NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.

NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.

NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?

BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.

Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.

Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.

BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.

CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?

BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.

Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.

Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.

BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.

CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?

BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.

Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.

Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.

BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.

CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

Clinical Question: Does physician sex affect hospitalized patient outcomes?

Background: Previous studies had suggested different practice patterns between male and female physicians in process measure of quality. No prior evaluation of patient outcomes examining those differences was studied in the past.

Also, 30-day readmission rate, after adjustment readmissions (from 1,540,797 hospitalizations) was 15.02% vs. 15.57% (adjusted risk difference, –0.55%; 95% confidence interval, –0.71% to 0.39%; P less than .001) showing that the care provided by a female physician can reduce one readmission when treating 182 patients.

Bottom line: Patients older than 65 years have lower 30-day mortality and readmission rates when receiving inpatient care from a female internist, compared with care by a male internist.

Citations: Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs. female physicians. JAMA Intern Med. 2017 Feb;177(2):206-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Does physician sex affect hospitalized patient outcomes?

Background: Previous studies had suggested different practice patterns between male and female physicians in process measure of quality. No prior evaluation of patient outcomes examining those differences was studied in the past.

Also, 30-day readmission rate, after adjustment readmissions (from 1,540,797 hospitalizations) was 15.02% vs. 15.57% (adjusted risk difference, –0.55%; 95% confidence interval, –0.71% to 0.39%; P less than .001) showing that the care provided by a female physician can reduce one readmission when treating 182 patients.

Bottom line: Patients older than 65 years have lower 30-day mortality and readmission rates when receiving inpatient care from a female internist, compared with care by a male internist.

Citations: Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs. female physicians. JAMA Intern Med. 2017 Feb;177(2):206-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Does physician sex affect hospitalized patient outcomes?

Background: Previous studies had suggested different practice patterns between male and female physicians in process measure of quality. No prior evaluation of patient outcomes examining those differences was studied in the past.

Also, 30-day readmission rate, after adjustment readmissions (from 1,540,797 hospitalizations) was 15.02% vs. 15.57% (adjusted risk difference, –0.55%; 95% confidence interval, –0.71% to 0.39%; P less than .001) showing that the care provided by a female physician can reduce one readmission when treating 182 patients.

Bottom line: Patients older than 65 years have lower 30-day mortality and readmission rates when receiving inpatient care from a female internist, compared with care by a male internist.

Citations: Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs. female physicians. JAMA Intern Med. 2017 Feb;177(2):206-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Are hospitalized patients experiencing an increased mortality risk at the end-rotation resident transition in care and is this association related to the Accreditation Council for Graduate Medical Education (ACGME) 2011 duty-hour regulations?

Background: Prior studies of physicians’ transitions in care were associated with potential adverse patient events and outcomes. A higher mortality risk was suggested among patients with a complex hospital course or prolonged length of stay in association to house-staff transitions of care.

Bottom line: Elevated in-hospital mortality was seen among patients admitted to the inpatient medicine service at the end-of-rotation resident transitions in care. The association was stronger after the duty-hour ACGME (2011) regulations.

Citations: Denson JL, Jensen A, Saag HS, et al. Association between end-of-rotation resident transition in care and mortality among hospitalized patients. JAMA. 2016 Dec 6;316(21):2204-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Are hospitalized patients experiencing an increased mortality risk at the end-rotation resident transition in care and is this association related to the Accreditation Council for Graduate Medical Education (ACGME) 2011 duty-hour regulations?

Background: Prior studies of physicians’ transitions in care were associated with potential adverse patient events and outcomes. A higher mortality risk was suggested among patients with a complex hospital course or prolonged length of stay in association to house-staff transitions of care.

Bottom line: Elevated in-hospital mortality was seen among patients admitted to the inpatient medicine service at the end-of-rotation resident transitions in care. The association was stronger after the duty-hour ACGME (2011) regulations.

Citations: Denson JL, Jensen A, Saag HS, et al. Association between end-of-rotation resident transition in care and mortality among hospitalized patients. JAMA. 2016 Dec 6;316(21):2204-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Are hospitalized patients experiencing an increased mortality risk at the end-rotation resident transition in care and is this association related to the Accreditation Council for Graduate Medical Education (ACGME) 2011 duty-hour regulations?

Background: Prior studies of physicians’ transitions in care were associated with potential adverse patient events and outcomes. A higher mortality risk was suggested among patients with a complex hospital course or prolonged length of stay in association to house-staff transitions of care.

Bottom line: Elevated in-hospital mortality was seen among patients admitted to the inpatient medicine service at the end-of-rotation resident transitions in care. The association was stronger after the duty-hour ACGME (2011) regulations.

Citations: Denson JL, Jensen A, Saag HS, et al. Association between end-of-rotation resident transition in care and mortality among hospitalized patients. JAMA. 2016 Dec 6;316(21):2204-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

ORLANDO – The applications for picowavelength lasers are expanding, with emerging data on their uses for cosmetic indications other than tattoo removal, according to Anne Chapas, MD, who is in private practice in New York.

First introduced and cleared by the Food and Drug Administration for tattoo removal, “picowave devices ... are now being studied in multiple different cosmetic conditions, including their use in acne scars, fine lines and wrinkles, and melasma,” Dr. Chapas said in a video interview at the annual meeting of the American Academy of Dermatology.

The No. 1 thing dermatologists need to know is that these types of lasers are delivering energy extremely quickly,” at 1,000 times faster than nanosecond lasers, she said. Another difference between the two is that “the laser tissue interaction between the two types of devices is completely different.”

In the interview, she highlighted other important points about picowave lasers, including less downtime after treatment.

At the meeting, Dr. Chapas spoke during a session entitled “the Science Behind New Devices in Dermatology.”

Her disclosures include serving as a consultant and investigator for Syneron and Candela.

emechcatie@frontlinemedcom.com

ORLANDO – The applications for picowavelength lasers are expanding, with emerging data on their uses for cosmetic indications other than tattoo removal, according to Anne Chapas, MD, who is in private practice in New York.

First introduced and cleared by the Food and Drug Administration for tattoo removal, “picowave devices ... are now being studied in multiple different cosmetic conditions, including their use in acne scars, fine lines and wrinkles, and melasma,” Dr. Chapas said in a video interview at the annual meeting of the American Academy of Dermatology.

The No. 1 thing dermatologists need to know is that these types of lasers are delivering energy extremely quickly,” at 1,000 times faster than nanosecond lasers, she said. Another difference between the two is that “the laser tissue interaction between the two types of devices is completely different.”

In the interview, she highlighted other important points about picowave lasers, including less downtime after treatment.

At the meeting, Dr. Chapas spoke during a session entitled “the Science Behind New Devices in Dermatology.”

Her disclosures include serving as a consultant and investigator for Syneron and Candela.

emechcatie@frontlinemedcom.com

ORLANDO – The applications for picowavelength lasers are expanding, with emerging data on their uses for cosmetic indications other than tattoo removal, according to Anne Chapas, MD, who is in private practice in New York.

First introduced and cleared by the Food and Drug Administration for tattoo removal, “picowave devices ... are now being studied in multiple different cosmetic conditions, including their use in acne scars, fine lines and wrinkles, and melasma,” Dr. Chapas said in a video interview at the annual meeting of the American Academy of Dermatology.

The No. 1 thing dermatologists need to know is that these types of lasers are delivering energy extremely quickly,” at 1,000 times faster than nanosecond lasers, she said. Another difference between the two is that “the laser tissue interaction between the two types of devices is completely different.”

In the interview, she highlighted other important points about picowave lasers, including less downtime after treatment.

At the meeting, Dr. Chapas spoke during a session entitled “the Science Behind New Devices in Dermatology.”

Her disclosures include serving as a consultant and investigator for Syneron and Candela.

emechcatie@frontlinemedcom.com

WASHINGTON – Patients who regularly accessed 30 minute, Internet-based behavioral counseling videos cut their systolic blood pressure, compared with baseline over 1 year by an average 4 mm Hg more than control patients in a randomized, phase II study with 264 patients.

Electronic counseling (e-counseling) “enhanced the efficacy of usual care for hypertension,” Robert P. Nolan, Ph.D., said at the annual meeting of the American College of Cardiology.

“We hope to optimize the efficacy of medical treatments with a behavioral intervention,” said Dr. Nolan, who added that the magnitude of the added benefit from the e-counseling program was “like adding an additional antihypertensive medication.”

“We know antihypertensive treatments work, but compliance is a huge challenge” for health care providers, commented E. Magnus Ohman, MBBS, a professor and cardiologist at Duke University in Durham, N.C. “Having a new way to enhance compliance would be fantastic,” he said.

The Internet-based counseling program devised by Dr. Nolan and his associates consisted of a year-long series of 28 videos, each about 30 minutes long, that participants in the active arm accessed over the Internet. During the study, participants received a series of emailed messages that sent links to the videos on a set schedule over 12 months: During the first 4 months they received an emailed link weekly, during the next 4 months they received an emailed link to a new video every other week, and during the final 4 months of the intervention participants received emailed links once a month. Patients could access each video more than once if they wished, and they were free to share the links with any family members or friends who helped the patients with lifestyle management of their hypertension.

Patients in the e-counseling intervention arm received links to videos that focused on motivational messages and teaching cognitive behavioral skills. Patients in the control arm received emails with generic messages on blood pressure management and without links to videos.

The REACH (E-Counseling Promotes Blood Pressure Reduction and Therapeutic Lifestyle Change in Hypertension) study ran at four Canadian sites. It sent invitations to participate to 609 patients with stage 1 or 2 hypertension, with a blood pressure prior to treatment of 140/90-180/110 mm Hg. Among the invited patients, 264 elected to participate; 100 patients in the e-counseling arm and 97 control patients completed the 1-year program. Participants averaged 58 years of age, their average body mass index was 31 kg/m², and 9% smoked. Their blood pressure at entry averaged 141/87 mm Hg, their average pulse pressure was about 54 mm Hg, and their average 10-year risk for a cardiovascular disease event, measured by the Framingham Risk Score, was about 16%. At entry, patients in the study received an average of 1.5 antihypertensive drugs each.

At the end of the 1-year program, systolic blood pressure fell by an average of 6 mm Hg from baseline among patients who completed the control program, and by an average of 10.1 mm Hg among the patients who completed the e-counseling arm, a statistically significant difference for one of the study’s primary endpoints. Change in pulse pressure from baseline showed an average 1.5–mm Hg drop in the control patients and an average 4.3–mm Hg decline in the e-counseling patients, another statistically significant difference for a second primary endpoint, reported Dr. Nolan, a clinical psychologist and director of the cardiac eHealth program at the University of Toronto.

A third primary endpoint was change in the Framingham Risk Score, which fell by an average of 1.9% after 12 months in the e-counseling patients and rose by an average of 0.2% among the controls.

The final primary endpoint was the change in diastolic blood pressure from baseline, which showed a better than 4–mm Hg incremental decline in the men who received e-counseling, compared with controls, but among women in the study, the drop in diastolic blood pressure from baseline was nearly the same – about 6 mm Hg – in both the controls and e-counseling patients.

“This tells us that we need to better tailor the [e-counseling] intervention to men and to women,” Dr. Nolan said in a video interview. He also envisions better tailoring of the e-counseling videos to various socioeconomic and ethnic groups. He plans to continue testing of a revised version of the e-counseling intervention in a larger, phase III study, but he also hopes that the intervention videos can soon be available at no charge for use in routine practice.

REACH received no commercial funding. Dr. Nolan had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

WASHINGTON – Patients who regularly accessed 30 minute, Internet-based behavioral counseling videos cut their systolic blood pressure, compared with baseline over 1 year by an average 4 mm Hg more than control patients in a randomized, phase II study with 264 patients.

Electronic counseling (e-counseling) “enhanced the efficacy of usual care for hypertension,” Robert P. Nolan, Ph.D., said at the annual meeting of the American College of Cardiology.

“We hope to optimize the efficacy of medical treatments with a behavioral intervention,” said Dr. Nolan, who added that the magnitude of the added benefit from the e-counseling program was “like adding an additional antihypertensive medication.”

“We know antihypertensive treatments work, but compliance is a huge challenge” for health care providers, commented E. Magnus Ohman, MBBS, a professor and cardiologist at Duke University in Durham, N.C. “Having a new way to enhance compliance would be fantastic,” he said.

The Internet-based counseling program devised by Dr. Nolan and his associates consisted of a year-long series of 28 videos, each about 30 minutes long, that participants in the active arm accessed over the Internet. During the study, participants received a series of emailed messages that sent links to the videos on a set schedule over 12 months: During the first 4 months they received an emailed link weekly, during the next 4 months they received an emailed link to a new video every other week, and during the final 4 months of the intervention participants received emailed links once a month. Patients could access each video more than once if they wished, and they were free to share the links with any family members or friends who helped the patients with lifestyle management of their hypertension.

Patients in the e-counseling intervention arm received links to videos that focused on motivational messages and teaching cognitive behavioral skills. Patients in the control arm received emails with generic messages on blood pressure management and without links to videos.

The REACH (E-Counseling Promotes Blood Pressure Reduction and Therapeutic Lifestyle Change in Hypertension) study ran at four Canadian sites. It sent invitations to participate to 609 patients with stage 1 or 2 hypertension, with a blood pressure prior to treatment of 140/90-180/110 mm Hg. Among the invited patients, 264 elected to participate; 100 patients in the e-counseling arm and 97 control patients completed the 1-year program. Participants averaged 58 years of age, their average body mass index was 31 kg/m², and 9% smoked. Their blood pressure at entry averaged 141/87 mm Hg, their average pulse pressure was about 54 mm Hg, and their average 10-year risk for a cardiovascular disease event, measured by the Framingham Risk Score, was about 16%. At entry, patients in the study received an average of 1.5 antihypertensive drugs each.

At the end of the 1-year program, systolic blood pressure fell by an average of 6 mm Hg from baseline among patients who completed the control program, and by an average of 10.1 mm Hg among the patients who completed the e-counseling arm, a statistically significant difference for one of the study’s primary endpoints. Change in pulse pressure from baseline showed an average 1.5–mm Hg drop in the control patients and an average 4.3–mm Hg decline in the e-counseling patients, another statistically significant difference for a second primary endpoint, reported Dr. Nolan, a clinical psychologist and director of the cardiac eHealth program at the University of Toronto.

A third primary endpoint was change in the Framingham Risk Score, which fell by an average of 1.9% after 12 months in the e-counseling patients and rose by an average of 0.2% among the controls.

The final primary endpoint was the change in diastolic blood pressure from baseline, which showed a better than 4–mm Hg incremental decline in the men who received e-counseling, compared with controls, but among women in the study, the drop in diastolic blood pressure from baseline was nearly the same – about 6 mm Hg – in both the controls and e-counseling patients.

“This tells us that we need to better tailor the [e-counseling] intervention to men and to women,” Dr. Nolan said in a video interview. He also envisions better tailoring of the e-counseling videos to various socioeconomic and ethnic groups. He plans to continue testing of a revised version of the e-counseling intervention in a larger, phase III study, but he also hopes that the intervention videos can soon be available at no charge for use in routine practice.

REACH received no commercial funding. Dr. Nolan had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

WASHINGTON – Patients who regularly accessed 30 minute, Internet-based behavioral counseling videos cut their systolic blood pressure, compared with baseline over 1 year by an average 4 mm Hg more than control patients in a randomized, phase II study with 264 patients.

Electronic counseling (e-counseling) “enhanced the efficacy of usual care for hypertension,” Robert P. Nolan, Ph.D., said at the annual meeting of the American College of Cardiology.

“We hope to optimize the efficacy of medical treatments with a behavioral intervention,” said Dr. Nolan, who added that the magnitude of the added benefit from the e-counseling program was “like adding an additional antihypertensive medication.”

“We know antihypertensive treatments work, but compliance is a huge challenge” for health care providers, commented E. Magnus Ohman, MBBS, a professor and cardiologist at Duke University in Durham, N.C. “Having a new way to enhance compliance would be fantastic,” he said.

The Internet-based counseling program devised by Dr. Nolan and his associates consisted of a year-long series of 28 videos, each about 30 minutes long, that participants in the active arm accessed over the Internet. During the study, participants received a series of emailed messages that sent links to the videos on a set schedule over 12 months: During the first 4 months they received an emailed link weekly, during the next 4 months they received an emailed link to a new video every other week, and during the final 4 months of the intervention participants received emailed links once a month. Patients could access each video more than once if they wished, and they were free to share the links with any family members or friends who helped the patients with lifestyle management of their hypertension.

Patients in the e-counseling intervention arm received links to videos that focused on motivational messages and teaching cognitive behavioral skills. Patients in the control arm received emails with generic messages on blood pressure management and without links to videos.

The REACH (E-Counseling Promotes Blood Pressure Reduction and Therapeutic Lifestyle Change in Hypertension) study ran at four Canadian sites. It sent invitations to participate to 609 patients with stage 1 or 2 hypertension, with a blood pressure prior to treatment of 140/90-180/110 mm Hg. Among the invited patients, 264 elected to participate; 100 patients in the e-counseling arm and 97 control patients completed the 1-year program. Participants averaged 58 years of age, their average body mass index was 31 kg/m², and 9% smoked. Their blood pressure at entry averaged 141/87 mm Hg, their average pulse pressure was about 54 mm Hg, and their average 10-year risk for a cardiovascular disease event, measured by the Framingham Risk Score, was about 16%. At entry, patients in the study received an average of 1.5 antihypertensive drugs each.

At the end of the 1-year program, systolic blood pressure fell by an average of 6 mm Hg from baseline among patients who completed the control program, and by an average of 10.1 mm Hg among the patients who completed the e-counseling arm, a statistically significant difference for one of the study’s primary endpoints. Change in pulse pressure from baseline showed an average 1.5–mm Hg drop in the control patients and an average 4.3–mm Hg decline in the e-counseling patients, another statistically significant difference for a second primary endpoint, reported Dr. Nolan, a clinical psychologist and director of the cardiac eHealth program at the University of Toronto.

A third primary endpoint was change in the Framingham Risk Score, which fell by an average of 1.9% after 12 months in the e-counseling patients and rose by an average of 0.2% among the controls.

The final primary endpoint was the change in diastolic blood pressure from baseline, which showed a better than 4–mm Hg incremental decline in the men who received e-counseling, compared with controls, but among women in the study, the drop in diastolic blood pressure from baseline was nearly the same – about 6 mm Hg – in both the controls and e-counseling patients.

“This tells us that we need to better tailor the [e-counseling] intervention to men and to women,” Dr. Nolan said in a video interview. He also envisions better tailoring of the e-counseling videos to various socioeconomic and ethnic groups. He plans to continue testing of a revised version of the e-counseling intervention in a larger, phase III study, but he also hopes that the intervention videos can soon be available at no charge for use in routine practice.

REACH received no commercial funding. Dr. Nolan had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ORLANDO – It may be time to start considering new options for treating keloids, according to Amy McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C.

At the annual meeting of the American Academy of Dermatology, Dr. McMichael discussed one of the highlights of the annual symposium of the Skin of Color Society, held right before the annual meeting, a presentation by Michael Tirgan, MD, who has treated patients with keloids for about 10 years.

Dr. Tirgan, an oncologist based in New York, has a large database and registry of patients and shared some interesting data at the symposium. “What he’s found is that those who come with the supermassive and massive keloids are those who have had the most surgery on their keloid,” Dr. McMichael said in a video interview at the meeting.

His findings shed light on what she described as “a new perspective in the way that we think about keloids” and a new approach to treatment – considering keloids as tumors – not just a scar.

Dr. McMichael had no relevant disclosures.

emechcatie@frontlinemedcom.com

ORLANDO – It may be time to start considering new options for treating keloids, according to Amy McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C.

At the annual meeting of the American Academy of Dermatology, Dr. McMichael discussed one of the highlights of the annual symposium of the Skin of Color Society, held right before the annual meeting, a presentation by Michael Tirgan, MD, who has treated patients with keloids for about 10 years.

Dr. Tirgan, an oncologist based in New York, has a large database and registry of patients and shared some interesting data at the symposium. “What he’s found is that those who come with the supermassive and massive keloids are those who have had the most surgery on their keloid,” Dr. McMichael said in a video interview at the meeting.

His findings shed light on what she described as “a new perspective in the way that we think about keloids” and a new approach to treatment – considering keloids as tumors – not just a scar.

Dr. McMichael had no relevant disclosures.

emechcatie@frontlinemedcom.com

ORLANDO – It may be time to start considering new options for treating keloids, according to Amy McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C.

At the annual meeting of the American Academy of Dermatology, Dr. McMichael discussed one of the highlights of the annual symposium of the Skin of Color Society, held right before the annual meeting, a presentation by Michael Tirgan, MD, who has treated patients with keloids for about 10 years.

Dr. Tirgan, an oncologist based in New York, has a large database and registry of patients and shared some interesting data at the symposium. “What he’s found is that those who come with the supermassive and massive keloids are those who have had the most surgery on their keloid,” Dr. McMichael said in a video interview at the meeting.

His findings shed light on what she described as “a new perspective in the way that we think about keloids” and a new approach to treatment – considering keloids as tumors – not just a scar.

Dr. McMichael had no relevant disclosures.

emechcatie@frontlinemedcom.com

RIVIERA BEACH, FL—A comprehensive, interdisciplinary rehabilitation program for functional movement disorders (FMD) is providing high rates of sustained improvement in patients with this challenging clinical problem, according to an initial analysis. In this program, which is administered during a one-week in-hospital stay, the emphasis is on relearning normal movement through physical therapy, but attention is also paid to the psychological component of the disorder.

What Is FMD?

FMD includes movement abnormalities such as tremor, gait disturbances, or dystonia that are not explained by organic lesions or diseases. FMD is common and occurs in 3% to 5% of patients presenting at movement disorder clinics, according to Dr. LaFaver. Although FMD has an important psychogenic component, Dr. LaFaver said that the symptoms can be as persistent and debilitating as those associated with organic disorders. As with organic diseases, the consequences of FMD include chronic disability.

This last point was emphasized in the demographics of a series of 32 patients with FMD presented by Dr. LaFaver. The mean duration of symptoms was seven years, and 56% of patients were on disability at the time of enrollment into the MoRe program. Consistent with other series of patients with FMD, the population was predominantly female (75%), and a substantial proportion reported posttraumatic stress disorder (53%), sexual abuse (48%), and physical abuse (41%). Mean scores on the Beck Depression Inventory (16.59) and the State-Trait Anxiety Index (40.79) indicated that mood disorders were common. This result also has been previously reported in patients with FMD.

The MoRe Program

Over the course of the inpatient MoRe program, patients begin with simple, repetitive, and structured exercises relevant to their FMD, progressing to more complex motor tasks as they improve. Positive gains with physical therapy, which is provided for five consecutive days, are reinforced with structured cognitive behavioral therapy (CBT). The motor reprogramming provided is analogous to that offered for various neurologic symptoms associated with organic diseases, such as paraplegia or hemiparesis. Importantly, participants in the MoRe program are encouraged to think of their disorder as definable and treatable, even if the psychogenic component is not concealed.

“We do set the expectation that they will be normal by the end of the week,” said Dr. LaFaver, who explains to patients that neurologic abnormalities are likely to be involved, even if they cannot be objectively demonstrated.

MoRe is run as an inpatient program to permit an adequate intensity of physical therapy and to allow patients to develop trust in their physical and psychological therapists, Dr. LaFaver said. She also suggested that the emphasis on physical therapy in the MoRe program allows patients to frame the goals of treatment in a useful way. The psychological support is essentially adjunctive.

“It can be helpful to use analogies, such as describing the movement disorder as a software [problem] rather than a hardware problem,” Dr. LaFaver explained. The emphasis is on engaging patients to participate in treatment that will reverse adverse changes in the neurologic circuitry that is driving the symptoms. Citing recent functional MRI (fMRI) studies that have shown changes in right temporoparietal junction connectivity in patients with FMD, Dr. LaFaver suggested that the premise of a change in brain function with FMD has evidential support.

Rehabilitation Yields Improvements

In the series of 32 patients treated during a two-year period starting in 2014, the predominant symptoms were abnormal gait in 31%, dystonia in 31%, tremor in 13%, chorea in 13%, myoclonus in 6%, and weakness in 6%. On video rating performed by a movement disorder specialist to compare symptom severity at baseline with that following treatment, movement symptoms improved by 59% on average from day 1 to day 5 of treatment.

The improvement in video ratings was supported by patient self-assessment. On a descending scale of 7 to 1, with 1 signifying the greatest symptom control, the mean patient-assessment score was 2.07 immediately after completing the MoRe program and 2.78 at the six-month follow-up, according to Dr. LaFaver.

Patient satisfaction with the program was high. On an ascending scale of 0 to 10, with 10 providing the best rating, patients gave physical therapy an average rating of 9.23 and psychological skills training an average rating of 8.87. For mental practice training, another aspect of the MoRe program used to reinforce motor reprogramming, the average patient rating was 8.62. Ninety-six percent of patients reported that they would participate in the program again.

Taking a Systematic Approach

Patient selection is important, according to Dr. LaFaver. Although she does not believe it is necessary to rule out all organic diseases with an exhaustive series of diagnostic studies, she did suggest that a movement disorder specialist capable of performing a detailed differential diagnosis should be engaged to confirm FMD. She also suggested that patients are more likely to respond to a program like MoRe after they have accepted a diagnosis of FMD over other potential etiologies, such as Lyme disease.

So far, patients accepted into the MoRe program have typically had significant disability, which has facilitated the justification for inpatient treatment, according to Dr. LaFaver. As a result, third-party reimbursement is usually obtained. For patients with lower symptom burden, such as isolated tremor, similar principles have been employed in an outpatient basis with encouraging rates of response, said Dr. LaFaver. These responses emphasize the value of a systematic approach to a condition that deserves greater public awareness, as well as further clinical research, she added.

Even if FMD is primarily a psychogenic disorder, “patients treated with psychotherapy alone often do not get better,” Dr. LaFaver observed. “It is our job as neurologists to try to make a difference for these patients,” she added. She believes that the principles employed in the MoRe program, many of which were borrowed from an outpatient program at the Mayo Clinic in Rochester, Minnesota (where Dr. LaFaver trained), are broadly applicable in FMD.

Dr. LaFaver reported participation in studies of Parkinson’s disease and Huntington’s disease that had been sponsored by industry and by the NIH, but had no disclosures relevant to FMD.

—Theodore Bosworth

RIVIERA BEACH, FL—A comprehensive, interdisciplinary rehabilitation program for functional movement disorders (FMD) is providing high rates of sustained improvement in patients with this challenging clinical problem, according to an initial analysis. In this program, which is administered during a one-week in-hospital stay, the emphasis is on relearning normal movement through physical therapy, but attention is also paid to the psychological component of the disorder.

What Is FMD?

FMD includes movement abnormalities such as tremor, gait disturbances, or dystonia that are not explained by organic lesions or diseases. FMD is common and occurs in 3% to 5% of patients presenting at movement disorder clinics, according to Dr. LaFaver. Although FMD has an important psychogenic component, Dr. LaFaver said that the symptoms can be as persistent and debilitating as those associated with organic disorders. As with organic diseases, the consequences of FMD include chronic disability.

This last point was emphasized in the demographics of a series of 32 patients with FMD presented by Dr. LaFaver. The mean duration of symptoms was seven years, and 56% of patients were on disability at the time of enrollment into the MoRe program. Consistent with other series of patients with FMD, the population was predominantly female (75%), and a substantial proportion reported posttraumatic stress disorder (53%), sexual abuse (48%), and physical abuse (41%). Mean scores on the Beck Depression Inventory (16.59) and the State-Trait Anxiety Index (40.79) indicated that mood disorders were common. This result also has been previously reported in patients with FMD.

The MoRe Program

Over the course of the inpatient MoRe program, patients begin with simple, repetitive, and structured exercises relevant to their FMD, progressing to more complex motor tasks as they improve. Positive gains with physical therapy, which is provided for five consecutive days, are reinforced with structured cognitive behavioral therapy (CBT). The motor reprogramming provided is analogous to that offered for various neurologic symptoms associated with organic diseases, such as paraplegia or hemiparesis. Importantly, participants in the MoRe program are encouraged to think of their disorder as definable and treatable, even if the psychogenic component is not concealed.

“We do set the expectation that they will be normal by the end of the week,” said Dr. LaFaver, who explains to patients that neurologic abnormalities are likely to be involved, even if they cannot be objectively demonstrated.

MoRe is run as an inpatient program to permit an adequate intensity of physical therapy and to allow patients to develop trust in their physical and psychological therapists, Dr. LaFaver said. She also suggested that the emphasis on physical therapy in the MoRe program allows patients to frame the goals of treatment in a useful way. The psychological support is essentially adjunctive.

“It can be helpful to use analogies, such as describing the movement disorder as a software [problem] rather than a hardware problem,” Dr. LaFaver explained. The emphasis is on engaging patients to participate in treatment that will reverse adverse changes in the neurologic circuitry that is driving the symptoms. Citing recent functional MRI (fMRI) studies that have shown changes in right temporoparietal junction connectivity in patients with FMD, Dr. LaFaver suggested that the premise of a change in brain function with FMD has evidential support.

Rehabilitation Yields Improvements

In the series of 32 patients treated during a two-year period starting in 2014, the predominant symptoms were abnormal gait in 31%, dystonia in 31%, tremor in 13%, chorea in 13%, myoclonus in 6%, and weakness in 6%. On video rating performed by a movement disorder specialist to compare symptom severity at baseline with that following treatment, movement symptoms improved by 59% on average from day 1 to day 5 of treatment.

The improvement in video ratings was supported by patient self-assessment. On a descending scale of 7 to 1, with 1 signifying the greatest symptom control, the mean patient-assessment score was 2.07 immediately after completing the MoRe program and 2.78 at the six-month follow-up, according to Dr. LaFaver.

Patient satisfaction with the program was high. On an ascending scale of 0 to 10, with 10 providing the best rating, patients gave physical therapy an average rating of 9.23 and psychological skills training an average rating of 8.87. For mental practice training, another aspect of the MoRe program used to reinforce motor reprogramming, the average patient rating was 8.62. Ninety-six percent of patients reported that they would participate in the program again.

Taking a Systematic Approach

Patient selection is important, according to Dr. LaFaver. Although she does not believe it is necessary to rule out all organic diseases with an exhaustive series of diagnostic studies, she did suggest that a movement disorder specialist capable of performing a detailed differential diagnosis should be engaged to confirm FMD. She also suggested that patients are more likely to respond to a program like MoRe after they have accepted a diagnosis of FMD over other potential etiologies, such as Lyme disease.

So far, patients accepted into the MoRe program have typically had significant disability, which has facilitated the justification for inpatient treatment, according to Dr. LaFaver. As a result, third-party reimbursement is usually obtained. For patients with lower symptom burden, such as isolated tremor, similar principles have been employed in an outpatient basis with encouraging rates of response, said Dr. LaFaver. These responses emphasize the value of a systematic approach to a condition that deserves greater public awareness, as well as further clinical research, she added.

Even if FMD is primarily a psychogenic disorder, “patients treated with psychotherapy alone often do not get better,” Dr. LaFaver observed. “It is our job as neurologists to try to make a difference for these patients,” she added. She believes that the principles employed in the MoRe program, many of which were borrowed from an outpatient program at the Mayo Clinic in Rochester, Minnesota (where Dr. LaFaver trained), are broadly applicable in FMD.

Dr. LaFaver reported participation in studies of Parkinson’s disease and Huntington’s disease that had been sponsored by industry and by the NIH, but had no disclosures relevant to FMD.

—Theodore Bosworth

RIVIERA BEACH, FL—A comprehensive, interdisciplinary rehabilitation program for functional movement disorders (FMD) is providing high rates of sustained improvement in patients with this challenging clinical problem, according to an initial analysis. In this program, which is administered during a one-week in-hospital stay, the emphasis is on relearning normal movement through physical therapy, but attention is also paid to the psychological component of the disorder.

What Is FMD?

FMD includes movement abnormalities such as tremor, gait disturbances, or dystonia that are not explained by organic lesions or diseases. FMD is common and occurs in 3% to 5% of patients presenting at movement disorder clinics, according to Dr. LaFaver. Although FMD has an important psychogenic component, Dr. LaFaver said that the symptoms can be as persistent and debilitating as those associated with organic disorders. As with organic diseases, the consequences of FMD include chronic disability.

This last point was emphasized in the demographics of a series of 32 patients with FMD presented by Dr. LaFaver. The mean duration of symptoms was seven years, and 56% of patients were on disability at the time of enrollment into the MoRe program. Consistent with other series of patients with FMD, the population was predominantly female (75%), and a substantial proportion reported posttraumatic stress disorder (53%), sexual abuse (48%), and physical abuse (41%). Mean scores on the Beck Depression Inventory (16.59) and the State-Trait Anxiety Index (40.79) indicated that mood disorders were common. This result also has been previously reported in patients with FMD.

The MoRe Program

Over the course of the inpatient MoRe program, patients begin with simple, repetitive, and structured exercises relevant to their FMD, progressing to more complex motor tasks as they improve. Positive gains with physical therapy, which is provided for five consecutive days, are reinforced with structured cognitive behavioral therapy (CBT). The motor reprogramming provided is analogous to that offered for various neurologic symptoms associated with organic diseases, such as paraplegia or hemiparesis. Importantly, participants in the MoRe program are encouraged to think of their disorder as definable and treatable, even if the psychogenic component is not concealed.

“We do set the expectation that they will be normal by the end of the week,” said Dr. LaFaver, who explains to patients that neurologic abnormalities are likely to be involved, even if they cannot be objectively demonstrated.

MoRe is run as an inpatient program to permit an adequate intensity of physical therapy and to allow patients to develop trust in their physical and psychological therapists, Dr. LaFaver said. She also suggested that the emphasis on physical therapy in the MoRe program allows patients to frame the goals of treatment in a useful way. The psychological support is essentially adjunctive.

“It can be helpful to use analogies, such as describing the movement disorder as a software [problem] rather than a hardware problem,” Dr. LaFaver explained. The emphasis is on engaging patients to participate in treatment that will reverse adverse changes in the neurologic circuitry that is driving the symptoms. Citing recent functional MRI (fMRI) studies that have shown changes in right temporoparietal junction connectivity in patients with FMD, Dr. LaFaver suggested that the premise of a change in brain function with FMD has evidential support.

Rehabilitation Yields Improvements

In the series of 32 patients treated during a two-year period starting in 2014, the predominant symptoms were abnormal gait in 31%, dystonia in 31%, tremor in 13%, chorea in 13%, myoclonus in 6%, and weakness in 6%. On video rating performed by a movement disorder specialist to compare symptom severity at baseline with that following treatment, movement symptoms improved by 59% on average from day 1 to day 5 of treatment.

The improvement in video ratings was supported by patient self-assessment. On a descending scale of 7 to 1, with 1 signifying the greatest symptom control, the mean patient-assessment score was 2.07 immediately after completing the MoRe program and 2.78 at the six-month follow-up, according to Dr. LaFaver.

Patient satisfaction with the program was high. On an ascending scale of 0 to 10, with 10 providing the best rating, patients gave physical therapy an average rating of 9.23 and psychological skills training an average rating of 8.87. For mental practice training, another aspect of the MoRe program used to reinforce motor reprogramming, the average patient rating was 8.62. Ninety-six percent of patients reported that they would participate in the program again.

Taking a Systematic Approach

Patient selection is important, according to Dr. LaFaver. Although she does not believe it is necessary to rule out all organic diseases with an exhaustive series of diagnostic studies, she did suggest that a movement disorder specialist capable of performing a detailed differential diagnosis should be engaged to confirm FMD. She also suggested that patients are more likely to respond to a program like MoRe after they have accepted a diagnosis of FMD over other potential etiologies, such as Lyme disease.

So far, patients accepted into the MoRe program have typically had significant disability, which has facilitated the justification for inpatient treatment, according to Dr. LaFaver. As a result, third-party reimbursement is usually obtained. For patients with lower symptom burden, such as isolated tremor, similar principles have been employed in an outpatient basis with encouraging rates of response, said Dr. LaFaver. These responses emphasize the value of a systematic approach to a condition that deserves greater public awareness, as well as further clinical research, she added.

Even if FMD is primarily a psychogenic disorder, “patients treated with psychotherapy alone often do not get better,” Dr. LaFaver observed. “It is our job as neurologists to try to make a difference for these patients,” she added. She believes that the principles employed in the MoRe program, many of which were borrowed from an outpatient program at the Mayo Clinic in Rochester, Minnesota (where Dr. LaFaver trained), are broadly applicable in FMD.

Dr. LaFaver reported participation in studies of Parkinson’s disease and Huntington’s disease that had been sponsored by industry and by the NIH, but had no disclosures relevant to FMD.

—Theodore Bosworth

To the Editor:
Collagenous and elastotic marginal plaques of the hands (CEMPHs) has several names including degenerative collagenous plaques of the hands, keratoelastoidosis marginalis, and digital papular calcific elastosis. This rare disorder is an acquired, slowly progressive, asymptomatic, dermal connective tissue abnormality that is underrecognized and underdiagnosed. Clinical presentation includes hyperkeratotic translucent papules arranged linearly on the radial aspect of the hands.

A 74-year-old woman described having "rough hands" of more than 20 years' duration. She presented with 4-cm wide longitudinal, erythematous, firm, depressed plaques along the lateral edge of the second finger and extending to the medial thumb in both hands (Figure 1). She had attempted multiple treatments by her primary care physician, including topical and oral medications unknown to the patient and light therapy, all without benefit over a period of several years. We have attempted salicylic acid 40%, clobetasol cream 0.05%, and emollient creams containing α-hydroxy acid. At best the condition fluctuated between a subtle raised scale at the edge to smooth and occasionally more red-pink, seemingly unrelated to any treatments.

The patient did not have plaques elsewhere on the body, and notably, the feet were clear. She did not have a history of repeated trauma to the hands and did not engage in manual labor. She denied excessive sun exposure, though she had Fitzpatrick skin type III and a history of multiple precancers and nonmelanoma skin cancers 7 years prior to presentation.

Histology of CEMPH reveals a hyperkeratotic epidermis with an avascular and acellular replacement of the superficial reticular dermis by haphazardly arranged, thickened collagen fibers (Figure 2A-2C). Collagen fibers were oriented perpendicularly to the epidermal surface. Intervening amorphous basophilic elastotic masses were present in the upper dermis with occasional calcification and degenerative elastic fibers (Figure 2D).

Collagenous and elastotic marginal plaques of the hands is a chronic, asymptomatic, sclerotic skin disorder described in a 1960 case series of 5 patients reported by Burks et al.¹ Although it has many names, the most common is CEMPH. Collagenous and elastotic marginal plaques of the hands most often presents in white men aged 50 to 60 years.² Patients typically are asymptomatic with plaques limited to the junction of the palmar and dorsal surfaces of the hands with only minimal intermittent stiffness around the flexor creases. Lesions begin as discrete yellow papules that coalesce to form hyperkeratotic linear plaques with occasional telangiectasia.³

The etiology of CEMPH is attributed to collagen and elastin degeneration by chronic actinic damage, pressure, or trauma.^4,5 The 3 stages of degeneration include an initial linear padded stage, an intermediate padded plaque stage, and an advanced padded hyperkeratotic plaque stage.⁴ Vascular compromise is seen from the enlarged and fused thickened collagen and elastic fibers that in turn lead to ischemic changes, hyperkeratosis with epidermal atrophy, and papillary dermis telangiectasia. Absence or weak expression of keratins 14 and 10 and strong expression of keratin 16 have been reported in the epidermis of CEMPH patients.⁴

Collagenous and elastotic marginal plaques of the hands do not have a specific treatment, as it is a benign, slowly progressive condition. Several treatments such as laser therapy, high-potency topical corticosteroids, topical tazarotene and tretinoin, oral isotretinoin, and cryotherapy have been tried with little long-term success.⁴ Moisturizing may help reduce fissuring, and patients are advised to avoid the sun and repeated trauma to the hands.

The differential diagnosis of CEMPH is summarized in the Table. Two genodermatoses—acrokeratoelastoidosis of Costa and focal acral hyperkeratosis—clinically resemble CEMPH. Acrokeratoelastoidosis of Costa is an autosomal-dominant condition that occurs without trauma in children and young adults. Histopathology shows orthokeratotic hyperkeratosis due to an overproduction of filaggrin in the granular layer of the epidermis. The reticular dermis shows basophilic, thick, curled and fragmented elastic fibers with dilated capillaries that can be seen with Weigert elastic, Verhoeff-van Gieson, or orcein stains. Focal acral hyperkeratosis occurs on the hands and feet, predominantly in black patients. On histology, the epidermis shows a characteristic orthohyperkeratosis, moderate acanthosis, and slight hypergranulosis with no dermal involvment.⁶

Chronic hyperkeratotic eczematous dermatitis is another common entity in the differential characterized by hyperkeratotic plaques that scale and fissure. Biopsy demonstrates a spongiotic acanthotic epidermis.^7,8

Psoriasis of the hands, specifically hyperkeratotic palmoplantar psoriasis, is associated with manual labor, similar to CEMPH. Histology shows epidermal hyperplasia; regular acanthosis; loss of the granular skin layer with prominent dermal capillaries; and a mixed dermal infiltrate of lymphocytes, macrophages, and neutrophils.⁹ Hyperkeratotic palmoplantar lichen planus presents with pruritic papules in the third and fifth decades of life. Histologically, hyperkeratosis, acanthosis, and wedge-shaped hypergranulosis with a lichenoid lymphocytic infiltration at the dermoepidermal junction is seen.¹⁰

Palmoplantar keratodermas due to inflammatory reactive dermatoses include callosities that develop in response to repeated trauma or friction on the skin. On histology, there is prominent hyperkeratosis and acanthosis with moderate papillomatosis.¹¹ Drug-related palmoplantar keratodermas such as those from arsenic exposure can lead to multiple, irregular, verrucous, keratotic, and pigmented lesions on the palms and soles. Histologically, atypical keratinocytes are seen in the epidermis with thick hyperkeratosis and vacuolated cells without solar elastosis.¹²

In conclusion, CEMPH is an underdiagnosed and underrecognized condition characterized by asymptomatic hyperkeratotic linear plaques along the medial aspect of the thumb and radial aspect of the index finger. It is important to keep CEMPH in mind when dealing with occupational cases of repeated long-term trauma or pressure to the hands as well as excessive sun exposure. It also is imperative to separate it from other diseases and avoid misdiagnosing this degenerative collagenous and elastotic disease as a malignant lesion. 

To the Editor:
Collagenous and elastotic marginal plaques of the hands (CEMPHs) has several names including degenerative collagenous plaques of the hands, keratoelastoidosis marginalis, and digital papular calcific elastosis. This rare disorder is an acquired, slowly progressive, asymptomatic, dermal connective tissue abnormality that is underrecognized and underdiagnosed. Clinical presentation includes hyperkeratotic translucent papules arranged linearly on the radial aspect of the hands.

A 74-year-old woman described having "rough hands" of more than 20 years' duration. She presented with 4-cm wide longitudinal, erythematous, firm, depressed plaques along the lateral edge of the second finger and extending to the medial thumb in both hands (Figure 1). She had attempted multiple treatments by her primary care physician, including topical and oral medications unknown to the patient and light therapy, all without benefit over a period of several years. We have attempted salicylic acid 40%, clobetasol cream 0.05%, and emollient creams containing α-hydroxy acid. At best the condition fluctuated between a subtle raised scale at the edge to smooth and occasionally more red-pink, seemingly unrelated to any treatments.

The patient did not have plaques elsewhere on the body, and notably, the feet were clear. She did not have a history of repeated trauma to the hands and did not engage in manual labor. She denied excessive sun exposure, though she had Fitzpatrick skin type III and a history of multiple precancers and nonmelanoma skin cancers 7 years prior to presentation.

Histology of CEMPH reveals a hyperkeratotic epidermis with an avascular and acellular replacement of the superficial reticular dermis by haphazardly arranged, thickened collagen fibers (Figure 2A-2C). Collagen fibers were oriented perpendicularly to the epidermal surface. Intervening amorphous basophilic elastotic masses were present in the upper dermis with occasional calcification and degenerative elastic fibers (Figure 2D).

Collagenous and elastotic marginal plaques of the hands is a chronic, asymptomatic, sclerotic skin disorder described in a 1960 case series of 5 patients reported by Burks et al.¹ Although it has many names, the most common is CEMPH. Collagenous and elastotic marginal plaques of the hands most often presents in white men aged 50 to 60 years.² Patients typically are asymptomatic with plaques limited to the junction of the palmar and dorsal surfaces of the hands with only minimal intermittent stiffness around the flexor creases. Lesions begin as discrete yellow papules that coalesce to form hyperkeratotic linear plaques with occasional telangiectasia.³

The etiology of CEMPH is attributed to collagen and elastin degeneration by chronic actinic damage, pressure, or trauma.^4,5 The 3 stages of degeneration include an initial linear padded stage, an intermediate padded plaque stage, and an advanced padded hyperkeratotic plaque stage.⁴ Vascular compromise is seen from the enlarged and fused thickened collagen and elastic fibers that in turn lead to ischemic changes, hyperkeratosis with epidermal atrophy, and papillary dermis telangiectasia. Absence or weak expression of keratins 14 and 10 and strong expression of keratin 16 have been reported in the epidermis of CEMPH patients.⁴

Collagenous and elastotic marginal plaques of the hands do not have a specific treatment, as it is a benign, slowly progressive condition. Several treatments such as laser therapy, high-potency topical corticosteroids, topical tazarotene and tretinoin, oral isotretinoin, and cryotherapy have been tried with little long-term success.⁴ Moisturizing may help reduce fissuring, and patients are advised to avoid the sun and repeated trauma to the hands.

The differential diagnosis of CEMPH is summarized in the Table. Two genodermatoses—acrokeratoelastoidosis of Costa and focal acral hyperkeratosis—clinically resemble CEMPH. Acrokeratoelastoidosis of Costa is an autosomal-dominant condition that occurs without trauma in children and young adults. Histopathology shows orthokeratotic hyperkeratosis due to an overproduction of filaggrin in the granular layer of the epidermis. The reticular dermis shows basophilic, thick, curled and fragmented elastic fibers with dilated capillaries that can be seen with Weigert elastic, Verhoeff-van Gieson, or orcein stains. Focal acral hyperkeratosis occurs on the hands and feet, predominantly in black patients. On histology, the epidermis shows a characteristic orthohyperkeratosis, moderate acanthosis, and slight hypergranulosis with no dermal involvment.⁶

Chronic hyperkeratotic eczematous dermatitis is another common entity in the differential characterized by hyperkeratotic plaques that scale and fissure. Biopsy demonstrates a spongiotic acanthotic epidermis.^7,8

Psoriasis of the hands, specifically hyperkeratotic palmoplantar psoriasis, is associated with manual labor, similar to CEMPH. Histology shows epidermal hyperplasia; regular acanthosis; loss of the granular skin layer with prominent dermal capillaries; and a mixed dermal infiltrate of lymphocytes, macrophages, and neutrophils.⁹ Hyperkeratotic palmoplantar lichen planus presents with pruritic papules in the third and fifth decades of life. Histologically, hyperkeratosis, acanthosis, and wedge-shaped hypergranulosis with a lichenoid lymphocytic infiltration at the dermoepidermal junction is seen.¹⁰

Palmoplantar keratodermas due to inflammatory reactive dermatoses include callosities that develop in response to repeated trauma or friction on the skin. On histology, there is prominent hyperkeratosis and acanthosis with moderate papillomatosis.¹¹ Drug-related palmoplantar keratodermas such as those from arsenic exposure can lead to multiple, irregular, verrucous, keratotic, and pigmented lesions on the palms and soles. Histologically, atypical keratinocytes are seen in the epidermis with thick hyperkeratosis and vacuolated cells without solar elastosis.¹²

In conclusion, CEMPH is an underdiagnosed and underrecognized condition characterized by asymptomatic hyperkeratotic linear plaques along the medial aspect of the thumb and radial aspect of the index finger. It is important to keep CEMPH in mind when dealing with occupational cases of repeated long-term trauma or pressure to the hands as well as excessive sun exposure. It also is imperative to separate it from other diseases and avoid misdiagnosing this degenerative collagenous and elastotic disease as a malignant lesion. 

To the Editor:
Collagenous and elastotic marginal plaques of the hands (CEMPHs) has several names including degenerative collagenous plaques of the hands, keratoelastoidosis marginalis, and digital papular calcific elastosis. This rare disorder is an acquired, slowly progressive, asymptomatic, dermal connective tissue abnormality that is underrecognized and underdiagnosed. Clinical presentation includes hyperkeratotic translucent papules arranged linearly on the radial aspect of the hands.

A 74-year-old woman described having "rough hands" of more than 20 years' duration. She presented with 4-cm wide longitudinal, erythematous, firm, depressed plaques along the lateral edge of the second finger and extending to the medial thumb in both hands (Figure 1). She had attempted multiple treatments by her primary care physician, including topical and oral medications unknown to the patient and light therapy, all without benefit over a period of several years. We have attempted salicylic acid 40%, clobetasol cream 0.05%, and emollient creams containing α-hydroxy acid. At best the condition fluctuated between a subtle raised scale at the edge to smooth and occasionally more red-pink, seemingly unrelated to any treatments.

The patient did not have plaques elsewhere on the body, and notably, the feet were clear. She did not have a history of repeated trauma to the hands and did not engage in manual labor. She denied excessive sun exposure, though she had Fitzpatrick skin type III and a history of multiple precancers and nonmelanoma skin cancers 7 years prior to presentation.

Histology of CEMPH reveals a hyperkeratotic epidermis with an avascular and acellular replacement of the superficial reticular dermis by haphazardly arranged, thickened collagen fibers (Figure 2A-2C). Collagen fibers were oriented perpendicularly to the epidermal surface. Intervening amorphous basophilic elastotic masses were present in the upper dermis with occasional calcification and degenerative elastic fibers (Figure 2D).

Collagenous and elastotic marginal plaques of the hands is a chronic, asymptomatic, sclerotic skin disorder described in a 1960 case series of 5 patients reported by Burks et al.¹ Although it has many names, the most common is CEMPH. Collagenous and elastotic marginal plaques of the hands most often presents in white men aged 50 to 60 years.² Patients typically are asymptomatic with plaques limited to the junction of the palmar and dorsal surfaces of the hands with only minimal intermittent stiffness around the flexor creases. Lesions begin as discrete yellow papules that coalesce to form hyperkeratotic linear plaques with occasional telangiectasia.³

The etiology of CEMPH is attributed to collagen and elastin degeneration by chronic actinic damage, pressure, or trauma.^4,5 The 3 stages of degeneration include an initial linear padded stage, an intermediate padded plaque stage, and an advanced padded hyperkeratotic plaque stage.⁴ Vascular compromise is seen from the enlarged and fused thickened collagen and elastic fibers that in turn lead to ischemic changes, hyperkeratosis with epidermal atrophy, and papillary dermis telangiectasia. Absence or weak expression of keratins 14 and 10 and strong expression of keratin 16 have been reported in the epidermis of CEMPH patients.⁴

Collagenous and elastotic marginal plaques of the hands do not have a specific treatment, as it is a benign, slowly progressive condition. Several treatments such as laser therapy, high-potency topical corticosteroids, topical tazarotene and tretinoin, oral isotretinoin, and cryotherapy have been tried with little long-term success.⁴ Moisturizing may help reduce fissuring, and patients are advised to avoid the sun and repeated trauma to the hands.

The differential diagnosis of CEMPH is summarized in the Table. Two genodermatoses—acrokeratoelastoidosis of Costa and focal acral hyperkeratosis—clinically resemble CEMPH. Acrokeratoelastoidosis of Costa is an autosomal-dominant condition that occurs without trauma in children and young adults. Histopathology shows orthokeratotic hyperkeratosis due to an overproduction of filaggrin in the granular layer of the epidermis. The reticular dermis shows basophilic, thick, curled and fragmented elastic fibers with dilated capillaries that can be seen with Weigert elastic, Verhoeff-van Gieson, or orcein stains. Focal acral hyperkeratosis occurs on the hands and feet, predominantly in black patients. On histology, the epidermis shows a characteristic orthohyperkeratosis, moderate acanthosis, and slight hypergranulosis with no dermal involvment.⁶

Chronic hyperkeratotic eczematous dermatitis is another common entity in the differential characterized by hyperkeratotic plaques that scale and fissure. Biopsy demonstrates a spongiotic acanthotic epidermis.^7,8

Psoriasis of the hands, specifically hyperkeratotic palmoplantar psoriasis, is associated with manual labor, similar to CEMPH. Histology shows epidermal hyperplasia; regular acanthosis; loss of the granular skin layer with prominent dermal capillaries; and a mixed dermal infiltrate of lymphocytes, macrophages, and neutrophils.⁹ Hyperkeratotic palmoplantar lichen planus presents with pruritic papules in the third and fifth decades of life. Histologically, hyperkeratosis, acanthosis, and wedge-shaped hypergranulosis with a lichenoid lymphocytic infiltration at the dermoepidermal junction is seen.¹⁰

Palmoplantar keratodermas due to inflammatory reactive dermatoses include callosities that develop in response to repeated trauma or friction on the skin. On histology, there is prominent hyperkeratosis and acanthosis with moderate papillomatosis.¹¹ Drug-related palmoplantar keratodermas such as those from arsenic exposure can lead to multiple, irregular, verrucous, keratotic, and pigmented lesions on the palms and soles. Histologically, atypical keratinocytes are seen in the epidermis with thick hyperkeratosis and vacuolated cells without solar elastosis.¹²

In conclusion, CEMPH is an underdiagnosed and underrecognized condition characterized by asymptomatic hyperkeratotic linear plaques along the medial aspect of the thumb and radial aspect of the index finger. It is important to keep CEMPH in mind when dealing with occupational cases of repeated long-term trauma or pressure to the hands as well as excessive sun exposure. It also is imperative to separate it from other diseases and avoid misdiagnosing this degenerative collagenous and elastotic disease as a malignant lesion.