Dermatology News

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

PORTLAND, ORE. – About 10 years ago when Arash Mostaghimi, MD, MPA, MPH, became an attending physician at Brigham and Women’s Hospital, Boston, he noticed that some of his dermatology colleagues checked the potassium levels religiously in their female patients taking spironolactone, while others never did.

“It led to this question: should we check potassium in healthy young women starting spironolactone for acne?” Dr. Mostaghimi, director of the dermatology inpatient service at Brigham and Women’s, said at the annual meeting of the Pacific Dermatologic Association.

To find out, he and his colleagues reviewed 1,802 serum potassium measurements in a study of healthy young women with no known health conditions who were taking spironolactone, published in 2015. They discovered that 13 of those tests suggested mild hyperkalemia, defined as a level greater than 5.0 mEq/L. Of these, six were rechecked and were normal; no action was taken in the other seven patients.

“This led us to conclude that we spent $78,000 at our institution on testing that did not appear to yield clinically significant information for these patients, and that routine potassium monitoring is unnecessary for most women taking spironolactone for acne,” he said. Their findings have been validated “in many cohorts of data,” he added.

The study serves as an example of efforts dermatologists can take to curb unnecessary costs within the field to be “appropriate stewards of resources,” he continued. “We have to think about the ratio of benefit over cost. It’s not just about the cost, it’s about what you’re getting for the amount of money that you’re spending. The idea of this is not restricting or not giving people medications or access to things that they need. The idea is to do it in a thoughtful way that works across the population.”
 

Value thresholds

Determining the value thresholds of a particular medicine or procedure is also essential to good dermatology practice. To illustrate, Dr. Mostaghimi cited a prospective cohort study that compared treatment patterns and clinical outcomes in 1,536 consecutive patients with nonmelanoma skin cancer (NMSC) with and without limited life expectancy. More than two-thirds of the NMSCs (69%) were treated surgically. After adjusting for tumor and patient characteristics, the researchers found that 43% of patients with low life expectancy died within 5 years, but not from NMSC.

“Does that mean we shouldn’t do surgery for NMSC patients with low life expectancy?” he asked. “Should we do it less? Should we let the patients decide? It’s complicated. As a society, we have to decide what’s worth doing and what’s not worth doing,” he said. “What about old diseases with new treatments, like alopecia areata? Is alopecia areata a cosmetic condition? Dermatologists and patients wouldn’t classify it that way, but many insurers do. How do you negotiate that?”

In 2013, the American Academy of Dermatology identified 10 evidence-based recommendations that can support conversations between patients and dermatologists about treatments, tests, and procedures that may not be necessary. One of the recommendations was not to prescribe oral antifungal therapy for suspected nail fungus without confirmation of fungal infection.

“If a clinician thinks a patient has onychomycosis, he or she is usually right,” Dr. Mostaghimi said. “But what’s the added cost/benefit of performing a KOH followed by PAS testing if negative or performing a PAS test directly versus just treating the patient?”

In 2006, he and his colleagues published the results of a decision analysis to address these questions. They determined that the costs of testing to avoid one case of clinically apparent liver injury with terbinafine treatment was $18.2-$43.7 million for the KOH screening pathway and $37.6 to $90.2 million for the PAS testing pathway.

“Is that worth it?” he asked. “Would we get more value for spending the money elsewhere? In this case, the answer is most likely yes.”

Isotretinoin lab testing

Translating research into recommendations and standards of care is one way to help curb costs in dermatology. As an example, he cited lab monitoring for patients treated with isotretinoin for acne.

“There have been a number of papers over the years that have suggested that the number of labs we do is excessive, that the value that they provide is low, and that abnormal results do not impact our decision-making,” Dr. Mostaghimi said. “Do some patients on isotretinoin get mildly elevated [liver function tests] and hypertriglyceridemia? Yes, that happens. Does it matter? Nothing has demonstrated that it matters. Does it matter that an 18-year-old has high triglycerides for 6 months? Rarely, if ever.”

To promote a new approach, he and a panel of acne experts from five continents performed a Delphi consensus study. Based on their consensus, they proposed a simple approach: For “generally healthy patients without underlying abnormalities or preexisting conditions warranting further investigation,” check ALT and triglycerides prior to initiating isotretinoin. Then start isotretinoin.

“At the peak dose, recheck ALT and triglycerides – this might be at month 2,” Dr. Mostaghimi said. “Other people wait a little bit longer. No labs are required once treatment is complete. Of course, adjust this approach based on your assessment of the patient in front of you. None of these recommendations should replace your clinical judgment and intuition.”

He proposed a new paradigm where dermatologists can ask themselves three questions for every patient they see: Why is this intervention or test being done? Why is it being done in this patient? And why do it at that time? “If we think this way, we can identify some inconsistencies in our own thinking and opportunities for improvement,” he said.

Dr. Mostaghimi reported that he is a consultant to Pfizer, Concert, Lilly, and Bioniz. He is also an advisor to Him & Hers Cosmetics and Digital Diagnostics and is an associate editor for JAMA Dermatology.

PORTLAND, ORE. – About 10 years ago when Arash Mostaghimi, MD, MPA, MPH, became an attending physician at Brigham and Women’s Hospital, Boston, he noticed that some of his dermatology colleagues checked the potassium levels religiously in their female patients taking spironolactone, while others never did.

“It led to this question: should we check potassium in healthy young women starting spironolactone for acne?” Dr. Mostaghimi, director of the dermatology inpatient service at Brigham and Women’s, said at the annual meeting of the Pacific Dermatologic Association.

To find out, he and his colleagues reviewed 1,802 serum potassium measurements in a study of healthy young women with no known health conditions who were taking spironolactone, published in 2015. They discovered that 13 of those tests suggested mild hyperkalemia, defined as a level greater than 5.0 mEq/L. Of these, six were rechecked and were normal; no action was taken in the other seven patients.

“This led us to conclude that we spent $78,000 at our institution on testing that did not appear to yield clinically significant information for these patients, and that routine potassium monitoring is unnecessary for most women taking spironolactone for acne,” he said. Their findings have been validated “in many cohorts of data,” he added.

The study serves as an example of efforts dermatologists can take to curb unnecessary costs within the field to be “appropriate stewards of resources,” he continued. “We have to think about the ratio of benefit over cost. It’s not just about the cost, it’s about what you’re getting for the amount of money that you’re spending. The idea of this is not restricting or not giving people medications or access to things that they need. The idea is to do it in a thoughtful way that works across the population.”
 

Value thresholds

Determining the value thresholds of a particular medicine or procedure is also essential to good dermatology practice. To illustrate, Dr. Mostaghimi cited a prospective cohort study that compared treatment patterns and clinical outcomes in 1,536 consecutive patients with nonmelanoma skin cancer (NMSC) with and without limited life expectancy. More than two-thirds of the NMSCs (69%) were treated surgically. After adjusting for tumor and patient characteristics, the researchers found that 43% of patients with low life expectancy died within 5 years, but not from NMSC.

“Does that mean we shouldn’t do surgery for NMSC patients with low life expectancy?” he asked. “Should we do it less? Should we let the patients decide? It’s complicated. As a society, we have to decide what’s worth doing and what’s not worth doing,” he said. “What about old diseases with new treatments, like alopecia areata? Is alopecia areata a cosmetic condition? Dermatologists and patients wouldn’t classify it that way, but many insurers do. How do you negotiate that?”

In 2013, the American Academy of Dermatology identified 10 evidence-based recommendations that can support conversations between patients and dermatologists about treatments, tests, and procedures that may not be necessary. One of the recommendations was not to prescribe oral antifungal therapy for suspected nail fungus without confirmation of fungal infection.

“If a clinician thinks a patient has onychomycosis, he or she is usually right,” Dr. Mostaghimi said. “But what’s the added cost/benefit of performing a KOH followed by PAS testing if negative or performing a PAS test directly versus just treating the patient?”

In 2006, he and his colleagues published the results of a decision analysis to address these questions. They determined that the costs of testing to avoid one case of clinically apparent liver injury with terbinafine treatment was $18.2-$43.7 million for the KOH screening pathway and $37.6 to $90.2 million for the PAS testing pathway.

“Is that worth it?” he asked. “Would we get more value for spending the money elsewhere? In this case, the answer is most likely yes.”

Isotretinoin lab testing

Translating research into recommendations and standards of care is one way to help curb costs in dermatology. As an example, he cited lab monitoring for patients treated with isotretinoin for acne.

“There have been a number of papers over the years that have suggested that the number of labs we do is excessive, that the value that they provide is low, and that abnormal results do not impact our decision-making,” Dr. Mostaghimi said. “Do some patients on isotretinoin get mildly elevated [liver function tests] and hypertriglyceridemia? Yes, that happens. Does it matter? Nothing has demonstrated that it matters. Does it matter that an 18-year-old has high triglycerides for 6 months? Rarely, if ever.”

To promote a new approach, he and a panel of acne experts from five continents performed a Delphi consensus study. Based on their consensus, they proposed a simple approach: For “generally healthy patients without underlying abnormalities or preexisting conditions warranting further investigation,” check ALT and triglycerides prior to initiating isotretinoin. Then start isotretinoin.

“At the peak dose, recheck ALT and triglycerides – this might be at month 2,” Dr. Mostaghimi said. “Other people wait a little bit longer. No labs are required once treatment is complete. Of course, adjust this approach based on your assessment of the patient in front of you. None of these recommendations should replace your clinical judgment and intuition.”

He proposed a new paradigm where dermatologists can ask themselves three questions for every patient they see: Why is this intervention or test being done? Why is it being done in this patient? And why do it at that time? “If we think this way, we can identify some inconsistencies in our own thinking and opportunities for improvement,” he said.

Dr. Mostaghimi reported that he is a consultant to Pfizer, Concert, Lilly, and Bioniz. He is also an advisor to Him & Hers Cosmetics and Digital Diagnostics and is an associate editor for JAMA Dermatology.

PORTLAND, ORE. – About 10 years ago when Arash Mostaghimi, MD, MPA, MPH, became an attending physician at Brigham and Women’s Hospital, Boston, he noticed that some of his dermatology colleagues checked the potassium levels religiously in their female patients taking spironolactone, while others never did.

“It led to this question: should we check potassium in healthy young women starting spironolactone for acne?” Dr. Mostaghimi, director of the dermatology inpatient service at Brigham and Women’s, said at the annual meeting of the Pacific Dermatologic Association.

To find out, he and his colleagues reviewed 1,802 serum potassium measurements in a study of healthy young women with no known health conditions who were taking spironolactone, published in 2015. They discovered that 13 of those tests suggested mild hyperkalemia, defined as a level greater than 5.0 mEq/L. Of these, six were rechecked and were normal; no action was taken in the other seven patients.

“This led us to conclude that we spent $78,000 at our institution on testing that did not appear to yield clinically significant information for these patients, and that routine potassium monitoring is unnecessary for most women taking spironolactone for acne,” he said. Their findings have been validated “in many cohorts of data,” he added.

The study serves as an example of efforts dermatologists can take to curb unnecessary costs within the field to be “appropriate stewards of resources,” he continued. “We have to think about the ratio of benefit over cost. It’s not just about the cost, it’s about what you’re getting for the amount of money that you’re spending. The idea of this is not restricting or not giving people medications or access to things that they need. The idea is to do it in a thoughtful way that works across the population.”
 

Value thresholds

Determining the value thresholds of a particular medicine or procedure is also essential to good dermatology practice. To illustrate, Dr. Mostaghimi cited a prospective cohort study that compared treatment patterns and clinical outcomes in 1,536 consecutive patients with nonmelanoma skin cancer (NMSC) with and without limited life expectancy. More than two-thirds of the NMSCs (69%) were treated surgically. After adjusting for tumor and patient characteristics, the researchers found that 43% of patients with low life expectancy died within 5 years, but not from NMSC.

“Does that mean we shouldn’t do surgery for NMSC patients with low life expectancy?” he asked. “Should we do it less? Should we let the patients decide? It’s complicated. As a society, we have to decide what’s worth doing and what’s not worth doing,” he said. “What about old diseases with new treatments, like alopecia areata? Is alopecia areata a cosmetic condition? Dermatologists and patients wouldn’t classify it that way, but many insurers do. How do you negotiate that?”

In 2013, the American Academy of Dermatology identified 10 evidence-based recommendations that can support conversations between patients and dermatologists about treatments, tests, and procedures that may not be necessary. One of the recommendations was not to prescribe oral antifungal therapy for suspected nail fungus without confirmation of fungal infection.

“If a clinician thinks a patient has onychomycosis, he or she is usually right,” Dr. Mostaghimi said. “But what’s the added cost/benefit of performing a KOH followed by PAS testing if negative or performing a PAS test directly versus just treating the patient?”

In 2006, he and his colleagues published the results of a decision analysis to address these questions. They determined that the costs of testing to avoid one case of clinically apparent liver injury with terbinafine treatment was $18.2-$43.7 million for the KOH screening pathway and $37.6 to $90.2 million for the PAS testing pathway.

“Is that worth it?” he asked. “Would we get more value for spending the money elsewhere? In this case, the answer is most likely yes.”

Isotretinoin lab testing

Translating research into recommendations and standards of care is one way to help curb costs in dermatology. As an example, he cited lab monitoring for patients treated with isotretinoin for acne.

“There have been a number of papers over the years that have suggested that the number of labs we do is excessive, that the value that they provide is low, and that abnormal results do not impact our decision-making,” Dr. Mostaghimi said. “Do some patients on isotretinoin get mildly elevated [liver function tests] and hypertriglyceridemia? Yes, that happens. Does it matter? Nothing has demonstrated that it matters. Does it matter that an 18-year-old has high triglycerides for 6 months? Rarely, if ever.”

To promote a new approach, he and a panel of acne experts from five continents performed a Delphi consensus study. Based on their consensus, they proposed a simple approach: For “generally healthy patients without underlying abnormalities or preexisting conditions warranting further investigation,” check ALT and triglycerides prior to initiating isotretinoin. Then start isotretinoin.

“At the peak dose, recheck ALT and triglycerides – this might be at month 2,” Dr. Mostaghimi said. “Other people wait a little bit longer. No labs are required once treatment is complete. Of course, adjust this approach based on your assessment of the patient in front of you. None of these recommendations should replace your clinical judgment and intuition.”

He proposed a new paradigm where dermatologists can ask themselves three questions for every patient they see: Why is this intervention or test being done? Why is it being done in this patient? And why do it at that time? “If we think this way, we can identify some inconsistencies in our own thinking and opportunities for improvement,” he said.

Dr. Mostaghimi reported that he is a consultant to Pfizer, Concert, Lilly, and Bioniz. He is also an advisor to Him & Hers Cosmetics and Digital Diagnostics and is an associate editor for JAMA Dermatology.

A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.

According to the U.S. Centers of Disease Control and Prevention, the COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.

“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”

“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.

That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”

Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.

Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.

That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.

According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”

Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.

Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.

Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”

One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.

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

A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.

According to the U.S. Centers of Disease Control and Prevention, the COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.

“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”

“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.

That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”

Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.

Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.

That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.

According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”

Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.

Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.

Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”

One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.

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

A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.

According to the U.S. Centers of Disease Control and Prevention, the COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.

“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”

“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.

That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”

Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.

Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.

That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.

According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”

Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.

Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.

Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”

One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.

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

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

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

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

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

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

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

In a first-of-its-kind clinical trial, researchers in Germany used a cancer-killing cell therapy to successfully treat lupus in a small number of patients.

Their study, published online in Nature Medicine, included five patients with systemic lupus erythematosus (SLE). All of the patients were treated with chimeric antigen receptor (CAR) T-cell therapy, a treatment regularly used to kill cancer cells. Researchers harvested the patients’ immune cells and engineered them to destroy dysfunctional cells when infused back into the body.

The five patients – all of whom had an aggressive form of the autoimmune disease – underwent a single infusion of the experimental treatment. All five patients were able to stop their standard treatments for as long as 17 months following the therapy, the study found. The patients also stopped experiencing severe symptoms such as lung inflammation, fibrosis of the heart valves, arthritis, and fatigue. The patients have not relapsed.

“Our data reveal unexpected insights for a role of CAR T cells in nonmalignant diseases that could provide new opportunities for the treatment of autoimmune disease,” the study authors wrote.

Lupus is a chronic inflammatory disease in which the immune system attacks the body’s own cells. Both antibody-producing B and T cells in individuals with lupus become overactive, which can lead to a flare of symptoms that range from mild pain and fatigue to life-threatening inflammation and tissue damage. They are often treated with medications that deplete their B cells or change the way they function to help wipe out infected cells.

The approach used by the study researchers is similar to monoclonal antibody therapies that destroy dysfunctional B cells, such as rituximab (Rituxan and biosimilars) and obinutuzumab (Gazyva), according to Michael Belmont, MD, codirector of New York University’s Lupus Center and medical director of Bellevue Hospital Lupus Clinic, also in New York.

“Previously, this has been accomplished with monoclonal antibodies that target surface markers on B cells and results in their removal,” said Dr. Belmont, who was not connected to the study. “The report describes a novel approach that harnesses a patient’s own T cells, another type of white blood cell, to eliminate that patient’s own B cells.”

Preclinical studies involving mice previously showed that CAR T-cell therapy could help to reset the immune system. However, this latest study also found that patients did not need to continue any of their previous therapies, even after they regained their B cells about 4 months after the therapy.

“A deep depletion of CD19+ B cells and plasmablasts in the tissues could trigger an immune reset in SLE that could allow the cessation of immunosuppressive treatment,” said Mehrnaz Hojjati, MD, a rheumatologist and director of rheumatology operations at Loma Linda (Calif.) University Health. Dr. Hojjati was not affiliated with the study.

While the single-treatment therapy is promising, transfused T cells do carry risks. Some of the patients in the study experienced fever and muscle pain following the procedure, the authors noted. Dr. Belmont said more serious risks for this kind of therapy may include organ injury.

“This treatment can [also] increase incidence, for example, of pneumonia or shingles,” he said.

The study authors initially documented their work in a correspondence published in August 2021 in the New England Journal of Medicine. At that time, they reported that a 20-year-old woman with a severe refractory SLE went into remission following the treatment.

The five patients in the current study – four women and one man – were aged 18-24 years. All of the patients had previously been treated with several immunosuppressive medications, the study authors noted.

“This is an exciting approach, but many more patients need to be treated to really understand the efficacy and safety,” Dr. Belmont said.

Experts, including Dr. Belmont, also said the procedure is also costly and requires access to labs that can engineer a patient’s own T cells after they’ve been donated.

“The entire process must maintain sterility to avoid contamination, which would be harmful when reinfused into the patient,” he said.

According to Arthur Kavanaugh, MD, professor of medicine at UC San Diego Health, this form of therapy may be an option for severe refractory patients who have not responded well to other more established therapies.

“[It’s] exciting data, but very intense and so not likely to be something for an average patient in the near future,” said Dr. Kavanaugh, who was not affiliated with the study.

The study authors say they intend to create a larger trial to further explore which type of patient may benefit the most from this treatment, and for how long.

The study was supported by the German Research Foundation, the German Federal Ministry of Education and Research, the European Union, and the Innovative Medicines Initiative–funded project, Rheuma Tolerance for Cure. The study received no commercial funding, and the authors said they had no competing interests related to the study. None of the experts interviewed reported relevant financial relationships.

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

In a first-of-its-kind clinical trial, researchers in Germany used a cancer-killing cell therapy to successfully treat lupus in a small number of patients.

Their study, published online in Nature Medicine, included five patients with systemic lupus erythematosus (SLE). All of the patients were treated with chimeric antigen receptor (CAR) T-cell therapy, a treatment regularly used to kill cancer cells. Researchers harvested the patients’ immune cells and engineered them to destroy dysfunctional cells when infused back into the body.

The five patients – all of whom had an aggressive form of the autoimmune disease – underwent a single infusion of the experimental treatment. All five patients were able to stop their standard treatments for as long as 17 months following the therapy, the study found. The patients also stopped experiencing severe symptoms such as lung inflammation, fibrosis of the heart valves, arthritis, and fatigue. The patients have not relapsed.

“Our data reveal unexpected insights for a role of CAR T cells in nonmalignant diseases that could provide new opportunities for the treatment of autoimmune disease,” the study authors wrote.

Lupus is a chronic inflammatory disease in which the immune system attacks the body’s own cells. Both antibody-producing B and T cells in individuals with lupus become overactive, which can lead to a flare of symptoms that range from mild pain and fatigue to life-threatening inflammation and tissue damage. They are often treated with medications that deplete their B cells or change the way they function to help wipe out infected cells.

The approach used by the study researchers is similar to monoclonal antibody therapies that destroy dysfunctional B cells, such as rituximab (Rituxan and biosimilars) and obinutuzumab (Gazyva), according to Michael Belmont, MD, codirector of New York University’s Lupus Center and medical director of Bellevue Hospital Lupus Clinic, also in New York.

“Previously, this has been accomplished with monoclonal antibodies that target surface markers on B cells and results in their removal,” said Dr. Belmont, who was not connected to the study. “The report describes a novel approach that harnesses a patient’s own T cells, another type of white blood cell, to eliminate that patient’s own B cells.”

Preclinical studies involving mice previously showed that CAR T-cell therapy could help to reset the immune system. However, this latest study also found that patients did not need to continue any of their previous therapies, even after they regained their B cells about 4 months after the therapy.

“A deep depletion of CD19+ B cells and plasmablasts in the tissues could trigger an immune reset in SLE that could allow the cessation of immunosuppressive treatment,” said Mehrnaz Hojjati, MD, a rheumatologist and director of rheumatology operations at Loma Linda (Calif.) University Health. Dr. Hojjati was not affiliated with the study.

While the single-treatment therapy is promising, transfused T cells do carry risks. Some of the patients in the study experienced fever and muscle pain following the procedure, the authors noted. Dr. Belmont said more serious risks for this kind of therapy may include organ injury.

“This treatment can [also] increase incidence, for example, of pneumonia or shingles,” he said.

The study authors initially documented their work in a correspondence published in August 2021 in the New England Journal of Medicine. At that time, they reported that a 20-year-old woman with a severe refractory SLE went into remission following the treatment.

The five patients in the current study – four women and one man – were aged 18-24 years. All of the patients had previously been treated with several immunosuppressive medications, the study authors noted.

“This is an exciting approach, but many more patients need to be treated to really understand the efficacy and safety,” Dr. Belmont said.

Experts, including Dr. Belmont, also said the procedure is also costly and requires access to labs that can engineer a patient’s own T cells after they’ve been donated.

“The entire process must maintain sterility to avoid contamination, which would be harmful when reinfused into the patient,” he said.

According to Arthur Kavanaugh, MD, professor of medicine at UC San Diego Health, this form of therapy may be an option for severe refractory patients who have not responded well to other more established therapies.

“[It’s] exciting data, but very intense and so not likely to be something for an average patient in the near future,” said Dr. Kavanaugh, who was not affiliated with the study.

The study authors say they intend to create a larger trial to further explore which type of patient may benefit the most from this treatment, and for how long.

The study was supported by the German Research Foundation, the German Federal Ministry of Education and Research, the European Union, and the Innovative Medicines Initiative–funded project, Rheuma Tolerance for Cure. The study received no commercial funding, and the authors said they had no competing interests related to the study. None of the experts interviewed reported relevant financial relationships.

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

In a first-of-its-kind clinical trial, researchers in Germany used a cancer-killing cell therapy to successfully treat lupus in a small number of patients.

Their study, published online in Nature Medicine, included five patients with systemic lupus erythematosus (SLE). All of the patients were treated with chimeric antigen receptor (CAR) T-cell therapy, a treatment regularly used to kill cancer cells. Researchers harvested the patients’ immune cells and engineered them to destroy dysfunctional cells when infused back into the body.

The five patients – all of whom had an aggressive form of the autoimmune disease – underwent a single infusion of the experimental treatment. All five patients were able to stop their standard treatments for as long as 17 months following the therapy, the study found. The patients also stopped experiencing severe symptoms such as lung inflammation, fibrosis of the heart valves, arthritis, and fatigue. The patients have not relapsed.

“Our data reveal unexpected insights for a role of CAR T cells in nonmalignant diseases that could provide new opportunities for the treatment of autoimmune disease,” the study authors wrote.

Lupus is a chronic inflammatory disease in which the immune system attacks the body’s own cells. Both antibody-producing B and T cells in individuals with lupus become overactive, which can lead to a flare of symptoms that range from mild pain and fatigue to life-threatening inflammation and tissue damage. They are often treated with medications that deplete their B cells or change the way they function to help wipe out infected cells.

The approach used by the study researchers is similar to monoclonal antibody therapies that destroy dysfunctional B cells, such as rituximab (Rituxan and biosimilars) and obinutuzumab (Gazyva), according to Michael Belmont, MD, codirector of New York University’s Lupus Center and medical director of Bellevue Hospital Lupus Clinic, also in New York.

“Previously, this has been accomplished with monoclonal antibodies that target surface markers on B cells and results in their removal,” said Dr. Belmont, who was not connected to the study. “The report describes a novel approach that harnesses a patient’s own T cells, another type of white blood cell, to eliminate that patient’s own B cells.”

Preclinical studies involving mice previously showed that CAR T-cell therapy could help to reset the immune system. However, this latest study also found that patients did not need to continue any of their previous therapies, even after they regained their B cells about 4 months after the therapy.

“A deep depletion of CD19+ B cells and plasmablasts in the tissues could trigger an immune reset in SLE that could allow the cessation of immunosuppressive treatment,” said Mehrnaz Hojjati, MD, a rheumatologist and director of rheumatology operations at Loma Linda (Calif.) University Health. Dr. Hojjati was not affiliated with the study.

While the single-treatment therapy is promising, transfused T cells do carry risks. Some of the patients in the study experienced fever and muscle pain following the procedure, the authors noted. Dr. Belmont said more serious risks for this kind of therapy may include organ injury.

“This treatment can [also] increase incidence, for example, of pneumonia or shingles,” he said.

The study authors initially documented their work in a correspondence published in August 2021 in the New England Journal of Medicine. At that time, they reported that a 20-year-old woman with a severe refractory SLE went into remission following the treatment.

The five patients in the current study – four women and one man – were aged 18-24 years. All of the patients had previously been treated with several immunosuppressive medications, the study authors noted.

“This is an exciting approach, but many more patients need to be treated to really understand the efficacy and safety,” Dr. Belmont said.

Experts, including Dr. Belmont, also said the procedure is also costly and requires access to labs that can engineer a patient’s own T cells after they’ve been donated.

“The entire process must maintain sterility to avoid contamination, which would be harmful when reinfused into the patient,” he said.

According to Arthur Kavanaugh, MD, professor of medicine at UC San Diego Health, this form of therapy may be an option for severe refractory patients who have not responded well to other more established therapies.

“[It’s] exciting data, but very intense and so not likely to be something for an average patient in the near future,” said Dr. Kavanaugh, who was not affiliated with the study.

The study authors say they intend to create a larger trial to further explore which type of patient may benefit the most from this treatment, and for how long.

The study was supported by the German Research Foundation, the German Federal Ministry of Education and Research, the European Union, and the Innovative Medicines Initiative–funded project, Rheuma Tolerance for Cure. The study received no commercial funding, and the authors said they had no competing interests related to the study. None of the experts interviewed reported relevant financial relationships.

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

The patient’s history and examination are consistent with a diagnosis of pyogenic granuloma. Specifically, the history of rapid growth, friable nature, associated bleeding, and hemorrhagic crusting point to pyogenic granuloma as the most likely diagnosis.

Pyogenic granuloma is an acquired benign vascular growth of the skin or mucous membranes.¹ It most frequently occurs in children and young adults and most commonly affects the skin of the head, trunk, and extremities.² Common mucosal sites include the gingiva, lips, and tongue.² The etiology of pyogenic granuloma is unknown, though it is thought to be a process akin to the overgrowth of granulation tissue.^3,4 Expression of angiogenic factors and subsequent vascular hyperplasia are also implicated as key players in the pathogenesis of pyogenic granuloma.^1,4 In addition, several associated factors and inciting triggers have been proposed including trauma, infections, and hormonal fluctuations.^3-5 However, the majority of patients do not report predisposing factors or a history of prior trauma at the site.^3,6

Clinically, pyogenic granuloma usually presents as a painless, erythematous, dome-shaped friable papule or nodule that easily bleeds and may ulcerate. It typically undergoes a period of growth over weeks to months followed by stabilization. Occasionally, pyogenic granulomas will spontaneously involute, though most do not.⁷ Pyogenic granuloma may occur within an existing capillary malformation, such as a port wine stain, spontaneously or as a sequela of laser treatment.^8,9 Diagnosis of pyogenic granuloma can typically be made clinically on the basis of history and exam. Dermoscopic evaluation of pyogenic granuloma will reveal a homogeneous papule with a surrounding white-brown collarette, and potentially white intersecting lines.¹⁰ Histopathologic evaluation may be necessary to differentiate lesions from conditions that may mimic pyogenic granuloma.
 

What’s on the differential?

The differential diagnosis for pyogenic granuloma consists of Spitz nevus, cherry hemangioma, amelanotic melanoma, and glomus tumor.

Spitz nevus

Spitz nevus (spindle and epithelial cell nevus) is a benign melanocytic lesion that classically appears as a sharply circumscribed, smooth, dome-shaped, pink-red, or brown papule or plaque. There is typically a history of rapid growth over several months followed by stabilization. It usually presents in childhood or adolescence and is most commonly located on the face and extremities. While there are similarities in the appearance of Spitz nevi and pyogenic granuloma, Spitz nevi are not usually friable nor associated with bleeding as in our patient. Furthermore, on dermoscopy, Spitz nevus typically exhibits a starburst pattern with regularly distributed dotted vessels, or a peripheral globular pattern with reticular depigmentation. The definitive diagnosis of Spitz nevi relies on histopathologic evaluation, which is critical for discriminating Spitz nevi from melanoma.

Cherry hemangioma

Cherry angiomas are the most common type of acquired benign vascular proliferation. They present as small, bright red or violaceous macules or papules. However, they typically appear in early to midadulthood and increase in number with age. The age of our patient and solitary presentation of the lesion make this diagnosis unlikely. In addition, cherry angiomas are not usually associated with bleeding. It is important to note that, depending on the age of the patient, pyogenic granuloma may also be confused with infantile hemangioma. Infantile hemangiomas may become bright red papules, nodules, or plaques that appear in early infancy. They characteristically involute, which does not typically happen with pyogenic granuloma.

Amelanotic melanoma

Amelanotic melanoma is an uncommon variant of melanoma with little to no pigmentation. It may appear as a skin-colored to light-brown, pink, or red macule, papule, or nodule. The lesion may be asymmetric with irregular and well-defined borders. The variable and uncharacteristic appearance of this melanoma variant makes it diagnostically challenging and it is often confused with benign lesions including pyogenic granuloma. Dermoscopy can help distinguish amelanotic melanoma from other benign conditions, and will reveal areas of pink to white, polymorphous vessels and crystalline structures. However, ultimately biopsy and histopathological evaluation is necessary for accurate diagnosis.

Glomus tumor

Glomus tumors are rare, benign neoplasms originating from cells of the glomus body that presents as a red-purple, vascular papule or nodule. They are usually found in areas rich in glomus bodies, such as the subungual regions, fingertips, palms, wrists, and forearms. Glomus tumors are typically associated with tenderness, paroxysmal pain, and cold sensitivity. They do not bleed or ulcerate. While pyogenic granuloma may be confused for glomus tumor when present on the fingers or extremities, the location of the lesion in our patient is not consistent with a diagnosis of glomus tumor.

Management and disease course

Management with procedural or topical interventions is usually pursued for pyogenic granuloma because of frequent bleeding and ulceration of lesions. The most common approach is simple excision by a scoop or shave technique, with or without curettage and most commonly with electrocautery of the base. Other options include full-thickness excision, destruction with laser therapy, cryotherapy, or topical treatments (for example, timolol).¹¹ Lesion recurrence can occur with both surgical and nonsurgical management.¹¹ Regardless of management technique, it is useful to obtain histopathologic evaluation of tissue for accurate diagnosis.

Our patient underwent surgical destruction of her lower-lip lesion with shave excision followed by electrocautery. The surgical specimen was sent for pathology, which confirmed the diagnosis of pyogenic granuloma. The patient experienced no complications from the procedure and did not have recurrence of the lesion.
 

Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Ms. Sui nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Lin RL and Janniger CK. Cutis. 2004 Oct;74(4):229-33.

2. Harris MN et al. J Am Acad Dermatol. 2000 Jun;42(6):1012-6.

3. Pagliai KA and Cohen BA. Pediatr Dermatol. 2004 Jan-Feb;21(1):10-3.

4. Kamal R et al. J Oral Maxillofac Pathol. 2012 Jan;16(1):79-82.

5. Requena L and Sangueza OP. J Am Acad Dermatol. 1997 Dec;37(6):887-919.

6. Patrice SJ et al. Pediatr Dermatol. 1991 Dec;8(4):267-76.

7. Luba MC et al. Am Fam Physician. 2003 Feb 15;67(4):729-38.

8. Swerlick RA and Cooper PH. J Am Acad Dermatol. 1983 May;8(5):627-30.

9. Sheehan DJ and Lesher JL Jr. Cutis. 2004 Mar;73(3):175-80.

10. Zaballos P et al. Br J Dermatol. 2006 Jun;154(6):1108-11.

11. Lee J et al. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1216-20. .

The patient’s history and examination are consistent with a diagnosis of pyogenic granuloma. Specifically, the history of rapid growth, friable nature, associated bleeding, and hemorrhagic crusting point to pyogenic granuloma as the most likely diagnosis.

Pyogenic granuloma is an acquired benign vascular growth of the skin or mucous membranes.¹ It most frequently occurs in children and young adults and most commonly affects the skin of the head, trunk, and extremities.² Common mucosal sites include the gingiva, lips, and tongue.² The etiology of pyogenic granuloma is unknown, though it is thought to be a process akin to the overgrowth of granulation tissue.^3,4 Expression of angiogenic factors and subsequent vascular hyperplasia are also implicated as key players in the pathogenesis of pyogenic granuloma.^1,4 In addition, several associated factors and inciting triggers have been proposed including trauma, infections, and hormonal fluctuations.^3-5 However, the majority of patients do not report predisposing factors or a history of prior trauma at the site.^3,6

Clinically, pyogenic granuloma usually presents as a painless, erythematous, dome-shaped friable papule or nodule that easily bleeds and may ulcerate. It typically undergoes a period of growth over weeks to months followed by stabilization. Occasionally, pyogenic granulomas will spontaneously involute, though most do not.⁷ Pyogenic granuloma may occur within an existing capillary malformation, such as a port wine stain, spontaneously or as a sequela of laser treatment.^8,9 Diagnosis of pyogenic granuloma can typically be made clinically on the basis of history and exam. Dermoscopic evaluation of pyogenic granuloma will reveal a homogeneous papule with a surrounding white-brown collarette, and potentially white intersecting lines.¹⁰ Histopathologic evaluation may be necessary to differentiate lesions from conditions that may mimic pyogenic granuloma.
 

What’s on the differential?

The differential diagnosis for pyogenic granuloma consists of Spitz nevus, cherry hemangioma, amelanotic melanoma, and glomus tumor.

Spitz nevus

Spitz nevus (spindle and epithelial cell nevus) is a benign melanocytic lesion that classically appears as a sharply circumscribed, smooth, dome-shaped, pink-red, or brown papule or plaque. There is typically a history of rapid growth over several months followed by stabilization. It usually presents in childhood or adolescence and is most commonly located on the face and extremities. While there are similarities in the appearance of Spitz nevi and pyogenic granuloma, Spitz nevi are not usually friable nor associated with bleeding as in our patient. Furthermore, on dermoscopy, Spitz nevus typically exhibits a starburst pattern with regularly distributed dotted vessels, or a peripheral globular pattern with reticular depigmentation. The definitive diagnosis of Spitz nevi relies on histopathologic evaluation, which is critical for discriminating Spitz nevi from melanoma.

Cherry hemangioma

Cherry angiomas are the most common type of acquired benign vascular proliferation. They present as small, bright red or violaceous macules or papules. However, they typically appear in early to midadulthood and increase in number with age. The age of our patient and solitary presentation of the lesion make this diagnosis unlikely. In addition, cherry angiomas are not usually associated with bleeding. It is important to note that, depending on the age of the patient, pyogenic granuloma may also be confused with infantile hemangioma. Infantile hemangiomas may become bright red papules, nodules, or plaques that appear in early infancy. They characteristically involute, which does not typically happen with pyogenic granuloma.

Amelanotic melanoma

Amelanotic melanoma is an uncommon variant of melanoma with little to no pigmentation. It may appear as a skin-colored to light-brown, pink, or red macule, papule, or nodule. The lesion may be asymmetric with irregular and well-defined borders. The variable and uncharacteristic appearance of this melanoma variant makes it diagnostically challenging and it is often confused with benign lesions including pyogenic granuloma. Dermoscopy can help distinguish amelanotic melanoma from other benign conditions, and will reveal areas of pink to white, polymorphous vessels and crystalline structures. However, ultimately biopsy and histopathological evaluation is necessary for accurate diagnosis.

Glomus tumor

Glomus tumors are rare, benign neoplasms originating from cells of the glomus body that presents as a red-purple, vascular papule or nodule. They are usually found in areas rich in glomus bodies, such as the subungual regions, fingertips, palms, wrists, and forearms. Glomus tumors are typically associated with tenderness, paroxysmal pain, and cold sensitivity. They do not bleed or ulcerate. While pyogenic granuloma may be confused for glomus tumor when present on the fingers or extremities, the location of the lesion in our patient is not consistent with a diagnosis of glomus tumor.

Management and disease course

Management with procedural or topical interventions is usually pursued for pyogenic granuloma because of frequent bleeding and ulceration of lesions. The most common approach is simple excision by a scoop or shave technique, with or without curettage and most commonly with electrocautery of the base. Other options include full-thickness excision, destruction with laser therapy, cryotherapy, or topical treatments (for example, timolol).¹¹ Lesion recurrence can occur with both surgical and nonsurgical management.¹¹ Regardless of management technique, it is useful to obtain histopathologic evaluation of tissue for accurate diagnosis.

Our patient underwent surgical destruction of her lower-lip lesion with shave excision followed by electrocautery. The surgical specimen was sent for pathology, which confirmed the diagnosis of pyogenic granuloma. The patient experienced no complications from the procedure and did not have recurrence of the lesion.
 

Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Ms. Sui nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Lin RL and Janniger CK. Cutis. 2004 Oct;74(4):229-33.

2. Harris MN et al. J Am Acad Dermatol. 2000 Jun;42(6):1012-6.

3. Pagliai KA and Cohen BA. Pediatr Dermatol. 2004 Jan-Feb;21(1):10-3.

4. Kamal R et al. J Oral Maxillofac Pathol. 2012 Jan;16(1):79-82.

5. Requena L and Sangueza OP. J Am Acad Dermatol. 1997 Dec;37(6):887-919.

6. Patrice SJ et al. Pediatr Dermatol. 1991 Dec;8(4):267-76.

7. Luba MC et al. Am Fam Physician. 2003 Feb 15;67(4):729-38.

8. Swerlick RA and Cooper PH. J Am Acad Dermatol. 1983 May;8(5):627-30.

9. Sheehan DJ and Lesher JL Jr. Cutis. 2004 Mar;73(3):175-80.

10. Zaballos P et al. Br J Dermatol. 2006 Jun;154(6):1108-11.

11. Lee J et al. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1216-20. .

The patient’s history and examination are consistent with a diagnosis of pyogenic granuloma. Specifically, the history of rapid growth, friable nature, associated bleeding, and hemorrhagic crusting point to pyogenic granuloma as the most likely diagnosis.

Pyogenic granuloma is an acquired benign vascular growth of the skin or mucous membranes.¹ It most frequently occurs in children and young adults and most commonly affects the skin of the head, trunk, and extremities.² Common mucosal sites include the gingiva, lips, and tongue.² The etiology of pyogenic granuloma is unknown, though it is thought to be a process akin to the overgrowth of granulation tissue.^3,4 Expression of angiogenic factors and subsequent vascular hyperplasia are also implicated as key players in the pathogenesis of pyogenic granuloma.^1,4 In addition, several associated factors and inciting triggers have been proposed including trauma, infections, and hormonal fluctuations.^3-5 However, the majority of patients do not report predisposing factors or a history of prior trauma at the site.^3,6

Clinically, pyogenic granuloma usually presents as a painless, erythematous, dome-shaped friable papule or nodule that easily bleeds and may ulcerate. It typically undergoes a period of growth over weeks to months followed by stabilization. Occasionally, pyogenic granulomas will spontaneously involute, though most do not.⁷ Pyogenic granuloma may occur within an existing capillary malformation, such as a port wine stain, spontaneously or as a sequela of laser treatment.^8,9 Diagnosis of pyogenic granuloma can typically be made clinically on the basis of history and exam. Dermoscopic evaluation of pyogenic granuloma will reveal a homogeneous papule with a surrounding white-brown collarette, and potentially white intersecting lines.¹⁰ Histopathologic evaluation may be necessary to differentiate lesions from conditions that may mimic pyogenic granuloma.
 

What’s on the differential?

The differential diagnosis for pyogenic granuloma consists of Spitz nevus, cherry hemangioma, amelanotic melanoma, and glomus tumor.

Spitz nevus

Spitz nevus (spindle and epithelial cell nevus) is a benign melanocytic lesion that classically appears as a sharply circumscribed, smooth, dome-shaped, pink-red, or brown papule or plaque. There is typically a history of rapid growth over several months followed by stabilization. It usually presents in childhood or adolescence and is most commonly located on the face and extremities. While there are similarities in the appearance of Spitz nevi and pyogenic granuloma, Spitz nevi are not usually friable nor associated with bleeding as in our patient. Furthermore, on dermoscopy, Spitz nevus typically exhibits a starburst pattern with regularly distributed dotted vessels, or a peripheral globular pattern with reticular depigmentation. The definitive diagnosis of Spitz nevi relies on histopathologic evaluation, which is critical for discriminating Spitz nevi from melanoma.

Cherry hemangioma

Cherry angiomas are the most common type of acquired benign vascular proliferation. They present as small, bright red or violaceous macules or papules. However, they typically appear in early to midadulthood and increase in number with age. The age of our patient and solitary presentation of the lesion make this diagnosis unlikely. In addition, cherry angiomas are not usually associated with bleeding. It is important to note that, depending on the age of the patient, pyogenic granuloma may also be confused with infantile hemangioma. Infantile hemangiomas may become bright red papules, nodules, or plaques that appear in early infancy. They characteristically involute, which does not typically happen with pyogenic granuloma.

Amelanotic melanoma

Amelanotic melanoma is an uncommon variant of melanoma with little to no pigmentation. It may appear as a skin-colored to light-brown, pink, or red macule, papule, or nodule. The lesion may be asymmetric with irregular and well-defined borders. The variable and uncharacteristic appearance of this melanoma variant makes it diagnostically challenging and it is often confused with benign lesions including pyogenic granuloma. Dermoscopy can help distinguish amelanotic melanoma from other benign conditions, and will reveal areas of pink to white, polymorphous vessels and crystalline structures. However, ultimately biopsy and histopathological evaluation is necessary for accurate diagnosis.

Glomus tumor

Glomus tumors are rare, benign neoplasms originating from cells of the glomus body that presents as a red-purple, vascular papule or nodule. They are usually found in areas rich in glomus bodies, such as the subungual regions, fingertips, palms, wrists, and forearms. Glomus tumors are typically associated with tenderness, paroxysmal pain, and cold sensitivity. They do not bleed or ulcerate. While pyogenic granuloma may be confused for glomus tumor when present on the fingers or extremities, the location of the lesion in our patient is not consistent with a diagnosis of glomus tumor.

Management and disease course

Management with procedural or topical interventions is usually pursued for pyogenic granuloma because of frequent bleeding and ulceration of lesions. The most common approach is simple excision by a scoop or shave technique, with or without curettage and most commonly with electrocautery of the base. Other options include full-thickness excision, destruction with laser therapy, cryotherapy, or topical treatments (for example, timolol).¹¹ Lesion recurrence can occur with both surgical and nonsurgical management.¹¹ Regardless of management technique, it is useful to obtain histopathologic evaluation of tissue for accurate diagnosis.

Our patient underwent surgical destruction of her lower-lip lesion with shave excision followed by electrocautery. The surgical specimen was sent for pathology, which confirmed the diagnosis of pyogenic granuloma. The patient experienced no complications from the procedure and did not have recurrence of the lesion.
 

Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Ms. Sui nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Lin RL and Janniger CK. Cutis. 2004 Oct;74(4):229-33.

2. Harris MN et al. J Am Acad Dermatol. 2000 Jun;42(6):1012-6.

3. Pagliai KA and Cohen BA. Pediatr Dermatol. 2004 Jan-Feb;21(1):10-3.

4. Kamal R et al. J Oral Maxillofac Pathol. 2012 Jan;16(1):79-82.

5. Requena L and Sangueza OP. J Am Acad Dermatol. 1997 Dec;37(6):887-919.

6. Patrice SJ et al. Pediatr Dermatol. 1991 Dec;8(4):267-76.

7. Luba MC et al. Am Fam Physician. 2003 Feb 15;67(4):729-38.

8. Swerlick RA and Cooper PH. J Am Acad Dermatol. 1983 May;8(5):627-30.

9. Sheehan DJ and Lesher JL Jr. Cutis. 2004 Mar;73(3):175-80.

10. Zaballos P et al. Br J Dermatol. 2006 Jun;154(6):1108-11.

11. Lee J et al. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1216-20. .

Metabolism a player in circadian rhythm section

Are you an early bird, or do you wake up and stare at your phone, wondering why you were up watching “The Crown” until 3 a.m.? Recent research suggests that people who wake up earlier tend to be more active during the day and burn more fat than those who sleep in. Fat builds up in the night owls, putting them at higher risk of type 2 diabetes and heart disease.

The study gives physicians something to think about when assessing a patient’s risk factors. “This could help medical professionals consider another behavioral factor contributing to disease risk,” Steven Malin, PhD, lead author of the study and expert in metabolism at Rutgers University in New Brunswick, N.J., said in The Guardian.

Geber86/E+

For the research, 51 participants were divided into night owls and early birds, depending on their answers to a questionnaire. They were examined, monitored for a week, and assessed while doing various activities. Those who woke up early tended to be more sensitive to insulin and burned off fat faster than those who woke up late, the researchers explained.

“Night owls are reported to have a higher risk of obesity, type 2 diabetes, and cardiovascular disease when compared with early birds,” Dr. Malin said. “A potential explanation is they become misaligned with their circadian rhythm for various reasons, but most notably among adults would be work.”

We all know that we may not be at our best when we throw off our internal clocks by going to sleep late and waking up early. Think about that next time you start another episode on Netflix at 2:57 a.m.
 

Mosquitoes, chemical cocktails, and glass sock beads

We all know that mosquitoes are annoying little disease vectors with a taste for human blood. One of the less-known things about mosquitoes is what attracts them to humans in the first place. It’s so less known that, until now, it was unknown. Oh sure, we knew that odor was involved, and that lactic acid was part of the odor equation, but what are the specific chemicals? Well, there’s carbon dioxide … and ammonia. Those were already known.

Ring Cardé, PhD, an entomologist at the University of California, Riverside, wasn’t convinced. “I suspected there was something undiscovered about the chemistry of odors luring the yellow fever mosquito. I wanted to nail down the exact blend,” he said in a statement from the university.

Dr. Cardé and his associates eventually figured out that the exact chemical cocktail attracting female Aedes aegypti mosquitoes was a combination of carbon dioxide plus two chemicals, 2-ketoglutaric acid and lactic acid. The odor from these chemicals enables mosquitoes to locate and land on their victim and “also encourages probing, the use of piercing mouthparts to find blood,” the university said.

This amazing destination of science is important, but we have to acknowledge the journey as well. To do that we turn to one of Dr. Cardé’s associates, Jan Bello, PhD, formerly of Cal-Riverside and now with insect pest control company Provivi. Turns out that 2-ketoglutaric acid is tricky stuff because the methods typically used to identify chemicals don’t work on it.

Dr. Bello employed a somewhat unorthodox chemical extraction method: He filled his socks with glass beads and walked around with the beads in his socks.

Jan Bello/UCR

“Wearing the beads felt almost like a massage, like squeezing stress balls full of sand, but with your feet,” Dr. Bello said. “The most frustrating part of doing it for a long time is that they would get stuck in between your toes, so it would be uncomfortable after a while.”

We hate when science gets stuck between our toes, but we love it when scientists write their own punchlines.
 

The MS drugs are better down where it’s wetter, take it from me

The myth of the mermaid is one with hundreds, if not thousands, of years of history. The ancient Greeks had the mythological siren, while the Babylonians depicted kulullû (which were mermen – never let the Babylonians be known as noninclusive) in artwork as far back as 1600 BC. Cultures as far flung as Japan, southern Africa, and New Zealand have folkloric figures similar to the mermaid. It is most decidedly not a creation of western Europe, Hans Christian Andersen, or Disney.

AG Kostenis-Gomeza / University of Bonn

With that mild rant out of the way, let’s move to Germany and a group of researchers from the University of Bonn, who have not created a mermaid. They did, however, add human genes to a zebrafish for research purposes, which feels uncomfortably close. Nothing better than unholy animal-human hybrids, right?

Stick with us here, because the researchers did have a good reason for their gene splicing. Zebrafish and humans both have the GPR17 receptor, which is highly active in nerve tissue. When GPR17 is overactivated, diseases such as multiple sclerosis can develop. Because the zebrafish has this receptor, which performs the same function in its body as in ours, it’s a prime candidate for replacement. Also, zebrafish larvae are transparent, which makes it very easy to observe a drug working.

That said, fish and humans are very far apart, genetically speaking. Big shock right there. But by replacing their GPR17 receptor with ours, the scientists have created a fish that we could test drug candidates on and be assured that they would also work on humans. Actually testing drugs for MS on these humanized zebrafish was beyond the scope of the study, but the researchers said that the new genes function normally in the fish larvae, making them a promising new avenue for MS drug development.

Can we all promise not to tell Disney that human DNA can be spliced into a fish without consequence? Otherwise, we’re just going to have to sit through another “Little Mermaid” adaptation in 30 years, this one in super live-action featuring actual, real-life mermaids. And we’re not ready for that level of man-made horror just yet.
 

Beware of the fly vomit

Picture this: You’re outside at a picnic or barbecue, loading a plate with food. In a brief moment of conversation a fly lands right on top of your sandwich. You shoo it away and think nothing more of it, eating the sandwich anyway. We’ve all been there.

A recent study is making us think again.

John Stoffolano, an entomology professor at the University of Massachusetts, Amherst, claims that too much attention has been focused on pathogen transmission by the biting, blood-feeding flies when really we should be taking note of the nonbiting, or synanthropic, flies we live with, which may have a greater impact on the transmission of pathogens right in our own homes.

arian.suresh/PxHere

Metabolism a player in circadian rhythm section

Are you an early bird, or do you wake up and stare at your phone, wondering why you were up watching “The Crown” until 3 a.m.? Recent research suggests that people who wake up earlier tend to be more active during the day and burn more fat than those who sleep in. Fat builds up in the night owls, putting them at higher risk of type 2 diabetes and heart disease.

The study gives physicians something to think about when assessing a patient’s risk factors. “This could help medical professionals consider another behavioral factor contributing to disease risk,” Steven Malin, PhD, lead author of the study and expert in metabolism at Rutgers University in New Brunswick, N.J., said in The Guardian.

Geber86/E+

For the research, 51 participants were divided into night owls and early birds, depending on their answers to a questionnaire. They were examined, monitored for a week, and assessed while doing various activities. Those who woke up early tended to be more sensitive to insulin and burned off fat faster than those who woke up late, the researchers explained.

“Night owls are reported to have a higher risk of obesity, type 2 diabetes, and cardiovascular disease when compared with early birds,” Dr. Malin said. “A potential explanation is they become misaligned with their circadian rhythm for various reasons, but most notably among adults would be work.”

We all know that we may not be at our best when we throw off our internal clocks by going to sleep late and waking up early. Think about that next time you start another episode on Netflix at 2:57 a.m.
 

Mosquitoes, chemical cocktails, and glass sock beads

We all know that mosquitoes are annoying little disease vectors with a taste for human blood. One of the less-known things about mosquitoes is what attracts them to humans in the first place. It’s so less known that, until now, it was unknown. Oh sure, we knew that odor was involved, and that lactic acid was part of the odor equation, but what are the specific chemicals? Well, there’s carbon dioxide … and ammonia. Those were already known.

Ring Cardé, PhD, an entomologist at the University of California, Riverside, wasn’t convinced. “I suspected there was something undiscovered about the chemistry of odors luring the yellow fever mosquito. I wanted to nail down the exact blend,” he said in a statement from the university.

Dr. Cardé and his associates eventually figured out that the exact chemical cocktail attracting female Aedes aegypti mosquitoes was a combination of carbon dioxide plus two chemicals, 2-ketoglutaric acid and lactic acid. The odor from these chemicals enables mosquitoes to locate and land on their victim and “also encourages probing, the use of piercing mouthparts to find blood,” the university said.

This amazing destination of science is important, but we have to acknowledge the journey as well. To do that we turn to one of Dr. Cardé’s associates, Jan Bello, PhD, formerly of Cal-Riverside and now with insect pest control company Provivi. Turns out that 2-ketoglutaric acid is tricky stuff because the methods typically used to identify chemicals don’t work on it.

Dr. Bello employed a somewhat unorthodox chemical extraction method: He filled his socks with glass beads and walked around with the beads in his socks.

Jan Bello/UCR

“Wearing the beads felt almost like a massage, like squeezing stress balls full of sand, but with your feet,” Dr. Bello said. “The most frustrating part of doing it for a long time is that they would get stuck in between your toes, so it would be uncomfortable after a while.”

We hate when science gets stuck between our toes, but we love it when scientists write their own punchlines.
 

The MS drugs are better down where it’s wetter, take it from me

The myth of the mermaid is one with hundreds, if not thousands, of years of history. The ancient Greeks had the mythological siren, while the Babylonians depicted kulullû (which were mermen – never let the Babylonians be known as noninclusive) in artwork as far back as 1600 BC. Cultures as far flung as Japan, southern Africa, and New Zealand have folkloric figures similar to the mermaid. It is most decidedly not a creation of western Europe, Hans Christian Andersen, or Disney.

AG Kostenis-Gomeza / University of Bonn

With that mild rant out of the way, let’s move to Germany and a group of researchers from the University of Bonn, who have not created a mermaid. They did, however, add human genes to a zebrafish for research purposes, which feels uncomfortably close. Nothing better than unholy animal-human hybrids, right?

Stick with us here, because the researchers did have a good reason for their gene splicing. Zebrafish and humans both have the GPR17 receptor, which is highly active in nerve tissue. When GPR17 is overactivated, diseases such as multiple sclerosis can develop. Because the zebrafish has this receptor, which performs the same function in its body as in ours, it’s a prime candidate for replacement. Also, zebrafish larvae are transparent, which makes it very easy to observe a drug working.

That said, fish and humans are very far apart, genetically speaking. Big shock right there. But by replacing their GPR17 receptor with ours, the scientists have created a fish that we could test drug candidates on and be assured that they would also work on humans. Actually testing drugs for MS on these humanized zebrafish was beyond the scope of the study, but the researchers said that the new genes function normally in the fish larvae, making them a promising new avenue for MS drug development.

Can we all promise not to tell Disney that human DNA can be spliced into a fish without consequence? Otherwise, we’re just going to have to sit through another “Little Mermaid” adaptation in 30 years, this one in super live-action featuring actual, real-life mermaids. And we’re not ready for that level of man-made horror just yet.
 

Beware of the fly vomit

Picture this: You’re outside at a picnic or barbecue, loading a plate with food. In a brief moment of conversation a fly lands right on top of your sandwich. You shoo it away and think nothing more of it, eating the sandwich anyway. We’ve all been there.

A recent study is making us think again.

John Stoffolano, an entomology professor at the University of Massachusetts, Amherst, claims that too much attention has been focused on pathogen transmission by the biting, blood-feeding flies when really we should be taking note of the nonbiting, or synanthropic, flies we live with, which may have a greater impact on the transmission of pathogens right in our own homes.

arian.suresh/PxHere

Metabolism a player in circadian rhythm section

Are you an early bird, or do you wake up and stare at your phone, wondering why you were up watching “The Crown” until 3 a.m.? Recent research suggests that people who wake up earlier tend to be more active during the day and burn more fat than those who sleep in. Fat builds up in the night owls, putting them at higher risk of type 2 diabetes and heart disease.

The study gives physicians something to think about when assessing a patient’s risk factors. “This could help medical professionals consider another behavioral factor contributing to disease risk,” Steven Malin, PhD, lead author of the study and expert in metabolism at Rutgers University in New Brunswick, N.J., said in The Guardian.

Geber86/E+

For the research, 51 participants were divided into night owls and early birds, depending on their answers to a questionnaire. They were examined, monitored for a week, and assessed while doing various activities. Those who woke up early tended to be more sensitive to insulin and burned off fat faster than those who woke up late, the researchers explained.

“Night owls are reported to have a higher risk of obesity, type 2 diabetes, and cardiovascular disease when compared with early birds,” Dr. Malin said. “A potential explanation is they become misaligned with their circadian rhythm for various reasons, but most notably among adults would be work.”

We all know that we may not be at our best when we throw off our internal clocks by going to sleep late and waking up early. Think about that next time you start another episode on Netflix at 2:57 a.m.
 

Mosquitoes, chemical cocktails, and glass sock beads

We all know that mosquitoes are annoying little disease vectors with a taste for human blood. One of the less-known things about mosquitoes is what attracts them to humans in the first place. It’s so less known that, until now, it was unknown. Oh sure, we knew that odor was involved, and that lactic acid was part of the odor equation, but what are the specific chemicals? Well, there’s carbon dioxide … and ammonia. Those were already known.

Ring Cardé, PhD, an entomologist at the University of California, Riverside, wasn’t convinced. “I suspected there was something undiscovered about the chemistry of odors luring the yellow fever mosquito. I wanted to nail down the exact blend,” he said in a statement from the university.

Dr. Cardé and his associates eventually figured out that the exact chemical cocktail attracting female Aedes aegypti mosquitoes was a combination of carbon dioxide plus two chemicals, 2-ketoglutaric acid and lactic acid. The odor from these chemicals enables mosquitoes to locate and land on their victim and “also encourages probing, the use of piercing mouthparts to find blood,” the university said.

This amazing destination of science is important, but we have to acknowledge the journey as well. To do that we turn to one of Dr. Cardé’s associates, Jan Bello, PhD, formerly of Cal-Riverside and now with insect pest control company Provivi. Turns out that 2-ketoglutaric acid is tricky stuff because the methods typically used to identify chemicals don’t work on it.

Dr. Bello employed a somewhat unorthodox chemical extraction method: He filled his socks with glass beads and walked around with the beads in his socks.

Jan Bello/UCR

“Wearing the beads felt almost like a massage, like squeezing stress balls full of sand, but with your feet,” Dr. Bello said. “The most frustrating part of doing it for a long time is that they would get stuck in between your toes, so it would be uncomfortable after a while.”

We hate when science gets stuck between our toes, but we love it when scientists write their own punchlines.
 

The MS drugs are better down where it’s wetter, take it from me

The myth of the mermaid is one with hundreds, if not thousands, of years of history. The ancient Greeks had the mythological siren, while the Babylonians depicted kulullû (which were mermen – never let the Babylonians be known as noninclusive) in artwork as far back as 1600 BC. Cultures as far flung as Japan, southern Africa, and New Zealand have folkloric figures similar to the mermaid. It is most decidedly not a creation of western Europe, Hans Christian Andersen, or Disney.

AG Kostenis-Gomeza / University of Bonn

With that mild rant out of the way, let’s move to Germany and a group of researchers from the University of Bonn, who have not created a mermaid. They did, however, add human genes to a zebrafish for research purposes, which feels uncomfortably close. Nothing better than unholy animal-human hybrids, right?

Stick with us here, because the researchers did have a good reason for their gene splicing. Zebrafish and humans both have the GPR17 receptor, which is highly active in nerve tissue. When GPR17 is overactivated, diseases such as multiple sclerosis can develop. Because the zebrafish has this receptor, which performs the same function in its body as in ours, it’s a prime candidate for replacement. Also, zebrafish larvae are transparent, which makes it very easy to observe a drug working.

That said, fish and humans are very far apart, genetically speaking. Big shock right there. But by replacing their GPR17 receptor with ours, the scientists have created a fish that we could test drug candidates on and be assured that they would also work on humans. Actually testing drugs for MS on these humanized zebrafish was beyond the scope of the study, but the researchers said that the new genes function normally in the fish larvae, making them a promising new avenue for MS drug development.

Can we all promise not to tell Disney that human DNA can be spliced into a fish without consequence? Otherwise, we’re just going to have to sit through another “Little Mermaid” adaptation in 30 years, this one in super live-action featuring actual, real-life mermaids. And we’re not ready for that level of man-made horror just yet.
 

Beware of the fly vomit

Picture this: You’re outside at a picnic or barbecue, loading a plate with food. In a brief moment of conversation a fly lands right on top of your sandwich. You shoo it away and think nothing more of it, eating the sandwich anyway. We’ve all been there.

A recent study is making us think again.

John Stoffolano, an entomology professor at the University of Massachusetts, Amherst, claims that too much attention has been focused on pathogen transmission by the biting, blood-feeding flies when really we should be taking note of the nonbiting, or synanthropic, flies we live with, which may have a greater impact on the transmission of pathogens right in our own homes.

arian.suresh/PxHere

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

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

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

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

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

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

Apremilast (Otezla), an oral drug approved for adult psoriasis, appears to reduce psoriasis severity in some children with moderate to severe psoriasis not controlled by topical therapy, according to the results of a phase 3 trial.

“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.

“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
 

Key findings

Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.

At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).

A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
 

Results unaffected by weight and age

Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.

A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.

When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.

As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.

Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
 

Safety of apremilast in children

“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”

The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.

Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.

There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).

The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.

Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
 

Expect further data

Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.

The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.

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

Apremilast (Otezla), an oral drug approved for adult psoriasis, appears to reduce psoriasis severity in some children with moderate to severe psoriasis not controlled by topical therapy, according to the results of a phase 3 trial.

“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.

“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
 

Key findings

Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.

At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).

A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
 

Results unaffected by weight and age

Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.

A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.

When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.

As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.

Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
 

Safety of apremilast in children

“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”

The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.

Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.

There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).

The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.

Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
 

Expect further data

Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.

The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.

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

Apremilast (Otezla), an oral drug approved for adult psoriasis, appears to reduce psoriasis severity in some children with moderate to severe psoriasis not controlled by topical therapy, according to the results of a phase 3 trial.

“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.

“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
 

Key findings

Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.

At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).

A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
 

Results unaffected by weight and age

Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.

A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.

When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.

As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.

Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
 

Safety of apremilast in children

“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”

The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.

Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.

There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).

The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.

Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
 

Expect further data

Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.

The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.

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