, and Google Scholar databases for eligible publications on instrument-related nail alterations in musicians using the search terms musicians with nail, onychopathy, and Raynaud. No time or language criteria were applied. Reviews, editorials, and articles not related to the topic were excluded. Bibliographies/reference lists were checked to find any additional relevant publications. Relevant articles in English and French were screened by 2 independent reviewers (A.G. and N.L.), and the following data were extracted for qualitative synthesis: sex, age, musical instrument, clinical features, number of years practicing the instrument, laboratory investigations, and disease course.
Results
The literature search yielded 11 publications. Sixteen additional articles were identified by other methods (ie, references, related publications). Overall, 3 full-text articles described general nail alterations but did not describe the clinical data, and 11 publications were editorials, commentaries, reviews, or not relevant. Thirteen contributions fulfilled the inclusion criteria and were eligible for qualitative synthesis. The flow diagram illustrates the screening process (Figure 1).
Twenty-three patients were included. The instruments identified were divided into 2 groups: string instruments (ie, guitar, violin, harp) and percussion instruments (ie, drums, piano, slap bass). Nail alterations were clinically expressed as: (1) modifications of the nail surface; (2) nail bed, soft-tissue, and bone abnormalities; and (3) periungual tissue and distal pulp disorders. All cases are summarized in the Table.4-16 Three articles described occupational Raynaud phenomenon.12-14
Comment
Modifications of the Nail Surface—Onychodystrophy, such as deformity or discoloration of the nail plate, was described in 6 patients among a cohort of 295 musicians and an additional 6 patients among 199 musicians with induced skin lesions. This condition was most common in string instrument players and pianists due to injury and irritation.
One patient, who had been a professional violist for 27 years, presented with lamellar onychoschizia, which corresponds to a horizontal splitting of the nail toward its distal portion (Figure 2). The 3 fingernails of the dominant hand were involved with a V-shaped incision of the distal margin of the nail due to the repetitive friction of the nails with the strings.6
Striations of the nail plate were reported in a guitarist who played for 10 years.7 Physical examination revealed linear transverse ridges alternating with depressions on the central aspect of the nail plate of the right thumbnail, as the patient was right-handed. This condition, attributed to sustained pressure on the string applied by the thumb, also has been called habit tic deformity.7
Nail Bed, Soft-Tissue, and Bone Lesions—Purpura (or hemorrhage) of the nail bed was associated with a percussion instrument (ie, piano) in 1 patient, affecting the second, third, and fourth fingernails of the right hand.8 Especially when performing ascending glissando passages, the pianist applies pressure that may damage the finger and cause fingernail purpura. This condition improved after the patient stopping practicing glissandi.8
Three patients—2 guitarists and 1 violist—had onycholysis, defined by a loss of the attachment between the nail bed and the nail plate (Figure 3). It may result from repetitive trauma when strings are plucked.6,9,10
Acro-osteolysis associated with pain was reported in 2 guitarists.10,11 This condition is defined as transverse lytic bands in the distal phalanges (Figure 4). Acro-osteolysis may be secondary to multiple causes, such as vinyl chloride exposure, connective tissue diseases, thermal injuries, neuropathic diseases, hyperparathyroidism, nutritional deficiencies, psoriasis, and biomechanical stress.10 In musicians playing instruments, the mechanical stress to the guitar-playing fingers is the causative factor.17
Periungual Tissue and Distal Pulp Disorders—Paronychia is an important occupational hazard of harpists, violists, and pianists.2 It represents an inflammatory condition involving the folds of tissue surrounding fingernails. Pizzicato paronychia is related to infection in the nail fold in string players and secondary to pizzicato playing, whereby the musician plucks the instrument strings with the nails and fingertips.3
Acrylates in artificial nails frequently are used among guitarists to strengthen their nails. A case of occupational allergic contact dermatitis induced by acrylic gel nails in a flamenco guitarist was described.9 The patient developed dystrophy, onycholysis, and paronychia involving the nails of the right hand where acrylic materials were used, which resolved following the removal of the artificial nails. Patch tests were performed and were positive for 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, ethylene glycol dimethacrylate, and 2-hydroxypropyl methacrylate, supporting the diagnosis of allergic contact dermatitis to acrylates.9 Therefore, musicians should be aware of the sensitizing potential of acrylates and adopt preventive measures.
Unilateral Raynaud phenomenon of the dominant hand was noted in 3 cases of musicians who played string instruments due to the increased tendency to vasospasm in the digital capillaries from the direct transmission of vibrations of the strings (>100 Hz).12-14 Consequently, the disruption of the digital blood circulation leads to an abnormal reaction to cold, which is called vibration-induced white fingers or vasospastic white finger disease.19 In these 3 patients, capillaroscopy showed a nonspecific pattern with a lack of morphologic homogeneity of capillaries, the presence of enlarged capillaries, ectasia of the efferent tract of the loops, tortuous capillaries, local hemorrhages, and neoangiogenesis.13,14
A middle-aged professional concert pianist presented with paronychia with hyperkeratosis of the lateral nail fold. Histopathology revealed a subungual keratoacanthoma eroding the distal phalanx tip, which was removed by surgical excision. The repeated fingertip trauma associated with pianistic activity was suspected to be the causative event.16
Callosities also are common on the fingertips of musicians, including 18.4% of patients in a cohort of 628 musicians, and involving fingers in 64.6% of these patients.4 These callosities are explained by the chronic mechanical forces and characterize the way musicians grasp and hold their instruments. Callosities could be preceded by soreness and blisters of the fingertips in a harpist (harpist’s finger).1,15 Calluses were located on the lateral fourth fingertip of a drummer corresponding to the friction with the drumsticks (drummer’s digit) and on the thumb of a bassoon player. Trumpet calluses generally overlie the proximal interphalangeal joint of the left index finger.
Conclusion
Healthy nails are essential for playing a musical instrument. This review highlights the occurrence of fingertip callosities, paronychia, onycholysis, and subungual hemorrhages among musicians who play instruments. Additionally, the transmission of string-vibratory movements can produce microvascular damage and occupational Raynaud phenomenon in some musicians. These occupational nail disorders are underrecognized and may be underdiagnosed. Thus, musicians and clinicians must be aware of these alterations to adopt preventive measures and to provide adequate treatment.
- Rimmer S, Spielvogel RL. Dermatologic problems of musicians. J Am Acad Dermatol. 1990;22:657-663.
- Adams RM. Skin conditions of musicians. Cutis. 2000;65:37-38.
- Vine K, DeLeo V. Dermatologic manifestations of musicians: a case report and review of skin conditions in musicians. Cutis. 2011;87:117-121.
- Patruno C, Napolitano M, La Bella S, et al. Instrument-related skin disorders in musicians. Dermatitis. 2016;27:26-29.
- Baccouche D, Mokni M, Ben Abdelaziz A, et al. Dermatological problems of musicians: a prospective study in musical students . Article in French. Ann Dermatol Venereol. 2007;134(5 Pt 1):445-449.
- Piraccini BM, Antonucci A, Iorizzo M, et al. Occupational nail fragility in a professional violist. Contact Dermatitis. 2004;51:35-36.
- Wu JJ. Habit tic deformity secondary to guitar playing. Dermatol Online J. 2009;15:16.
- Kluger N. Piano glissando purpura: another cutaneous curiosity in musicians. J Eur Acad Dermatol Venereol. 2016;30:683.
- Alcántara-Nicolás FA, Pastor-Nieto MA, Sánchez-Herreros C, et al. Allergic contact dermatitis from acrylic nails in a flamenco guitarist. Occup Med (Lond). 2016;66:751-753.
- Baran R, Tosti A. Occupational acroosteolysis in a guitar player. Acta Derm Venereol. 1993;73:64-65.
- Destouet JM, Murphy WA. Guitar player acro-osteolysis. Skeletal Radiol. 1981;6:275-277.
- Jepsen JR, Simonsen JA. Raynaud’s phenomenon in a slap bass player: a case report. Med Probl Perform Art. 2016;31:51-53.
- Sirufo MM, Catalogna A, De Pietro F, et al. Raynaud’s phenomenon in a drummer player: microvascular disorder and nailfold video capillaroscopic findings. EXCLI J. 2021;20:1526-1531.
- Sirufo MM, Ginaldi L, De Martinis M. Raynaud’s phenomenon and the nailfold capillaroscopic findings in a guitar player. QJM. 2019;112:531-533.
- Cohen PR. Harpist’s finger: case report of a trauma-induced blister in a beginner harpist and review of string instrument-associated skin problems in musicians. Cutis. 2008;82:329-334.
- De Vasconcelos P, Soares-Almeida L, Filipe P. Subungual keratoacanthoma in a pianist. G Ital Dermatol Venereol. 2016;151:455-456.
- Young RS, Bryk D, Ratner H. Selective phalangeal tuft fractures in a guitar player. Br J Radiol. 1977;50:147-148.
- Vázquez-Osorio I, Espasandín-Arias M, García-Gavín J, et al. Allergic contact dermatitis due to acrylates in acrylic gel nails: a report of 3 cases. Actas Dermosifiliogr. 2014;105:430-432.
- Atashpaz S, Ghabili K. Color triad in guitarist’s fingers: a probable case of Raynaud’s phenomenon due to string vibration phenomenon. Med Probl Perform Art. 2008;23:143.
A variety of skin problems can occur in musicians due to the repetitive movements of playing instruments.1,2 Musicians’ nails are continuously exposed to the mechanical forces and chemical substances characteristic of their instruments.3 Occupational nail alterations in musicians caused by repetitive physical trauma, allergic contact dermatitis, and/or infection may lead to disability and compromise their professional career.
We conducted a systematic review of the literature on the clinical features of musical instrument–related nail alterations to optimize the management and prevention of these conditions.
Methods
We conducted a systematic review of PubMed, Scopus, and Google Scholar databases for eligible publications on instrument-related nail alterations in musicians using the search terms musicians with nail, onychopathy, and Raynaud. No time or language criteria were applied. Reviews, editorials, and articles not related to the topic were excluded. Bibliographies/reference lists were checked to find any additional relevant publications. Relevant articles in English and French were screened by 2 independent reviewers (A.G. and N.L.), and the following data were extracted for qualitative synthesis: sex, age, musical instrument, clinical features, number of years practicing the instrument, laboratory investigations, and disease course.
Results
The literature search yielded 11 publications. Sixteen additional articles were identified by other methods (ie, references, related publications). Overall, 3 full-text articles described general nail alterations but did not describe the clinical data, and 11 publications were editorials, commentaries, reviews, or not relevant. Thirteen contributions fulfilled the inclusion criteria and were eligible for qualitative synthesis. The flow diagram illustrates the screening process (Figure 1).
Twenty-three patients were included. The instruments identified were divided into 2 groups: string instruments (ie, guitar, violin, harp) and percussion instruments (ie, drums, piano, slap bass). Nail alterations were clinically expressed as: (1) modifications of the nail surface; (2) nail bed, soft-tissue, and bone abnormalities; and (3) periungual tissue and distal pulp disorders. All cases are summarized in the Table.4-16 Three articles described occupational Raynaud phenomenon.12-14
Comment
Modifications of the Nail Surface—Onychodystrophy, such as deformity or discoloration of the nail plate, was described in 6 patients among a cohort of 295 musicians and an additional 6 patients among 199 musicians with induced skin lesions. This condition was most common in string instrument players and pianists due to injury and irritation.
One patient, who had been a professional violist for 27 years, presented with lamellar onychoschizia, which corresponds to a horizontal splitting of the nail toward its distal portion (Figure 2). The 3 fingernails of the dominant hand were involved with a V-shaped incision of the distal margin of the nail due to the repetitive friction of the nails with the strings.6
Striations of the nail plate were reported in a guitarist who played for 10 years.7 Physical examination revealed linear transverse ridges alternating with depressions on the central aspect of the nail plate of the right thumbnail, as the patient was right-handed. This condition, attributed to sustained pressure on the string applied by the thumb, also has been called habit tic deformity.7
Nail Bed, Soft-Tissue, and Bone Lesions—Purpura (or hemorrhage) of the nail bed was associated with a percussion instrument (ie, piano) in 1 patient, affecting the second, third, and fourth fingernails of the right hand.8 Especially when performing ascending glissando passages, the pianist applies pressure that may damage the finger and cause fingernail purpura. This condition improved after the patient stopping practicing glissandi.8
Three patients—2 guitarists and 1 violist—had onycholysis, defined by a loss of the attachment between the nail bed and the nail plate (Figure 3). It may result from repetitive trauma when strings are plucked.6,9,10
Acro-osteolysis associated with pain was reported in 2 guitarists.10,11 This condition is defined as transverse lytic bands in the distal phalanges (Figure 4). Acro-osteolysis may be secondary to multiple causes, such as vinyl chloride exposure, connective tissue diseases, thermal injuries, neuropathic diseases, hyperparathyroidism, nutritional deficiencies, psoriasis, and biomechanical stress.10 In musicians playing instruments, the mechanical stress to the guitar-playing fingers is the causative factor.17
Periungual Tissue and Distal Pulp Disorders—Paronychia is an important occupational hazard of harpists, violists, and pianists.2 It represents an inflammatory condition involving the folds of tissue surrounding fingernails. Pizzicato paronychia is related to infection in the nail fold in string players and secondary to pizzicato playing, whereby the musician plucks the instrument strings with the nails and fingertips.3
Acrylates in artificial nails frequently are used among guitarists to strengthen their nails. A case of occupational allergic contact dermatitis induced by acrylic gel nails in a flamenco guitarist was described.9 The patient developed dystrophy, onycholysis, and paronychia involving the nails of the right hand where acrylic materials were used, which resolved following the removal of the artificial nails. Patch tests were performed and were positive for 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, ethylene glycol dimethacrylate, and 2-hydroxypropyl methacrylate, supporting the diagnosis of allergic contact dermatitis to acrylates.9 Therefore, musicians should be aware of the sensitizing potential of acrylates and adopt preventive measures.
Unilateral Raynaud phenomenon of the dominant hand was noted in 3 cases of musicians who played string instruments due to the increased tendency to vasospasm in the digital capillaries from the direct transmission of vibrations of the strings (>100 Hz).12-14 Consequently, the disruption of the digital blood circulation leads to an abnormal reaction to cold, which is called vibration-induced white fingers or vasospastic white finger disease.19 In these 3 patients, capillaroscopy showed a nonspecific pattern with a lack of morphologic homogeneity of capillaries, the presence of enlarged capillaries, ectasia of the efferent tract of the loops, tortuous capillaries, local hemorrhages, and neoangiogenesis.13,14
A middle-aged professional concert pianist presented with paronychia with hyperkeratosis of the lateral nail fold. Histopathology revealed a subungual keratoacanthoma eroding the distal phalanx tip, which was removed by surgical excision. The repeated fingertip trauma associated with pianistic activity was suspected to be the causative event.16
Callosities also are common on the fingertips of musicians, including 18.4% of patients in a cohort of 628 musicians, and involving fingers in 64.6% of these patients.4 These callosities are explained by the chronic mechanical forces and characterize the way musicians grasp and hold their instruments. Callosities could be preceded by soreness and blisters of the fingertips in a harpist (harpist’s finger).1,15 Calluses were located on the lateral fourth fingertip of a drummer corresponding to the friction with the drumsticks (drummer’s digit) and on the thumb of a bassoon player. Trumpet calluses generally overlie the proximal interphalangeal joint of the left index finger.
Conclusion
Healthy nails are essential for playing a musical instrument. This review highlights the occurrence of fingertip callosities, paronychia, onycholysis, and subungual hemorrhages among musicians who play instruments. Additionally, the transmission of string-vibratory movements can produce microvascular damage and occupational Raynaud phenomenon in some musicians. These occupational nail disorders are underrecognized and may be underdiagnosed. Thus, musicians and clinicians must be aware of these alterations to adopt preventive measures and to provide adequate treatment.
A variety of skin problems can occur in musicians due to the repetitive movements of playing instruments.1,2 Musicians’ nails are continuously exposed to the mechanical forces and chemical substances characteristic of their instruments.3 Occupational nail alterations in musicians caused by repetitive physical trauma, allergic contact dermatitis, and/or infection may lead to disability and compromise their professional career.
We conducted a systematic review of the literature on the clinical features of musical instrument–related nail alterations to optimize the management and prevention of these conditions.
Methods
We conducted a systematic review of PubMed, Scopus, and Google Scholar databases for eligible publications on instrument-related nail alterations in musicians using the search terms musicians with nail, onychopathy, and Raynaud. No time or language criteria were applied. Reviews, editorials, and articles not related to the topic were excluded. Bibliographies/reference lists were checked to find any additional relevant publications. Relevant articles in English and French were screened by 2 independent reviewers (A.G. and N.L.), and the following data were extracted for qualitative synthesis: sex, age, musical instrument, clinical features, number of years practicing the instrument, laboratory investigations, and disease course.
Results
The literature search yielded 11 publications. Sixteen additional articles were identified by other methods (ie, references, related publications). Overall, 3 full-text articles described general nail alterations but did not describe the clinical data, and 11 publications were editorials, commentaries, reviews, or not relevant. Thirteen contributions fulfilled the inclusion criteria and were eligible for qualitative synthesis. The flow diagram illustrates the screening process (Figure 1).
Twenty-three patients were included. The instruments identified were divided into 2 groups: string instruments (ie, guitar, violin, harp) and percussion instruments (ie, drums, piano, slap bass). Nail alterations were clinically expressed as: (1) modifications of the nail surface; (2) nail bed, soft-tissue, and bone abnormalities; and (3) periungual tissue and distal pulp disorders. All cases are summarized in the Table.4-16 Three articles described occupational Raynaud phenomenon.12-14
Comment
Modifications of the Nail Surface—Onychodystrophy, such as deformity or discoloration of the nail plate, was described in 6 patients among a cohort of 295 musicians and an additional 6 patients among 199 musicians with induced skin lesions. This condition was most common in string instrument players and pianists due to injury and irritation.
One patient, who had been a professional violist for 27 years, presented with lamellar onychoschizia, which corresponds to a horizontal splitting of the nail toward its distal portion (Figure 2). The 3 fingernails of the dominant hand were involved with a V-shaped incision of the distal margin of the nail due to the repetitive friction of the nails with the strings.6
Striations of the nail plate were reported in a guitarist who played for 10 years.7 Physical examination revealed linear transverse ridges alternating with depressions on the central aspect of the nail plate of the right thumbnail, as the patient was right-handed. This condition, attributed to sustained pressure on the string applied by the thumb, also has been called habit tic deformity.7
Nail Bed, Soft-Tissue, and Bone Lesions—Purpura (or hemorrhage) of the nail bed was associated with a percussion instrument (ie, piano) in 1 patient, affecting the second, third, and fourth fingernails of the right hand.8 Especially when performing ascending glissando passages, the pianist applies pressure that may damage the finger and cause fingernail purpura. This condition improved after the patient stopping practicing glissandi.8
Three patients—2 guitarists and 1 violist—had onycholysis, defined by a loss of the attachment between the nail bed and the nail plate (Figure 3). It may result from repetitive trauma when strings are plucked.6,9,10
Acro-osteolysis associated with pain was reported in 2 guitarists.10,11 This condition is defined as transverse lytic bands in the distal phalanges (Figure 4). Acro-osteolysis may be secondary to multiple causes, such as vinyl chloride exposure, connective tissue diseases, thermal injuries, neuropathic diseases, hyperparathyroidism, nutritional deficiencies, psoriasis, and biomechanical stress.10 In musicians playing instruments, the mechanical stress to the guitar-playing fingers is the causative factor.17
Periungual Tissue and Distal Pulp Disorders—Paronychia is an important occupational hazard of harpists, violists, and pianists.2 It represents an inflammatory condition involving the folds of tissue surrounding fingernails. Pizzicato paronychia is related to infection in the nail fold in string players and secondary to pizzicato playing, whereby the musician plucks the instrument strings with the nails and fingertips.3
Acrylates in artificial nails frequently are used among guitarists to strengthen their nails. A case of occupational allergic contact dermatitis induced by acrylic gel nails in a flamenco guitarist was described.9 The patient developed dystrophy, onycholysis, and paronychia involving the nails of the right hand where acrylic materials were used, which resolved following the removal of the artificial nails. Patch tests were performed and were positive for 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, ethylene glycol dimethacrylate, and 2-hydroxypropyl methacrylate, supporting the diagnosis of allergic contact dermatitis to acrylates.9 Therefore, musicians should be aware of the sensitizing potential of acrylates and adopt preventive measures.
Unilateral Raynaud phenomenon of the dominant hand was noted in 3 cases of musicians who played string instruments due to the increased tendency to vasospasm in the digital capillaries from the direct transmission of vibrations of the strings (>100 Hz).12-14 Consequently, the disruption of the digital blood circulation leads to an abnormal reaction to cold, which is called vibration-induced white fingers or vasospastic white finger disease.19 In these 3 patients, capillaroscopy showed a nonspecific pattern with a lack of morphologic homogeneity of capillaries, the presence of enlarged capillaries, ectasia of the efferent tract of the loops, tortuous capillaries, local hemorrhages, and neoangiogenesis.13,14
A middle-aged professional concert pianist presented with paronychia with hyperkeratosis of the lateral nail fold. Histopathology revealed a subungual keratoacanthoma eroding the distal phalanx tip, which was removed by surgical excision. The repeated fingertip trauma associated with pianistic activity was suspected to be the causative event.16
Callosities also are common on the fingertips of musicians, including 18.4% of patients in a cohort of 628 musicians, and involving fingers in 64.6% of these patients.4 These callosities are explained by the chronic mechanical forces and characterize the way musicians grasp and hold their instruments. Callosities could be preceded by soreness and blisters of the fingertips in a harpist (harpist’s finger).1,15 Calluses were located on the lateral fourth fingertip of a drummer corresponding to the friction with the drumsticks (drummer’s digit) and on the thumb of a bassoon player. Trumpet calluses generally overlie the proximal interphalangeal joint of the left index finger.
Conclusion
Healthy nails are essential for playing a musical instrument. This review highlights the occurrence of fingertip callosities, paronychia, onycholysis, and subungual hemorrhages among musicians who play instruments. Additionally, the transmission of string-vibratory movements can produce microvascular damage and occupational Raynaud phenomenon in some musicians. These occupational nail disorders are underrecognized and may be underdiagnosed. Thus, musicians and clinicians must be aware of these alterations to adopt preventive measures and to provide adequate treatment.
- Rimmer S, Spielvogel RL. Dermatologic problems of musicians. J Am Acad Dermatol. 1990;22:657-663.
- Adams RM. Skin conditions of musicians. Cutis. 2000;65:37-38.
- Vine K, DeLeo V. Dermatologic manifestations of musicians: a case report and review of skin conditions in musicians. Cutis. 2011;87:117-121.
- Patruno C, Napolitano M, La Bella S, et al. Instrument-related skin disorders in musicians. Dermatitis. 2016;27:26-29.
- Baccouche D, Mokni M, Ben Abdelaziz A, et al. Dermatological problems of musicians: a prospective study in musical students . Article in French. Ann Dermatol Venereol. 2007;134(5 Pt 1):445-449.
- Piraccini BM, Antonucci A, Iorizzo M, et al. Occupational nail fragility in a professional violist. Contact Dermatitis. 2004;51:35-36.
- Wu JJ. Habit tic deformity secondary to guitar playing. Dermatol Online J. 2009;15:16.
- Kluger N. Piano glissando purpura: another cutaneous curiosity in musicians. J Eur Acad Dermatol Venereol. 2016;30:683.
- Alcántara-Nicolás FA, Pastor-Nieto MA, Sánchez-Herreros C, et al. Allergic contact dermatitis from acrylic nails in a flamenco guitarist. Occup Med (Lond). 2016;66:751-753.
- Baran R, Tosti A. Occupational acroosteolysis in a guitar player. Acta Derm Venereol. 1993;73:64-65.
- Destouet JM, Murphy WA. Guitar player acro-osteolysis. Skeletal Radiol. 1981;6:275-277.
- Jepsen JR, Simonsen JA. Raynaud’s phenomenon in a slap bass player: a case report. Med Probl Perform Art. 2016;31:51-53.
- Sirufo MM, Catalogna A, De Pietro F, et al. Raynaud’s phenomenon in a drummer player: microvascular disorder and nailfold video capillaroscopic findings. EXCLI J. 2021;20:1526-1531.
- Sirufo MM, Ginaldi L, De Martinis M. Raynaud’s phenomenon and the nailfold capillaroscopic findings in a guitar player. QJM. 2019;112:531-533.
- Cohen PR. Harpist’s finger: case report of a trauma-induced blister in a beginner harpist and review of string instrument-associated skin problems in musicians. Cutis. 2008;82:329-334.
- De Vasconcelos P, Soares-Almeida L, Filipe P. Subungual keratoacanthoma in a pianist. G Ital Dermatol Venereol. 2016;151:455-456.
- Young RS, Bryk D, Ratner H. Selective phalangeal tuft fractures in a guitar player. Br J Radiol. 1977;50:147-148.
- Vázquez-Osorio I, Espasandín-Arias M, García-Gavín J, et al. Allergic contact dermatitis due to acrylates in acrylic gel nails: a report of 3 cases. Actas Dermosifiliogr. 2014;105:430-432.
- Atashpaz S, Ghabili K. Color triad in guitarist’s fingers: a probable case of Raynaud’s phenomenon due to string vibration phenomenon. Med Probl Perform Art. 2008;23:143.
- Rimmer S, Spielvogel RL. Dermatologic problems of musicians. J Am Acad Dermatol. 1990;22:657-663.
- Adams RM. Skin conditions of musicians. Cutis. 2000;65:37-38.
- Vine K, DeLeo V. Dermatologic manifestations of musicians: a case report and review of skin conditions in musicians. Cutis. 2011;87:117-121.
- Patruno C, Napolitano M, La Bella S, et al. Instrument-related skin disorders in musicians. Dermatitis. 2016;27:26-29.
- Baccouche D, Mokni M, Ben Abdelaziz A, et al. Dermatological problems of musicians: a prospective study in musical students . Article in French. Ann Dermatol Venereol. 2007;134(5 Pt 1):445-449.
- Piraccini BM, Antonucci A, Iorizzo M, et al. Occupational nail fragility in a professional violist. Contact Dermatitis. 2004;51:35-36.
- Wu JJ. Habit tic deformity secondary to guitar playing. Dermatol Online J. 2009;15:16.
- Kluger N. Piano glissando purpura: another cutaneous curiosity in musicians. J Eur Acad Dermatol Venereol. 2016;30:683.
- Alcántara-Nicolás FA, Pastor-Nieto MA, Sánchez-Herreros C, et al. Allergic contact dermatitis from acrylic nails in a flamenco guitarist. Occup Med (Lond). 2016;66:751-753.
- Baran R, Tosti A. Occupational acroosteolysis in a guitar player. Acta Derm Venereol. 1993;73:64-65.
- Destouet JM, Murphy WA. Guitar player acro-osteolysis. Skeletal Radiol. 1981;6:275-277.
- Jepsen JR, Simonsen JA. Raynaud’s phenomenon in a slap bass player: a case report. Med Probl Perform Art. 2016;31:51-53.
- Sirufo MM, Catalogna A, De Pietro F, et al. Raynaud’s phenomenon in a drummer player: microvascular disorder and nailfold video capillaroscopic findings. EXCLI J. 2021;20:1526-1531.
- Sirufo MM, Ginaldi L, De Martinis M. Raynaud’s phenomenon and the nailfold capillaroscopic findings in a guitar player. QJM. 2019;112:531-533.
- Cohen PR. Harpist’s finger: case report of a trauma-induced blister in a beginner harpist and review of string instrument-associated skin problems in musicians. Cutis. 2008;82:329-334.
- De Vasconcelos P, Soares-Almeida L, Filipe P. Subungual keratoacanthoma in a pianist. G Ital Dermatol Venereol. 2016;151:455-456.
- Young RS, Bryk D, Ratner H. Selective phalangeal tuft fractures in a guitar player. Br J Radiol. 1977;50:147-148.
- Vázquez-Osorio I, Espasandín-Arias M, García-Gavín J, et al. Allergic contact dermatitis due to acrylates in acrylic gel nails: a report of 3 cases. Actas Dermosifiliogr. 2014;105:430-432.
- Atashpaz S, Ghabili K. Color triad in guitarist’s fingers: a probable case of Raynaud’s phenomenon due to string vibration phenomenon. Med Probl Perform Art. 2008;23:143.
Practice Points
- Long-term practice and performance with a musical instrument predispose musicians to several skin conditions and nail disorders.
- Nail alterations in musicians include onychodystrophy, callosities of the fingertips, paronychia, distal onycholysis, lamellar onychoschizia, striations, subungual hemorrhage, and occupational Raynaud phenomenon.
- Nail lesions in musicians may be caused by localized pressure, friction-induced mechanical forces, allergic or irritant contact dermatitis, or infections.
Act Fast With Traction Alopecia to Avoid Permanent Hair Loss
The Comparison
Traction alopecia (TA) is a common type of alopecia that ultimately can result in permanent hair loss. It often is caused or worsened by repetitive and prolonged hairstyling practices such as tight ponytails, braids, or locs, or use of wigs or weaves.1 Use of headwear, as in certain religious or ethnic groups, also can be contributory.2 Individuals participating in or training for occupations involving military service or ballet are at risk for TA due to hairstyling-specific policies. Early stages of TA are reversible with proper treatment and avoidance of exacerbating factors, emphasizing the importance of prompt recognition.3
Epidemiology
Data on the true prevalence of TA are lacking. It can occur in individuals of any race or any hair type. However, it is most common in women of African descent, affecting approximately one-third of this population.4 Other commonly affected groups include ballerinas and active-duty service members due to tight ponytails and buns, as well as the Sikh population due to the use of turbans as a part of their religious practice.2,5,6
Traction alopecia also impacts children, particularly those of African descent. A 2007 study of schoolchildren in South Africa determined that more than 17% of young African girls had evidence of TA—even some as young as 6 years of age.7
Traction alopecia can be caused or exacerbated by the use of hair clips and bobby pins that aid holding styles in place.8
Hair shaft morphology may contribute to the risk for TA, with more tightly coiled hair types being more susceptible.8 Variables such as use of chemical relaxers also increase the risk for disease, especially when combined with high-tension styling methods such as braids.9
Key clinical features
Patients with TA clinically present with hair loss and breakage in areas with tension, most commonly the marginal areas of the scalp as well as the frontal hairline and temporal scalp. Hair loss can result in a “fringe sign,” in which a patient may have preservation of a thin line of hairs at the frontal aspect of the hairline with a band of hair loss behind.10 This presentation may be used to differentiate TA from other forms of alopecia, including frontal fibrosing alopecia and female pattern hair loss. When the hair loss is not marginal, it may mimic other forms of patchy hair loss including alopecia areata and trichotillomania. Other clinical findings in TA may include broken hairs, pustules, and follicular papules.10 Patients also may describe symptoms such as scalp tenderness with specific hairstyles or headaches,11 or they may be completely asymptomatic.
Trichoscopy can be helpful in guiding diagnosis and treatment. Patients with TA often have perifollicular erythema and hair casts (cylindrical structures that encircle the proximal hair shafts) in the earlier stages of the disease, with eventual loss of follicular ostia in the later stages.10,12 Hair casts also may indicate ongoing traction.12 The flambeau sign—white tracks seen on trichoscopy in the direction the hair is pulled—resembles a lit torch.13
Worth noting
Early-stage TA can be reversed by avoiding hair tension. However, patients may not be amenable to this due to personal hairstyling preferences, job duties, or religious practices. Treatment with topical or intralesional steroids or even oral antibiotics such as doxycycline for its anti-inflammatory ability may result in regrowth of lost hair if the follicles are not permanently lost and exacerbating factors are avoided.3,14 Both topical and oral minoxidil have been used with success, with minoxidil thought to increase hair density by extending the anagen (growth) phase of hair follicles.3,15 Culturally sensitive patient counseling on the condition and potential exacerbating factors is critical.16
At later stages of the disease—after loss of follicular ostia has occurred—surgical interventions should be considered,17 such as hair transplantation, which can be successful but remains a technical challenge due to variability in hair shaft curvature.18 Additionally, the cost of the procedure can limit use, and some patients may not be optimal candidates due to the extent of their hair loss. Traction alopecia may not be the only hair loss condition present. Examining the scalp is important even if the chief area of concern is the marginal scalp.
Health disparity highlight
Prevention, early identification, and treatment initiated in a timely fashion are crucial to prevent permanent hair loss. There are added societal and cultural pressures that impact hairstyle and hair care practices, especially for those with tightly coiled hair.19 Historically, tightly coiled hair has been unfairly viewed as “unprofessional,” “unkempt,” and a challenge to “manage” by some. Thus, heat, chemical relaxers, and tight hairstyles holding hair in one position have been used to straighten the hair permanently or temporarily or to keep it maintained in a style that did not necessitate excessive manipulation—often contributing to further tension on the hair.
Military service branches have evaluated and changed some hair-related policies to reflect the diverse hair types of military personnel.20 The CROWN Act (www.thecrownact.com/about)—“Creating a Respectful and Open World for Natural Hair”—is a model law passed by 26 states that prohibits race-based hair discrimination, which is the denial of employment and educational opportunities because of hair texture. Although the law has not been passed in every state, it may help individuals with tightly coiled hair to embrace natural hairstyles. However, even hairstyles with one’s own natural curl pattern can contribute to tension and thus potential development of TA.
- Larrondo J, McMichael AJ. Traction alopecia. JAMA Dermatol. 2023;159:676. doi:10.1001/jamadermatol.2022.6298
- James J, Saladi RN, Fox JL. Traction alopecia in Sikh male patients. J Am Board Fam Med. 2007;20:497-498. doi:10.3122/jabfm.2007.05.070076
- Callender VD, McMichael AJ, Cohen GF. Medical and surgical therapies for alopecias in black women. Dermatol Ther. 2004;17:164-176.
- Loussouarn G, El Rawadi C, Genain G. Diversity of hair growth profiles. Int J Dermatol. 2005;44(suppl 1):6-9.
- Samrao AChen CZedek Det al. Traction alopecia in a ballerina: clinicopathologic features. Arch Dermatol. 2010;146:918-935. doi:10.1001/archdermatol.2010.183
- Korona-Bailey J, Banaag A, Nguyen DR, et al. Free the bun: prevalence of alopecia among active duty service women, fiscal years 2010-2019. Mil Med. 2023;188:e492-e496. doi:10.1093/milmed/usab274
- Khumalo NP, Jessop S, Gumedze F, et al. Hairdressing is associated with scalp disease in African schoolchildren. Br J Dermatol. 2007;157:106-110. doi:10.1111/j.1365-2133.2007.07987.x
- Billero V, Miteva M. Traction alopecia: the root of the problem. Clin Cosmet Investig Dermatol. 2018;11:149-159. doi:10.2147/CCID.S137296
- Haskin A, Aguh C. All hairstyles are not created equal: what the dermatologist needs to know about black hairstyling practices and the risk of traction alopecia (TA). J Am Acad Dermatol. 2016;75:606-611. doi:10.1016/j.jaad.2016.02.1162
- Samrao A, Price VH, Zedek D, et al. The “fringe sign”—a useful clinical finding in traction alopecia of the marginal hair line. Dermatol Online J. 2011;17:1.
- Kararizou E, Bougea AM, Giotopoulou D, et al. An update on the less-known group of other primary headaches—a review. Eur Neurol Rev. 2014;9:71-77. doi:10.17925/ENR.2014.09.01.71
- Tosti A, Miteva M, Torres F, et al. Hair casts are a dermoscopic clue for the diagnosis of traction alopecia. Br J Dermatol. 2010;163:1353-1355.
- Agrawal S, Daruwalla SB, Dhurat RS. The flambeau sign—a new dermoscopy finding in a case of marginal traction alopecia. Australas J Dermatol. 2020;61:49-50. doi:10. 1111/ajd.13187
- Lawson CN, Hollinger J, Sethi S, et al. Updates in the understanding and treatments of skin & hair disorders in women of color. Int J Womens Dermatol. 2017;3:S21-S37.
- Awad A, Chim I, Sharma P, et al. Low-dose oral minoxidil improves hair density in traction alopecia. J Am Acad Dermatol. 2023;89:157-159. doi:10.1016/j.jaad.2023.02.024
- Grayson C, Heath CR. Counseling about traction alopecia: a “compliment, discuss, and suggest” method. Cutis. 2021;108:20-22.
- Ozçelik D. Extensive traction alopecia attributable to ponytail hairstyle and its treatment with hair transplantation. Aesthetic Plast Surg. 2005;29:325-327. doi:10.1007/s00266-005-0004-5
- Singh MK, Avram MR. Technical considerations for follicular unit extraction in African-American hair. Dermatol Surg. 2013;39:1282-1284. doi:10.1111/dsu.12229
- Jones NL, Heath CR. Hair at the intersection of dermatology and anthropology: a conversation on race and relationships. Pediatr Dermatol. 2021;38(suppl 2):158-160.
- Franklin JMM, Wohltmann WE, Wong EB. From buns to braids and ponytails: entering a new era of female military hair-grooming standards. Cutis. 2021;108:31-35. doi:10.12788/cutis.0296
The Comparison
Traction alopecia (TA) is a common type of alopecia that ultimately can result in permanent hair loss. It often is caused or worsened by repetitive and prolonged hairstyling practices such as tight ponytails, braids, or locs, or use of wigs or weaves.1 Use of headwear, as in certain religious or ethnic groups, also can be contributory.2 Individuals participating in or training for occupations involving military service or ballet are at risk for TA due to hairstyling-specific policies. Early stages of TA are reversible with proper treatment and avoidance of exacerbating factors, emphasizing the importance of prompt recognition.3
Epidemiology
Data on the true prevalence of TA are lacking. It can occur in individuals of any race or any hair type. However, it is most common in women of African descent, affecting approximately one-third of this population.4 Other commonly affected groups include ballerinas and active-duty service members due to tight ponytails and buns, as well as the Sikh population due to the use of turbans as a part of their religious practice.2,5,6
Traction alopecia also impacts children, particularly those of African descent. A 2007 study of schoolchildren in South Africa determined that more than 17% of young African girls had evidence of TA—even some as young as 6 years of age.7
Traction alopecia can be caused or exacerbated by the use of hair clips and bobby pins that aid holding styles in place.8
Hair shaft morphology may contribute to the risk for TA, with more tightly coiled hair types being more susceptible.8 Variables such as use of chemical relaxers also increase the risk for disease, especially when combined with high-tension styling methods such as braids.9
Key clinical features
Patients with TA clinically present with hair loss and breakage in areas with tension, most commonly the marginal areas of the scalp as well as the frontal hairline and temporal scalp. Hair loss can result in a “fringe sign,” in which a patient may have preservation of a thin line of hairs at the frontal aspect of the hairline with a band of hair loss behind.10 This presentation may be used to differentiate TA from other forms of alopecia, including frontal fibrosing alopecia and female pattern hair loss. When the hair loss is not marginal, it may mimic other forms of patchy hair loss including alopecia areata and trichotillomania. Other clinical findings in TA may include broken hairs, pustules, and follicular papules.10 Patients also may describe symptoms such as scalp tenderness with specific hairstyles or headaches,11 or they may be completely asymptomatic.
Trichoscopy can be helpful in guiding diagnosis and treatment. Patients with TA often have perifollicular erythema and hair casts (cylindrical structures that encircle the proximal hair shafts) in the earlier stages of the disease, with eventual loss of follicular ostia in the later stages.10,12 Hair casts also may indicate ongoing traction.12 The flambeau sign—white tracks seen on trichoscopy in the direction the hair is pulled—resembles a lit torch.13
Worth noting
Early-stage TA can be reversed by avoiding hair tension. However, patients may not be amenable to this due to personal hairstyling preferences, job duties, or religious practices. Treatment with topical or intralesional steroids or even oral antibiotics such as doxycycline for its anti-inflammatory ability may result in regrowth of lost hair if the follicles are not permanently lost and exacerbating factors are avoided.3,14 Both topical and oral minoxidil have been used with success, with minoxidil thought to increase hair density by extending the anagen (growth) phase of hair follicles.3,15 Culturally sensitive patient counseling on the condition and potential exacerbating factors is critical.16
At later stages of the disease—after loss of follicular ostia has occurred—surgical interventions should be considered,17 such as hair transplantation, which can be successful but remains a technical challenge due to variability in hair shaft curvature.18 Additionally, the cost of the procedure can limit use, and some patients may not be optimal candidates due to the extent of their hair loss. Traction alopecia may not be the only hair loss condition present. Examining the scalp is important even if the chief area of concern is the marginal scalp.
Health disparity highlight
Prevention, early identification, and treatment initiated in a timely fashion are crucial to prevent permanent hair loss. There are added societal and cultural pressures that impact hairstyle and hair care practices, especially for those with tightly coiled hair.19 Historically, tightly coiled hair has been unfairly viewed as “unprofessional,” “unkempt,” and a challenge to “manage” by some. Thus, heat, chemical relaxers, and tight hairstyles holding hair in one position have been used to straighten the hair permanently or temporarily or to keep it maintained in a style that did not necessitate excessive manipulation—often contributing to further tension on the hair.
Military service branches have evaluated and changed some hair-related policies to reflect the diverse hair types of military personnel.20 The CROWN Act (www.thecrownact.com/about)—“Creating a Respectful and Open World for Natural Hair”—is a model law passed by 26 states that prohibits race-based hair discrimination, which is the denial of employment and educational opportunities because of hair texture. Although the law has not been passed in every state, it may help individuals with tightly coiled hair to embrace natural hairstyles. However, even hairstyles with one’s own natural curl pattern can contribute to tension and thus potential development of TA.
The Comparison
Traction alopecia (TA) is a common type of alopecia that ultimately can result in permanent hair loss. It often is caused or worsened by repetitive and prolonged hairstyling practices such as tight ponytails, braids, or locs, or use of wigs or weaves.1 Use of headwear, as in certain religious or ethnic groups, also can be contributory.2 Individuals participating in or training for occupations involving military service or ballet are at risk for TA due to hairstyling-specific policies. Early stages of TA are reversible with proper treatment and avoidance of exacerbating factors, emphasizing the importance of prompt recognition.3
Epidemiology
Data on the true prevalence of TA are lacking. It can occur in individuals of any race or any hair type. However, it is most common in women of African descent, affecting approximately one-third of this population.4 Other commonly affected groups include ballerinas and active-duty service members due to tight ponytails and buns, as well as the Sikh population due to the use of turbans as a part of their religious practice.2,5,6
Traction alopecia also impacts children, particularly those of African descent. A 2007 study of schoolchildren in South Africa determined that more than 17% of young African girls had evidence of TA—even some as young as 6 years of age.7
Traction alopecia can be caused or exacerbated by the use of hair clips and bobby pins that aid holding styles in place.8
Hair shaft morphology may contribute to the risk for TA, with more tightly coiled hair types being more susceptible.8 Variables such as use of chemical relaxers also increase the risk for disease, especially when combined with high-tension styling methods such as braids.9
Key clinical features
Patients with TA clinically present with hair loss and breakage in areas with tension, most commonly the marginal areas of the scalp as well as the frontal hairline and temporal scalp. Hair loss can result in a “fringe sign,” in which a patient may have preservation of a thin line of hairs at the frontal aspect of the hairline with a band of hair loss behind.10 This presentation may be used to differentiate TA from other forms of alopecia, including frontal fibrosing alopecia and female pattern hair loss. When the hair loss is not marginal, it may mimic other forms of patchy hair loss including alopecia areata and trichotillomania. Other clinical findings in TA may include broken hairs, pustules, and follicular papules.10 Patients also may describe symptoms such as scalp tenderness with specific hairstyles or headaches,11 or they may be completely asymptomatic.
Trichoscopy can be helpful in guiding diagnosis and treatment. Patients with TA often have perifollicular erythema and hair casts (cylindrical structures that encircle the proximal hair shafts) in the earlier stages of the disease, with eventual loss of follicular ostia in the later stages.10,12 Hair casts also may indicate ongoing traction.12 The flambeau sign—white tracks seen on trichoscopy in the direction the hair is pulled—resembles a lit torch.13
Worth noting
Early-stage TA can be reversed by avoiding hair tension. However, patients may not be amenable to this due to personal hairstyling preferences, job duties, or religious practices. Treatment with topical or intralesional steroids or even oral antibiotics such as doxycycline for its anti-inflammatory ability may result in regrowth of lost hair if the follicles are not permanently lost and exacerbating factors are avoided.3,14 Both topical and oral minoxidil have been used with success, with minoxidil thought to increase hair density by extending the anagen (growth) phase of hair follicles.3,15 Culturally sensitive patient counseling on the condition and potential exacerbating factors is critical.16
At later stages of the disease—after loss of follicular ostia has occurred—surgical interventions should be considered,17 such as hair transplantation, which can be successful but remains a technical challenge due to variability in hair shaft curvature.18 Additionally, the cost of the procedure can limit use, and some patients may not be optimal candidates due to the extent of their hair loss. Traction alopecia may not be the only hair loss condition present. Examining the scalp is important even if the chief area of concern is the marginal scalp.
Health disparity highlight
Prevention, early identification, and treatment initiated in a timely fashion are crucial to prevent permanent hair loss. There are added societal and cultural pressures that impact hairstyle and hair care practices, especially for those with tightly coiled hair.19 Historically, tightly coiled hair has been unfairly viewed as “unprofessional,” “unkempt,” and a challenge to “manage” by some. Thus, heat, chemical relaxers, and tight hairstyles holding hair in one position have been used to straighten the hair permanently or temporarily or to keep it maintained in a style that did not necessitate excessive manipulation—often contributing to further tension on the hair.
Military service branches have evaluated and changed some hair-related policies to reflect the diverse hair types of military personnel.20 The CROWN Act (www.thecrownact.com/about)—“Creating a Respectful and Open World for Natural Hair”—is a model law passed by 26 states that prohibits race-based hair discrimination, which is the denial of employment and educational opportunities because of hair texture. Although the law has not been passed in every state, it may help individuals with tightly coiled hair to embrace natural hairstyles. However, even hairstyles with one’s own natural curl pattern can contribute to tension and thus potential development of TA.
- Larrondo J, McMichael AJ. Traction alopecia. JAMA Dermatol. 2023;159:676. doi:10.1001/jamadermatol.2022.6298
- James J, Saladi RN, Fox JL. Traction alopecia in Sikh male patients. J Am Board Fam Med. 2007;20:497-498. doi:10.3122/jabfm.2007.05.070076
- Callender VD, McMichael AJ, Cohen GF. Medical and surgical therapies for alopecias in black women. Dermatol Ther. 2004;17:164-176.
- Loussouarn G, El Rawadi C, Genain G. Diversity of hair growth profiles. Int J Dermatol. 2005;44(suppl 1):6-9.
- Samrao AChen CZedek Det al. Traction alopecia in a ballerina: clinicopathologic features. Arch Dermatol. 2010;146:918-935. doi:10.1001/archdermatol.2010.183
- Korona-Bailey J, Banaag A, Nguyen DR, et al. Free the bun: prevalence of alopecia among active duty service women, fiscal years 2010-2019. Mil Med. 2023;188:e492-e496. doi:10.1093/milmed/usab274
- Khumalo NP, Jessop S, Gumedze F, et al. Hairdressing is associated with scalp disease in African schoolchildren. Br J Dermatol. 2007;157:106-110. doi:10.1111/j.1365-2133.2007.07987.x
- Billero V, Miteva M. Traction alopecia: the root of the problem. Clin Cosmet Investig Dermatol. 2018;11:149-159. doi:10.2147/CCID.S137296
- Haskin A, Aguh C. All hairstyles are not created equal: what the dermatologist needs to know about black hairstyling practices and the risk of traction alopecia (TA). J Am Acad Dermatol. 2016;75:606-611. doi:10.1016/j.jaad.2016.02.1162
- Samrao A, Price VH, Zedek D, et al. The “fringe sign”—a useful clinical finding in traction alopecia of the marginal hair line. Dermatol Online J. 2011;17:1.
- Kararizou E, Bougea AM, Giotopoulou D, et al. An update on the less-known group of other primary headaches—a review. Eur Neurol Rev. 2014;9:71-77. doi:10.17925/ENR.2014.09.01.71
- Tosti A, Miteva M, Torres F, et al. Hair casts are a dermoscopic clue for the diagnosis of traction alopecia. Br J Dermatol. 2010;163:1353-1355.
- Agrawal S, Daruwalla SB, Dhurat RS. The flambeau sign—a new dermoscopy finding in a case of marginal traction alopecia. Australas J Dermatol. 2020;61:49-50. doi:10. 1111/ajd.13187
- Lawson CN, Hollinger J, Sethi S, et al. Updates in the understanding and treatments of skin & hair disorders in women of color. Int J Womens Dermatol. 2017;3:S21-S37.
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- Lawson CN, Hollinger J, Sethi S, et al. Updates in the understanding and treatments of skin & hair disorders in women of color. Int J Womens Dermatol. 2017;3:S21-S37.
- Awad A, Chim I, Sharma P, et al. Low-dose oral minoxidil improves hair density in traction alopecia. J Am Acad Dermatol. 2023;89:157-159. doi:10.1016/j.jaad.2023.02.024
- Grayson C, Heath CR. Counseling about traction alopecia: a “compliment, discuss, and suggest” method. Cutis. 2021;108:20-22.
- Ozçelik D. Extensive traction alopecia attributable to ponytail hairstyle and its treatment with hair transplantation. Aesthetic Plast Surg. 2005;29:325-327. doi:10.1007/s00266-005-0004-5
- Singh MK, Avram MR. Technical considerations for follicular unit extraction in African-American hair. Dermatol Surg. 2013;39:1282-1284. doi:10.1111/dsu.12229
- Jones NL, Heath CR. Hair at the intersection of dermatology and anthropology: a conversation on race and relationships. Pediatr Dermatol. 2021;38(suppl 2):158-160.
- Franklin JMM, Wohltmann WE, Wong EB. From buns to braids and ponytails: entering a new era of female military hair-grooming standards. Cutis. 2021;108:31-35. doi:10.12788/cutis.0296
