Clinician Reviews

Adults with rosacea had a significantly higher prevalence of multiple risk factors for cardiometabolic disease, according to the results of a meta-analysis of more than 50,000 patients.

To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.

In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.

Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.

Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
 

Findings don’t show causality

The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”

However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.

“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.

“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”

Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”

“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.

The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.

SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.

Adults with rosacea had a significantly higher prevalence of multiple risk factors for cardiometabolic disease, according to the results of a meta-analysis of more than 50,000 patients.

To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.

In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.

Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.

Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
 

Findings don’t show causality

The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”

However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.

“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.

“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”

Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”

“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.

The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.

SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.

Adults with rosacea had a significantly higher prevalence of multiple risk factors for cardiometabolic disease, according to the results of a meta-analysis of more than 50,000 patients.

To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.

In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.

Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.

Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
 

Findings don’t show causality

The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”

However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.

“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.

“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”

Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”

“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.

The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.

SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.

The Diagnosis: Warty Dyskeratoma 

Warty dyskeratoma (WD) is a benign cutaneous tumor that was first described in 1954 as isolated Darier disease (DD). In 1957, Szymanski¹ renamed it warty dyskeratoma as a distinct condition from DD. Warty dyskeratoma typically presents as a flesh-colored to brownish, round, well-demarcated, and slightly elevated papule or nodule accompanied by an umbilical invagination at the center. It most commonly arises on the scalp, face, or neck.² In contrast to DD, familial occurrence is uncommon. It usually is difficult to distinguish WD from other conditions such as seborrheic keratosis, verruca vulgaris, or keratoacanthoma due to its macroscopic features. Therefore, histopathologic investigation is necessary for a precise diagnosis. 

In our case, histologic investigation revealed a symmetric cup-shaped invagination filled with acantholytic and dyskeratotic keratinocytes with no atypia or mitotic figures (Figure, A). The bottom of the invagination was occupied with numerous villi covered by a single layer of basal cells (Figure, B). At the edge of the invagination, corps ronds and grains were observed in the granular and cornified layers, respectively (Figure, C).

The hallmark histopathologic findings are acantholysis and dyskeratosis just above the basal cell layer, called focal acantholytic dyskeratosis. The differential diagnosis includes other disorders associated with focal acantholytic dyskeratosis, such as DD and acantholytic squamous cell carcinoma.³ Distinguishing WD from DD may be difficult in rare cases with multiple lesions.⁴ In such cases, an autosomal-dominant inheritance pattern and younger age of onset should prompt clinicians to seek for mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2, for the diagnosis of DD.⁵ Additionally, the presence of atypia or mitotic figures will rule out malignant disorders such as squamous cell carcinoma.  

Although the pathogenesis of WD is not fully understood, most clinicians consider it a follicular adnexal neoplasm because the lesions often are connected to the pilosebaceous unit on microscopic observation.⁶ Although WD-like lesions arising from the oral mucosa have been reported,⁷ their etiology may be different from WD because the oral mucosa lacks hair follicles.⁸ The term warty leads to speculation of the contribution of human papillomavirus to the pathogenesis of WD, but this has been questioned due to the negative result of viral DNA detection from WD lesions by polymerase chain reaction analysis.² Therefore, the term follicular dyskeratoma has been suggested as a novel denomination that reflects its etiology more precisely.²  

The efficacy of topical treatment has not yet been established. Cryosurgery is another therapeutic option, but it sometimes fails.⁹ As performed in our patient, excisional biopsy is the most reasonable treatment option to obtain both complete removal and precise diagnosis.  
 

The Diagnosis: Warty Dyskeratoma 

Warty dyskeratoma (WD) is a benign cutaneous tumor that was first described in 1954 as isolated Darier disease (DD). In 1957, Szymanski¹ renamed it warty dyskeratoma as a distinct condition from DD. Warty dyskeratoma typically presents as a flesh-colored to brownish, round, well-demarcated, and slightly elevated papule or nodule accompanied by an umbilical invagination at the center. It most commonly arises on the scalp, face, or neck.² In contrast to DD, familial occurrence is uncommon. It usually is difficult to distinguish WD from other conditions such as seborrheic keratosis, verruca vulgaris, or keratoacanthoma due to its macroscopic features. Therefore, histopathologic investigation is necessary for a precise diagnosis. 

In our case, histologic investigation revealed a symmetric cup-shaped invagination filled with acantholytic and dyskeratotic keratinocytes with no atypia or mitotic figures (Figure, A). The bottom of the invagination was occupied with numerous villi covered by a single layer of basal cells (Figure, B). At the edge of the invagination, corps ronds and grains were observed in the granular and cornified layers, respectively (Figure, C).

The hallmark histopathologic findings are acantholysis and dyskeratosis just above the basal cell layer, called focal acantholytic dyskeratosis. The differential diagnosis includes other disorders associated with focal acantholytic dyskeratosis, such as DD and acantholytic squamous cell carcinoma.³ Distinguishing WD from DD may be difficult in rare cases with multiple lesions.⁴ In such cases, an autosomal-dominant inheritance pattern and younger age of onset should prompt clinicians to seek for mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2, for the diagnosis of DD.⁵ Additionally, the presence of atypia or mitotic figures will rule out malignant disorders such as squamous cell carcinoma.  

Although the pathogenesis of WD is not fully understood, most clinicians consider it a follicular adnexal neoplasm because the lesions often are connected to the pilosebaceous unit on microscopic observation.⁶ Although WD-like lesions arising from the oral mucosa have been reported,⁷ their etiology may be different from WD because the oral mucosa lacks hair follicles.⁸ The term warty leads to speculation of the contribution of human papillomavirus to the pathogenesis of WD, but this has been questioned due to the negative result of viral DNA detection from WD lesions by polymerase chain reaction analysis.² Therefore, the term follicular dyskeratoma has been suggested as a novel denomination that reflects its etiology more precisely.²  

The efficacy of topical treatment has not yet been established. Cryosurgery is another therapeutic option, but it sometimes fails.⁹ As performed in our patient, excisional biopsy is the most reasonable treatment option to obtain both complete removal and precise diagnosis.  
 

The Diagnosis: Warty Dyskeratoma 

Warty dyskeratoma (WD) is a benign cutaneous tumor that was first described in 1954 as isolated Darier disease (DD). In 1957, Szymanski¹ renamed it warty dyskeratoma as a distinct condition from DD. Warty dyskeratoma typically presents as a flesh-colored to brownish, round, well-demarcated, and slightly elevated papule or nodule accompanied by an umbilical invagination at the center. It most commonly arises on the scalp, face, or neck.² In contrast to DD, familial occurrence is uncommon. It usually is difficult to distinguish WD from other conditions such as seborrheic keratosis, verruca vulgaris, or keratoacanthoma due to its macroscopic features. Therefore, histopathologic investigation is necessary for a precise diagnosis. 

In our case, histologic investigation revealed a symmetric cup-shaped invagination filled with acantholytic and dyskeratotic keratinocytes with no atypia or mitotic figures (Figure, A). The bottom of the invagination was occupied with numerous villi covered by a single layer of basal cells (Figure, B). At the edge of the invagination, corps ronds and grains were observed in the granular and cornified layers, respectively (Figure, C).

The hallmark histopathologic findings are acantholysis and dyskeratosis just above the basal cell layer, called focal acantholytic dyskeratosis. The differential diagnosis includes other disorders associated with focal acantholytic dyskeratosis, such as DD and acantholytic squamous cell carcinoma.³ Distinguishing WD from DD may be difficult in rare cases with multiple lesions.⁴ In such cases, an autosomal-dominant inheritance pattern and younger age of onset should prompt clinicians to seek for mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2, for the diagnosis of DD.⁵ Additionally, the presence of atypia or mitotic figures will rule out malignant disorders such as squamous cell carcinoma.  

Although the pathogenesis of WD is not fully understood, most clinicians consider it a follicular adnexal neoplasm because the lesions often are connected to the pilosebaceous unit on microscopic observation.⁶ Although WD-like lesions arising from the oral mucosa have been reported,⁷ their etiology may be different from WD because the oral mucosa lacks hair follicles.⁸ The term warty leads to speculation of the contribution of human papillomavirus to the pathogenesis of WD, but this has been questioned due to the negative result of viral DNA detection from WD lesions by polymerase chain reaction analysis.² Therefore, the term follicular dyskeratoma has been suggested as a novel denomination that reflects its etiology more precisely.²  

The efficacy of topical treatment has not yet been established. Cryosurgery is another therapeutic option, but it sometimes fails.⁹ As performed in our patient, excisional biopsy is the most reasonable treatment option to obtain both complete removal and precise diagnosis.  
 

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Adults older than 65 years with inflammatory bowel diseases (IBD) had significantly higher rates of inpatient mortality, compared with those younger than 65 years, independent of factors including disease severity, based on data from more than 200,000 hospital admissions.

Older adults use a disproportionate share of health care resources, but data on outcomes among hospitalized older adults with gastrointestinal illness are limited, Jeffrey Schwartz, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote in the Journal of Clinical Gastroenterology.

“In particular, there remains a significant concern that elderly patients are more susceptible to the development of opportunistic infections and malignancy in the setting of biological therapy, which has evolved into the standard of care for IBD over the past 10 years,” they wrote.

In their study, the researchers identified 162,800 hospital admissions for Crohn’s disease and 96,450 admissions for ulcerative colitis. Of these, 20% and 30%, respectively, were older than 65 years, which the researchers designated as the geriatric group.

In a multivariate analysis, age older than 65 years was significantly associated with increased mortality in both Crohn’s disease (odds ratio, 3.47; 95% confidence interval, 2.72-4.44; P < .001) and ulcerative colitis (OR, 2.75; 95% CI, 2.16-3.49; P < .001). The association was independent of factors included comorbidities, admission type, hospital type, inpatient surgery, and IBD subtype.

The most frequent cause of death in both groups across all ages and disease subtypes was infections (approximately 80% for all groups). The total hospital length of stay was significantly longer for geriatric patients, compared with younger patients with Crohn’s disease, in multivariate analysis (average increase, 0.19 days; P = .009). The total charges also were significantly higher among geriatric Crohn’s disease patients, compared with younger patients (average increase, $2,467; P = .012). No significant differences in hospital stay or total charges appeared between geriatric and younger patients with ulcerative colitis.

The study findings were limited by several factors such as the inclusion of older patients with IBD who were hospitalized for other reasons and by the potential for increased mortality because of comorbidities among elderly patients, the researchers noted. However, the findings support the limited data from similar previous studies and showed greater inpatient mortality for older adults with IBD, compared with hospital inpatients overall.

“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, further studies are needed targeting geriatric patients with UC [ulcerative colitis] and CD [Crohn’s disease] to improve their overall management and quality of care to determine if this mortality risk can be reduced,” they concluded.
 

Tune in to risks in older adults

The study is important because the percentage of the population older than 65 years has been increasing; “at the same time, we are seeing more elderly patients being newly diagnosed with Crohn’s disease and ulcerative colitis,” said Russell D. Cohen, MD, of the University of Chicago, in an interview. “These patients are more vulnerable to complications of the diseases, such as infections, as well as complications from the medications used to treat these diseases.” However, older adults are often excluded from clinical trials and even from many observational studies in IBD, he noted.

“We have known from past studies that infections such as sepsis are a leading cause of death in our IBD patients,” said Dr. Cohen. “It is also understandable that those patients who have had complicated courses and those with other comorbidities have a higher mortality rate. However, what was surprising in the current study is that, even when the authors controlled for these factors, the geriatric patients still had two and three-quarters to three and a half times the mortality than those who were younger.”

The take-home message for clinicians is that “the geriatric patient with IBD is at a much higher rate for inpatient mortality, most commonly from infectious complications, than younger patients,” Dr. Cohen emphasized. “Quicker attention to what may seem minor but could become a potentially life-threatening infection is imperative. Caution with the use of multiple immune suppressing medications in older patients is paramount, as is timely surgical intervention in IBD patients in whom medications simply are not working.”
 

Focus research on infection prevention, cost burden

“More research should be directed at finding out whether these deadly infections could be prevented, perhaps by preventative ‘prophylactic’ antibiotics in the elderly patients, especially those on multiple immunosuppressive agents,” said Dr. Cohen. “In addition, research into the undue cost burden that these patients place on our health care system and counter that with better access to the newer, safer biological therapies [most of which Medicare does not cover] rather than corticosteroids.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Cohen disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb/Celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB Pharma.

SOURCE: Schwartz J et al. J Clin Gastroenterol. 2020 Nov 23. doi: 10.1097/MCG.0000000000001458.

Adults older than 65 years with inflammatory bowel diseases (IBD) had significantly higher rates of inpatient mortality, compared with those younger than 65 years, independent of factors including disease severity, based on data from more than 200,000 hospital admissions.

Older adults use a disproportionate share of health care resources, but data on outcomes among hospitalized older adults with gastrointestinal illness are limited, Jeffrey Schwartz, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote in the Journal of Clinical Gastroenterology.

“In particular, there remains a significant concern that elderly patients are more susceptible to the development of opportunistic infections and malignancy in the setting of biological therapy, which has evolved into the standard of care for IBD over the past 10 years,” they wrote.

In their study, the researchers identified 162,800 hospital admissions for Crohn’s disease and 96,450 admissions for ulcerative colitis. Of these, 20% and 30%, respectively, were older than 65 years, which the researchers designated as the geriatric group.

In a multivariate analysis, age older than 65 years was significantly associated with increased mortality in both Crohn’s disease (odds ratio, 3.47; 95% confidence interval, 2.72-4.44; P < .001) and ulcerative colitis (OR, 2.75; 95% CI, 2.16-3.49; P < .001). The association was independent of factors included comorbidities, admission type, hospital type, inpatient surgery, and IBD subtype.

The most frequent cause of death in both groups across all ages and disease subtypes was infections (approximately 80% for all groups). The total hospital length of stay was significantly longer for geriatric patients, compared with younger patients with Crohn’s disease, in multivariate analysis (average increase, 0.19 days; P = .009). The total charges also were significantly higher among geriatric Crohn’s disease patients, compared with younger patients (average increase, $2,467; P = .012). No significant differences in hospital stay or total charges appeared between geriatric and younger patients with ulcerative colitis.

The study findings were limited by several factors such as the inclusion of older patients with IBD who were hospitalized for other reasons and by the potential for increased mortality because of comorbidities among elderly patients, the researchers noted. However, the findings support the limited data from similar previous studies and showed greater inpatient mortality for older adults with IBD, compared with hospital inpatients overall.

“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, further studies are needed targeting geriatric patients with UC [ulcerative colitis] and CD [Crohn’s disease] to improve their overall management and quality of care to determine if this mortality risk can be reduced,” they concluded.
 

Tune in to risks in older adults

The study is important because the percentage of the population older than 65 years has been increasing; “at the same time, we are seeing more elderly patients being newly diagnosed with Crohn’s disease and ulcerative colitis,” said Russell D. Cohen, MD, of the University of Chicago, in an interview. “These patients are more vulnerable to complications of the diseases, such as infections, as well as complications from the medications used to treat these diseases.” However, older adults are often excluded from clinical trials and even from many observational studies in IBD, he noted.

“We have known from past studies that infections such as sepsis are a leading cause of death in our IBD patients,” said Dr. Cohen. “It is also understandable that those patients who have had complicated courses and those with other comorbidities have a higher mortality rate. However, what was surprising in the current study is that, even when the authors controlled for these factors, the geriatric patients still had two and three-quarters to three and a half times the mortality than those who were younger.”

The take-home message for clinicians is that “the geriatric patient with IBD is at a much higher rate for inpatient mortality, most commonly from infectious complications, than younger patients,” Dr. Cohen emphasized. “Quicker attention to what may seem minor but could become a potentially life-threatening infection is imperative. Caution with the use of multiple immune suppressing medications in older patients is paramount, as is timely surgical intervention in IBD patients in whom medications simply are not working.”
 

Focus research on infection prevention, cost burden

“More research should be directed at finding out whether these deadly infections could be prevented, perhaps by preventative ‘prophylactic’ antibiotics in the elderly patients, especially those on multiple immunosuppressive agents,” said Dr. Cohen. “In addition, research into the undue cost burden that these patients place on our health care system and counter that with better access to the newer, safer biological therapies [most of which Medicare does not cover] rather than corticosteroids.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Cohen disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb/Celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB Pharma.

SOURCE: Schwartz J et al. J Clin Gastroenterol. 2020 Nov 23. doi: 10.1097/MCG.0000000000001458.

Adults older than 65 years with inflammatory bowel diseases (IBD) had significantly higher rates of inpatient mortality, compared with those younger than 65 years, independent of factors including disease severity, based on data from more than 200,000 hospital admissions.

Older adults use a disproportionate share of health care resources, but data on outcomes among hospitalized older adults with gastrointestinal illness are limited, Jeffrey Schwartz, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote in the Journal of Clinical Gastroenterology.

“In particular, there remains a significant concern that elderly patients are more susceptible to the development of opportunistic infections and malignancy in the setting of biological therapy, which has evolved into the standard of care for IBD over the past 10 years,” they wrote.

In their study, the researchers identified 162,800 hospital admissions for Crohn’s disease and 96,450 admissions for ulcerative colitis. Of these, 20% and 30%, respectively, were older than 65 years, which the researchers designated as the geriatric group.

In a multivariate analysis, age older than 65 years was significantly associated with increased mortality in both Crohn’s disease (odds ratio, 3.47; 95% confidence interval, 2.72-4.44; P < .001) and ulcerative colitis (OR, 2.75; 95% CI, 2.16-3.49; P < .001). The association was independent of factors included comorbidities, admission type, hospital type, inpatient surgery, and IBD subtype.

The most frequent cause of death in both groups across all ages and disease subtypes was infections (approximately 80% for all groups). The total hospital length of stay was significantly longer for geriatric patients, compared with younger patients with Crohn’s disease, in multivariate analysis (average increase, 0.19 days; P = .009). The total charges also were significantly higher among geriatric Crohn’s disease patients, compared with younger patients (average increase, $2,467; P = .012). No significant differences in hospital stay or total charges appeared between geriatric and younger patients with ulcerative colitis.

The study findings were limited by several factors such as the inclusion of older patients with IBD who were hospitalized for other reasons and by the potential for increased mortality because of comorbidities among elderly patients, the researchers noted. However, the findings support the limited data from similar previous studies and showed greater inpatient mortality for older adults with IBD, compared with hospital inpatients overall.

“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, further studies are needed targeting geriatric patients with UC [ulcerative colitis] and CD [Crohn’s disease] to improve their overall management and quality of care to determine if this mortality risk can be reduced,” they concluded.
 

Tune in to risks in older adults

The study is important because the percentage of the population older than 65 years has been increasing; “at the same time, we are seeing more elderly patients being newly diagnosed with Crohn’s disease and ulcerative colitis,” said Russell D. Cohen, MD, of the University of Chicago, in an interview. “These patients are more vulnerable to complications of the diseases, such as infections, as well as complications from the medications used to treat these diseases.” However, older adults are often excluded from clinical trials and even from many observational studies in IBD, he noted.

“We have known from past studies that infections such as sepsis are a leading cause of death in our IBD patients,” said Dr. Cohen. “It is also understandable that those patients who have had complicated courses and those with other comorbidities have a higher mortality rate. However, what was surprising in the current study is that, even when the authors controlled for these factors, the geriatric patients still had two and three-quarters to three and a half times the mortality than those who were younger.”

The take-home message for clinicians is that “the geriatric patient with IBD is at a much higher rate for inpatient mortality, most commonly from infectious complications, than younger patients,” Dr. Cohen emphasized. “Quicker attention to what may seem minor but could become a potentially life-threatening infection is imperative. Caution with the use of multiple immune suppressing medications in older patients is paramount, as is timely surgical intervention in IBD patients in whom medications simply are not working.”
 

Focus research on infection prevention, cost burden

“More research should be directed at finding out whether these deadly infections could be prevented, perhaps by preventative ‘prophylactic’ antibiotics in the elderly patients, especially those on multiple immunosuppressive agents,” said Dr. Cohen. “In addition, research into the undue cost burden that these patients place on our health care system and counter that with better access to the newer, safer biological therapies [most of which Medicare does not cover] rather than corticosteroids.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Cohen disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb/Celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB Pharma.

SOURCE: Schwartz J et al. J Clin Gastroenterol. 2020 Nov 23. doi: 10.1097/MCG.0000000000001458.

The American Gastroenterological Association has published a Clinical Practice Update for management of inflammatory bowel disease (IBD) in elderly patients, including 15 best practice advice statements.

According to lead author Ashwin N. Ananthakrishnan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues, this topic is becoming increasingly relevant, as the population is aging, and prevalence of IBD among elderly is rising approximately 5% per year.

“Up to 15% of IBD in North America and Asia is diagnosed after the age of 60 years,” the investigators wrote in Gastroenterology.

Dr. Ananthakrishnan and colleagues noted that “care of elderly IBD patients poses unique challenges with respect to diagnosis and therapeutic decision-making.”

Challenges include greater frequency of comorbidities, increased risk of infection with anti–tumor necrosis factor therapy, increased risk of lymphoma with thiopurine therapy, greater likelihood of surgical complications, and, for Crohn’s disease, an elevated mortality rate, according to the update.

Another challenge is a lack of data.

“It should be noted that most clinical data to inform these practices are based on observational data or indirect evidence as elderly IBD patients comprise a very small proportion of subjects enrolled in IBD clinical trials or long-term pharmacovigilance initiatives,” the investigators wrote.

With this in mind, the update offers guidance for diagnosis, treatment, and ongoing health maintenance.
 

Diagnosis

Dr. Ananthakrishnan and colleagues first suggested that clinicians remain vigilant for IBD in elderly people, in consideration of the 15% prevalence rate in this subpopulation.

For elderly individuals with a low probability of IBD, the investigators recommended fecal calprotectin or lactoferrin to determine if endoscopy is needed. For elderly patients with chronic diarrhea or hematochezia, plus moderate to high suspicion of IBD, colorectal neoplasia, or microscopic colitis, they recommended colonoscopy.

Lastly, the expert panel suggested that elderly patients presenting with segmental left-sided colitis and diverticulosis may also have Crohn’s disease or IBD unclassified.
 

Treatment

The clinical practice update offers 10 best practice statements for treating elderly patients with IBD. There is a recurring emphasis on treatment personalization, which should be informed by patient goals and priorities, risk/presence of severe disease, chronological age, functional status, independence, comorbidities, frailty, and several other age-associated risk factors (e.g., venous thromboembolism).

Concerning specific therapies, the investigators cautioned against systemic corticosteroids for maintenance therapy; instead, nonsystemic corticosteroids (e.g., budesonide) are favored, or possibly early biological therapy if budesonide is not indicated. When selecting a biologic, Dr. Ananthakrishnan and colleagues recommended those associated with a lower risk of malignancy and infection (e.g., ustekinumab or vedolizumab).

The advantages of thiopurine monotherapy being oral, relatively inexpensive compared to biologicals and having a long track record of success in maintenance of remission must be balanced against the need for ongoing serological monitoring, and increased risk of some malignancies.

Finally, the expert panel recommended that all elderly patients receive multidisciplinary care, which may include primary care providers, mental health professionals, nutritionists, and other specialists. It may also be productive to consult with family and caregivers during treatment planning.

Health maintenance

The last two best practice advice statements concern health maintenance.

First, the investigators recommended that elderly patients with IBD adhere to vaccination schedules, including herpes zoster, pneumococcus, and influenza vaccines, ideally, before starting immunosuppression.

Second, Dr. Ananthakrishnan and colleagues advised that cessation of colorectal cancer surveillance may be considered in elderly patients with IBD; however, this decision should take into account a variety of factors, including comorbidities, age, life expectancy, likelihood of endoscopic resection, and surgical candidacy.

The review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Gilead, Sun Pharma, Kyn Therapeutics, and others.

SOURCE: Ananthakrishnan AN et al. Gastroenterology. 2020 Sep 30. doi: 10.1053/j.gastro.2020.08.060.

This story was updated on 12/4/2020.

The American Gastroenterological Association has published a Clinical Practice Update for management of inflammatory bowel disease (IBD) in elderly patients, including 15 best practice advice statements.

According to lead author Ashwin N. Ananthakrishnan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues, this topic is becoming increasingly relevant, as the population is aging, and prevalence of IBD among elderly is rising approximately 5% per year.

“Up to 15% of IBD in North America and Asia is diagnosed after the age of 60 years,” the investigators wrote in Gastroenterology.

Dr. Ananthakrishnan and colleagues noted that “care of elderly IBD patients poses unique challenges with respect to diagnosis and therapeutic decision-making.”

Challenges include greater frequency of comorbidities, increased risk of infection with anti–tumor necrosis factor therapy, increased risk of lymphoma with thiopurine therapy, greater likelihood of surgical complications, and, for Crohn’s disease, an elevated mortality rate, according to the update.

Another challenge is a lack of data.

“It should be noted that most clinical data to inform these practices are based on observational data or indirect evidence as elderly IBD patients comprise a very small proportion of subjects enrolled in IBD clinical trials or long-term pharmacovigilance initiatives,” the investigators wrote.

With this in mind, the update offers guidance for diagnosis, treatment, and ongoing health maintenance.
 

Diagnosis

Dr. Ananthakrishnan and colleagues first suggested that clinicians remain vigilant for IBD in elderly people, in consideration of the 15% prevalence rate in this subpopulation.

For elderly individuals with a low probability of IBD, the investigators recommended fecal calprotectin or lactoferrin to determine if endoscopy is needed. For elderly patients with chronic diarrhea or hematochezia, plus moderate to high suspicion of IBD, colorectal neoplasia, or microscopic colitis, they recommended colonoscopy.

Lastly, the expert panel suggested that elderly patients presenting with segmental left-sided colitis and diverticulosis may also have Crohn’s disease or IBD unclassified.
 

Treatment

The clinical practice update offers 10 best practice statements for treating elderly patients with IBD. There is a recurring emphasis on treatment personalization, which should be informed by patient goals and priorities, risk/presence of severe disease, chronological age, functional status, independence, comorbidities, frailty, and several other age-associated risk factors (e.g., venous thromboembolism).

Concerning specific therapies, the investigators cautioned against systemic corticosteroids for maintenance therapy; instead, nonsystemic corticosteroids (e.g., budesonide) are favored, or possibly early biological therapy if budesonide is not indicated. When selecting a biologic, Dr. Ananthakrishnan and colleagues recommended those associated with a lower risk of malignancy and infection (e.g., ustekinumab or vedolizumab).

The advantages of thiopurine monotherapy being oral, relatively inexpensive compared to biologicals and having a long track record of success in maintenance of remission must be balanced against the need for ongoing serological monitoring, and increased risk of some malignancies.

Finally, the expert panel recommended that all elderly patients receive multidisciplinary care, which may include primary care providers, mental health professionals, nutritionists, and other specialists. It may also be productive to consult with family and caregivers during treatment planning.

Health maintenance

The last two best practice advice statements concern health maintenance.

First, the investigators recommended that elderly patients with IBD adhere to vaccination schedules, including herpes zoster, pneumococcus, and influenza vaccines, ideally, before starting immunosuppression.

Second, Dr. Ananthakrishnan and colleagues advised that cessation of colorectal cancer surveillance may be considered in elderly patients with IBD; however, this decision should take into account a variety of factors, including comorbidities, age, life expectancy, likelihood of endoscopic resection, and surgical candidacy.

The review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Gilead, Sun Pharma, Kyn Therapeutics, and others.

SOURCE: Ananthakrishnan AN et al. Gastroenterology. 2020 Sep 30. doi: 10.1053/j.gastro.2020.08.060.

This story was updated on 12/4/2020.

The American Gastroenterological Association has published a Clinical Practice Update for management of inflammatory bowel disease (IBD) in elderly patients, including 15 best practice advice statements.

According to lead author Ashwin N. Ananthakrishnan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues, this topic is becoming increasingly relevant, as the population is aging, and prevalence of IBD among elderly is rising approximately 5% per year.

“Up to 15% of IBD in North America and Asia is diagnosed after the age of 60 years,” the investigators wrote in Gastroenterology.

Dr. Ananthakrishnan and colleagues noted that “care of elderly IBD patients poses unique challenges with respect to diagnosis and therapeutic decision-making.”

Challenges include greater frequency of comorbidities, increased risk of infection with anti–tumor necrosis factor therapy, increased risk of lymphoma with thiopurine therapy, greater likelihood of surgical complications, and, for Crohn’s disease, an elevated mortality rate, according to the update.

Another challenge is a lack of data.

“It should be noted that most clinical data to inform these practices are based on observational data or indirect evidence as elderly IBD patients comprise a very small proportion of subjects enrolled in IBD clinical trials or long-term pharmacovigilance initiatives,” the investigators wrote.

With this in mind, the update offers guidance for diagnosis, treatment, and ongoing health maintenance.
 

Diagnosis

Dr. Ananthakrishnan and colleagues first suggested that clinicians remain vigilant for IBD in elderly people, in consideration of the 15% prevalence rate in this subpopulation.

For elderly individuals with a low probability of IBD, the investigators recommended fecal calprotectin or lactoferrin to determine if endoscopy is needed. For elderly patients with chronic diarrhea or hematochezia, plus moderate to high suspicion of IBD, colorectal neoplasia, or microscopic colitis, they recommended colonoscopy.

Lastly, the expert panel suggested that elderly patients presenting with segmental left-sided colitis and diverticulosis may also have Crohn’s disease or IBD unclassified.
 

Treatment

The clinical practice update offers 10 best practice statements for treating elderly patients with IBD. There is a recurring emphasis on treatment personalization, which should be informed by patient goals and priorities, risk/presence of severe disease, chronological age, functional status, independence, comorbidities, frailty, and several other age-associated risk factors (e.g., venous thromboembolism).

Concerning specific therapies, the investigators cautioned against systemic corticosteroids for maintenance therapy; instead, nonsystemic corticosteroids (e.g., budesonide) are favored, or possibly early biological therapy if budesonide is not indicated. When selecting a biologic, Dr. Ananthakrishnan and colleagues recommended those associated with a lower risk of malignancy and infection (e.g., ustekinumab or vedolizumab).

The advantages of thiopurine monotherapy being oral, relatively inexpensive compared to biologicals and having a long track record of success in maintenance of remission must be balanced against the need for ongoing serological monitoring, and increased risk of some malignancies.

Finally, the expert panel recommended that all elderly patients receive multidisciplinary care, which may include primary care providers, mental health professionals, nutritionists, and other specialists. It may also be productive to consult with family and caregivers during treatment planning.

Health maintenance

The last two best practice advice statements concern health maintenance.

First, the investigators recommended that elderly patients with IBD adhere to vaccination schedules, including herpes zoster, pneumococcus, and influenza vaccines, ideally, before starting immunosuppression.

Second, Dr. Ananthakrishnan and colleagues advised that cessation of colorectal cancer surveillance may be considered in elderly patients with IBD; however, this decision should take into account a variety of factors, including comorbidities, age, life expectancy, likelihood of endoscopic resection, and surgical candidacy.

The review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Gilead, Sun Pharma, Kyn Therapeutics, and others.

SOURCE: Ananthakrishnan AN et al. Gastroenterology. 2020 Sep 30. doi: 10.1053/j.gastro.2020.08.060.

This story was updated on 12/4/2020.

ANSWER

The correct answer is Grover disease (choice “c”).

DISCUSSION

Grover disease—also known as transient acantholytic dermatosis—was first described in 1975 by Ralph Grover, MD, and is now recognized as a relatively common condition, especially in White men older than 40. Its appearance on darker skin is unusual. The morphologic presentation seen in this case is fairly typical, though most patients complain more about itching than this patient did.

The actual cause of Grover disease is unknown. Heat, sweat, and sunlight are suspected triggers. Its appearance can be associated with certain medications, recent treatment with ionizing radiation, or end-stage renal failure.

Biopsy is the key to diagnosis of Grover disease, especially in the context of the clinical presentation. This method also serves to rule out the other items in the differential.

Tinea corporis (choice “a”) was ruled out by the KOH as well as the rash’s appearance. Darier disease (choice “b”)—otherwise known as keratosis follicularis—is an inherited dermatosis that presents with multiple findings on skin, nails, and mucous membranes; however, the papulosquamous rash would be far more coarse than what manifests in Grover disease, and it would have manifested at a much earlier age. While folliculitis (choice “d”) was a possibility in this patient, the biopsy ruled it out.

TREATMENT

Grover disease is notoriously difficult to treat. Although it is described as a “transient” dermatosis, it can last months to years despite all therapeutic efforts.

This patient was treated with a stronger topical steroid (0.05% betamethasone cream) twice a day and minocycline (100 mg/d) for 2 months. These cleared his rash.

ANSWER

The correct answer is Grover disease (choice “c”).

DISCUSSION

Grover disease—also known as transient acantholytic dermatosis—was first described in 1975 by Ralph Grover, MD, and is now recognized as a relatively common condition, especially in White men older than 40. Its appearance on darker skin is unusual. The morphologic presentation seen in this case is fairly typical, though most patients complain more about itching than this patient did.

The actual cause of Grover disease is unknown. Heat, sweat, and sunlight are suspected triggers. Its appearance can be associated with certain medications, recent treatment with ionizing radiation, or end-stage renal failure.

Biopsy is the key to diagnosis of Grover disease, especially in the context of the clinical presentation. This method also serves to rule out the other items in the differential.

Tinea corporis (choice “a”) was ruled out by the KOH as well as the rash’s appearance. Darier disease (choice “b”)—otherwise known as keratosis follicularis—is an inherited dermatosis that presents with multiple findings on skin, nails, and mucous membranes; however, the papulosquamous rash would be far more coarse than what manifests in Grover disease, and it would have manifested at a much earlier age. While folliculitis (choice “d”) was a possibility in this patient, the biopsy ruled it out.

TREATMENT

Grover disease is notoriously difficult to treat. Although it is described as a “transient” dermatosis, it can last months to years despite all therapeutic efforts.

This patient was treated with a stronger topical steroid (0.05% betamethasone cream) twice a day and minocycline (100 mg/d) for 2 months. These cleared his rash.

ANSWER

The correct answer is Grover disease (choice “c”).

DISCUSSION

Grover disease—also known as transient acantholytic dermatosis—was first described in 1975 by Ralph Grover, MD, and is now recognized as a relatively common condition, especially in White men older than 40. Its appearance on darker skin is unusual. The morphologic presentation seen in this case is fairly typical, though most patients complain more about itching than this patient did.

The actual cause of Grover disease is unknown. Heat, sweat, and sunlight are suspected triggers. Its appearance can be associated with certain medications, recent treatment with ionizing radiation, or end-stage renal failure.

Biopsy is the key to diagnosis of Grover disease, especially in the context of the clinical presentation. This method also serves to rule out the other items in the differential.

Tinea corporis (choice “a”) was ruled out by the KOH as well as the rash’s appearance. Darier disease (choice “b”)—otherwise known as keratosis follicularis—is an inherited dermatosis that presents with multiple findings on skin, nails, and mucous membranes; however, the papulosquamous rash would be far more coarse than what manifests in Grover disease, and it would have manifested at a much earlier age. While folliculitis (choice “d”) was a possibility in this patient, the biopsy ruled it out.

TREATMENT

Grover disease is notoriously difficult to treat. Although it is described as a “transient” dermatosis, it can last months to years despite all therapeutic efforts.

This patient was treated with a stronger topical steroid (0.05% betamethasone cream) twice a day and minocycline (100 mg/d) for 2 months. These cleared his rash.

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.

[email protected]