Dermatology

HONOLULU – In the clinical experience of John S. Barbieri, MD, MBA, cheilitis occurs in nearly all patients taking any dose of isotretinoin.

“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”

According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).

“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”

Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.

“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”

In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .

One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.

Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).

A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.

In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.

HONOLULU – In the clinical experience of John S. Barbieri, MD, MBA, cheilitis occurs in nearly all patients taking any dose of isotretinoin.

“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”

According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).

“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”

Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.

“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”

In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .

One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.

Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).

A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.

In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.

HONOLULU – In the clinical experience of John S. Barbieri, MD, MBA, cheilitis occurs in nearly all patients taking any dose of isotretinoin.

“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”

According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).

“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”

Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.

“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”

In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .

One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.

Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).

A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.

In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

Antibiotics were associated with 28% of all cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, according to the first meta-analysis to examine the worldwide prevalence of SJS/TEN in connection with antibiotics.

“SJS/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk,” Erika Yue Lee, MD, and associates wrote in JAMA Dermatology.

Their analysis, which involved 38 studies published since 1987 with 2,917 patients from more than 20 countries, showed that 86% of all SJS/TEN cases were associated with a single drug, with the rest involving multiple drug triggers, infections, or other causes. More than a quarter (28%) of those patients had used an antibiotic, and the sulfonamides were the class most often triggering SJS/TEN, said Dr. Lee of the University of Toronto and associates.

Sulfonamides were responsible for 32% of the antibiotic-associated cases, which works out to 11% of all SJS/TEN cases included in the analysis. Penicillins were next with 22% of all antibiotic-associated cases, followed by the cephalosporins (11%), fluoroquinolones (4%), and macrolides (2%), the investigators reported.

A subgroup analysis conducted by age indicated that “there was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups,” they noted.

There were differences, however, among the various antibiotic classes. Sulfonamides represented 54% of antibiotic-triggered reactions in children, compared with 25% in adults, but adults were significantly more likely to have cephalosporin (23%) and fluoroquinolone (5%) involvement than were children (2% and 0, respectively). Macrolide-induced SJS/TEN was more common in children (18% vs. 1%), while the penicillin rate was 18% for both age groups, Dr. Lee and associates said.

A second subgroup analysis establishing the proportion of antibiotic-induced SJS/TEN by continent ranked Australia highest with 43%, but that was based on only one study of 42 patients. North America was slightly lower at 37%, but the analysis included 14 studies and 932 patients. Asia’s 16 studies and 1,298 patients were divided into three regions, with the lowest being the southeast at 16%, according to the researchers.

“Global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes,” they wrote, but “antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.”

One of Dr. Lee’s associates has received personal fees from Janssen, AstraZeneca, UpToDate, Verve, BioCryst, Regeneron Pharmaceuticals, and Novavax and has served as codirector of IIID Pty Ltd, which holds a patent for HLA-B*57:01 testing and has a patent pending for detection of HLA-A*32:01 in connection with diagnosing drug reaction without any financial remuneration outside this study.

Antibiotics were associated with 28% of all cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, according to the first meta-analysis to examine the worldwide prevalence of SJS/TEN in connection with antibiotics.

“SJS/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk,” Erika Yue Lee, MD, and associates wrote in JAMA Dermatology.

Their analysis, which involved 38 studies published since 1987 with 2,917 patients from more than 20 countries, showed that 86% of all SJS/TEN cases were associated with a single drug, with the rest involving multiple drug triggers, infections, or other causes. More than a quarter (28%) of those patients had used an antibiotic, and the sulfonamides were the class most often triggering SJS/TEN, said Dr. Lee of the University of Toronto and associates.

Sulfonamides were responsible for 32% of the antibiotic-associated cases, which works out to 11% of all SJS/TEN cases included in the analysis. Penicillins were next with 22% of all antibiotic-associated cases, followed by the cephalosporins (11%), fluoroquinolones (4%), and macrolides (2%), the investigators reported.

A subgroup analysis conducted by age indicated that “there was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups,” they noted.

There were differences, however, among the various antibiotic classes. Sulfonamides represented 54% of antibiotic-triggered reactions in children, compared with 25% in adults, but adults were significantly more likely to have cephalosporin (23%) and fluoroquinolone (5%) involvement than were children (2% and 0, respectively). Macrolide-induced SJS/TEN was more common in children (18% vs. 1%), while the penicillin rate was 18% for both age groups, Dr. Lee and associates said.

A second subgroup analysis establishing the proportion of antibiotic-induced SJS/TEN by continent ranked Australia highest with 43%, but that was based on only one study of 42 patients. North America was slightly lower at 37%, but the analysis included 14 studies and 932 patients. Asia’s 16 studies and 1,298 patients were divided into three regions, with the lowest being the southeast at 16%, according to the researchers.

“Global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes,” they wrote, but “antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.”

One of Dr. Lee’s associates has received personal fees from Janssen, AstraZeneca, UpToDate, Verve, BioCryst, Regeneron Pharmaceuticals, and Novavax and has served as codirector of IIID Pty Ltd, which holds a patent for HLA-B*57:01 testing and has a patent pending for detection of HLA-A*32:01 in connection with diagnosing drug reaction without any financial remuneration outside this study.

Antibiotics were associated with 28% of all cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, according to the first meta-analysis to examine the worldwide prevalence of SJS/TEN in connection with antibiotics.

“SJS/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk,” Erika Yue Lee, MD, and associates wrote in JAMA Dermatology.

Their analysis, which involved 38 studies published since 1987 with 2,917 patients from more than 20 countries, showed that 86% of all SJS/TEN cases were associated with a single drug, with the rest involving multiple drug triggers, infections, or other causes. More than a quarter (28%) of those patients had used an antibiotic, and the sulfonamides were the class most often triggering SJS/TEN, said Dr. Lee of the University of Toronto and associates.

Sulfonamides were responsible for 32% of the antibiotic-associated cases, which works out to 11% of all SJS/TEN cases included in the analysis. Penicillins were next with 22% of all antibiotic-associated cases, followed by the cephalosporins (11%), fluoroquinolones (4%), and macrolides (2%), the investigators reported.

A subgroup analysis conducted by age indicated that “there was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups,” they noted.

There were differences, however, among the various antibiotic classes. Sulfonamides represented 54% of antibiotic-triggered reactions in children, compared with 25% in adults, but adults were significantly more likely to have cephalosporin (23%) and fluoroquinolone (5%) involvement than were children (2% and 0, respectively). Macrolide-induced SJS/TEN was more common in children (18% vs. 1%), while the penicillin rate was 18% for both age groups, Dr. Lee and associates said.

A second subgroup analysis establishing the proportion of antibiotic-induced SJS/TEN by continent ranked Australia highest with 43%, but that was based on only one study of 42 patients. North America was slightly lower at 37%, but the analysis included 14 studies and 932 patients. Asia’s 16 studies and 1,298 patients were divided into three regions, with the lowest being the southeast at 16%, according to the researchers.

“Global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes,” they wrote, but “antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.”

One of Dr. Lee’s associates has received personal fees from Janssen, AstraZeneca, UpToDate, Verve, BioCryst, Regeneron Pharmaceuticals, and Novavax and has served as codirector of IIID Pty Ltd, which holds a patent for HLA-B*57:01 testing and has a patent pending for detection of HLA-A*32:01 in connection with diagnosing drug reaction without any financial remuneration outside this study.

ORLANDO – From differentiating them from mimics to choosing the best treatment course, Molly Hinshaw, MD, reviewed some of the ins and outs of managing nail disorders at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dr. Hinshaw, professor of dermatology at the University of Wisconsin, Madison, reviewed several disorders and provided guidance on diagnosis, and achieving the best outcomes for patients.

Pyogenic granuloma (PG) in the nail: These are benign vascular tumors that can mimic more serious conditions, Dr. Hinshaw said. In adults, PG requires a histologic diagnosis, she said.

“So these all really should have a biopsy,” because of potential confusion with amelanotic melanoma or squamous cell carcinoma, she said, although in children, a biopsy is likely not necessary.

Treatment with topical beta-blockers can be effective for PG, she said, and avoids the scarring seen with surgical removal. “These are benign conditions – we want them to go away, but we want these patients to have a functional nail thereafter.”

Periungual or subungual warts: For these warts, which are alongside or under the nail, destructive approaches can cause scarring of the nail bed and are far from optimal, she said.

“We’d like to avoid that, of course.” Therefore, treatments such as lasers and liquid nitrogen “would be much further down, if at all, on my list,” she said.

Injections of the antiviral cidofovir, into the dermis right under the wart, can be highly effective, and one or two treatments is often enough, Dr. Hinshaw said. Sometimes, local anesthesia isn’t even needed for the injection, she said. “This is a wonderful option,” she added.

Dr. Hinshaw is co-owner and chief medical officer of Acure.

ORLANDO – From differentiating them from mimics to choosing the best treatment course, Molly Hinshaw, MD, reviewed some of the ins and outs of managing nail disorders at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dr. Hinshaw, professor of dermatology at the University of Wisconsin, Madison, reviewed several disorders and provided guidance on diagnosis, and achieving the best outcomes for patients.

Pyogenic granuloma (PG) in the nail: These are benign vascular tumors that can mimic more serious conditions, Dr. Hinshaw said. In adults, PG requires a histologic diagnosis, she said.

“So these all really should have a biopsy,” because of potential confusion with amelanotic melanoma or squamous cell carcinoma, she said, although in children, a biopsy is likely not necessary.

Treatment with topical beta-blockers can be effective for PG, she said, and avoids the scarring seen with surgical removal. “These are benign conditions – we want them to go away, but we want these patients to have a functional nail thereafter.”

Periungual or subungual warts: For these warts, which are alongside or under the nail, destructive approaches can cause scarring of the nail bed and are far from optimal, she said.

“We’d like to avoid that, of course.” Therefore, treatments such as lasers and liquid nitrogen “would be much further down, if at all, on my list,” she said.

Injections of the antiviral cidofovir, into the dermis right under the wart, can be highly effective, and one or two treatments is often enough, Dr. Hinshaw said. Sometimes, local anesthesia isn’t even needed for the injection, she said. “This is a wonderful option,” she added.

Dr. Hinshaw is co-owner and chief medical officer of Acure.

ORLANDO – From differentiating them from mimics to choosing the best treatment course, Molly Hinshaw, MD, reviewed some of the ins and outs of managing nail disorders at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dr. Hinshaw, professor of dermatology at the University of Wisconsin, Madison, reviewed several disorders and provided guidance on diagnosis, and achieving the best outcomes for patients.

Pyogenic granuloma (PG) in the nail: These are benign vascular tumors that can mimic more serious conditions, Dr. Hinshaw said. In adults, PG requires a histologic diagnosis, she said.

“So these all really should have a biopsy,” because of potential confusion with amelanotic melanoma or squamous cell carcinoma, she said, although in children, a biopsy is likely not necessary.

Treatment with topical beta-blockers can be effective for PG, she said, and avoids the scarring seen with surgical removal. “These are benign conditions – we want them to go away, but we want these patients to have a functional nail thereafter.”

Periungual or subungual warts: For these warts, which are alongside or under the nail, destructive approaches can cause scarring of the nail bed and are far from optimal, she said.

“We’d like to avoid that, of course.” Therefore, treatments such as lasers and liquid nitrogen “would be much further down, if at all, on my list,” she said.

Injections of the antiviral cidofovir, into the dermis right under the wart, can be highly effective, and one or two treatments is often enough, Dr. Hinshaw said. Sometimes, local anesthesia isn’t even needed for the injection, she said. “This is a wonderful option,” she added.

Dr. Hinshaw is co-owner and chief medical officer of Acure.

SAN DIEGO – When parents bring their children to Caroline Piggott, MD, to evaluate a suspicious mole on the scalp or other body location, the vast majority turn out to be benign, because the incidence of melanoma is rare, especially before puberty.

“Only 1%-2% of all melanomas in the world are in children, so most of my job is to provide reassurance,” Dr. Piggott, a pediatric dermatologist at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “Few pediatric studies exist. Why? Because children are excluded from most melanoma clinical trials. Our management is based mainly on adult National Comprehensive Cancer Network guidelines.”

Doug Brunk/MDedge News

To help parents identify melanoma, clinicians typically recommend the “ABCDE” rule, for Asymmetry, Border irregularity, Color variation (especially dark or multiple colors), Diameter greater than 6 mm, and Evolving (is it changing, bleeding or painful?).

While Dr. Piggott considers the standard ABCDE rules as important – especially in older children and teenagers – researchers led by Kelly M. Cordoro, MD, professor of dermatology at the University of California, San Francisco, proposed a modified ABCD criteria based on evaluating a cohort of 60 children who were diagnosed with melanoma and 10 who were diagnosed with ambiguous melanocytic tumors treated as melanoma before age 20 years at UCSF from 1984 to 2009.

The researchers divided patients into two groups: those aged 0-10 years (19; group A) and those aged 11-19 years (51; group B), and found that 60% of children in group A and 40% of those in group B did not present with conventional ABCDE criteria for children. Of the 60 melanoma patients, 10 died. Of these, 9 were older than age 10, and 70% had amelanotic lesions. Based on their analysis of clinical, histopathologic, and outcomes data, Dr. Cordoro and colleagues proposed additional ABCD criteria in which A stands for stands Amelanotic; B for Bleeding or Bump; C for Color uniformity, and D for De novo or any Diameter.

“This doesn’t mean you throw the old ABCDE criteria out the window,” Dr. Piggott said. “It means that you use this modified criteria in conjunction with the conventional ABCDE rules.”

Risk factors for melanoma in children are like those in adults, and include a family history of melanoma, large/giant congenital nevi, the presence of many atypical appearing nevi, having Fitzpatrick skin types I or II, a history of blistering sunburns, and the presence of genetic anomalies such as xeroderma pigmentosum.

According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program, melanoma incidence increased in all individuals in the United States aged 0-19 years from 1973 to 2009. Key risk factors included White race, female sex, and living in a SEER registry categorized as low UVB exposure. Over the study period, boys experienced increased incidence rates of melanoma on the face and trunk, while girls experienced increased incidence rates of melanoma on the lower limbs and hip.

More recently, researchers extracted data from 988,103 cases of invasive melanoma in the 2001-2015 SEER database to determine the age-specific incidence of melanoma in the United States. In 2015, 83,362 cases of invasive melanoma were reported for all ages. Of these, only 67 cases were younger than age 10, while 251 were between the ages of 10 and 19 and 1,973 were young adults between the ages of 20 and 29.

In other findings, between 2006 and 2015, the overall incidence of invasive melanoma for all ages increased from 200 million to 229 cases per million person-years. “However, there were statistically significant decreases in melanoma incidence for individuals aged 10-19 years and for those aged 10-29 years,” said Dr. Piggott, who was not involved with the study. “The hypothesis is that public health efforts encouraging against sun exposure and tanning bed use may be influencing melanoma incidence in younger populations. What is interesting, though, is that young adult women have twice the melanoma risk as young adult men.”

In a separate study, researchers prospectively followed 60 melanoma-prone families for up to 40 years to evaluate the risk of pediatric melanoma in those with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. Regardless of their CDKN2A status, the percentage of pediatric melanoma cases was 6- to 28-fold higher among melanoma-prone families, compared with the general population. In addition, families who were CDKN2A positive had a significantly higher rate of pediatric melanoma cases compared with those who were CDKN2A negative (11.1% vs. 2.5%; P = .004).

As for treating pediatric melanoma, the standard of care is similar to that for adults: usually wide local surgical excision of the primary lesion, depending on depth. Clinicians typically follow adult parameters for sentinel lymph node biopsy, such as lesion depth and ulceration.

“We know that a positive sentinel node does have prognostic value, but there is great debate on whether to do a lymph node dissection if the sentinel lymph node is positive,” Dr. Piggott said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “This is determined on a case-by-case basis. We consider factors such as, are the nodes palpable? Is there evidence on ultrasound? But there are no formal guidelines.”

Limited studies of systemic therapy in children exist because this population is excluded from most melanoma clinical trials. “In the past, interferon was sometimes used,” she said. “But in recent years, as with adults, we have started to use targeted immunologic therapy. This is usually managed by a tertiary academic oncology center.”

The chance of surviving pediatric melanoma is good if caught early. As in adults, the stage correlates strongly with survival, and distant metastases carry a poor prognosis.

In 2020, researchers published a retrospective, multicenter review of 38 cases of fatal pediatric melanoma between 1994 and 2017. The analysis was limited to individuals 20 years of age and younger who were cared for at 12 academic medical centers. Of the 38 patients, 42% were male, 58% were female, and 57% were White. In addition, 19% were Hispanic, “which is a larger percentage than fatalities in adult [Hispanic] populations with melanoma,” said Dr. Piggott, who was not involved in the study.

The mean age at diagnosis was 12.7 years, the mean age at death was 15.6 , and the mean survival time after diagnosis was about 35 months. Of the 16 cases with known identifiable subtypes, 50% were nodular, 31% were superficial spreading, and 19% were spitzoid melanoma. In addition, one-quarter of melanomas arose in association with congenital melanocytic nevi.

“The good news is that there are only 38 total cases of fatal pediatric melanoma between 12 academic centers over a 23-year period,” Dr. Piggott said. “Thanks goodness the number is that low.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO – When parents bring their children to Caroline Piggott, MD, to evaluate a suspicious mole on the scalp or other body location, the vast majority turn out to be benign, because the incidence of melanoma is rare, especially before puberty.

“Only 1%-2% of all melanomas in the world are in children, so most of my job is to provide reassurance,” Dr. Piggott, a pediatric dermatologist at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “Few pediatric studies exist. Why? Because children are excluded from most melanoma clinical trials. Our management is based mainly on adult National Comprehensive Cancer Network guidelines.”

Doug Brunk/MDedge News

To help parents identify melanoma, clinicians typically recommend the “ABCDE” rule, for Asymmetry, Border irregularity, Color variation (especially dark or multiple colors), Diameter greater than 6 mm, and Evolving (is it changing, bleeding or painful?).

While Dr. Piggott considers the standard ABCDE rules as important – especially in older children and teenagers – researchers led by Kelly M. Cordoro, MD, professor of dermatology at the University of California, San Francisco, proposed a modified ABCD criteria based on evaluating a cohort of 60 children who were diagnosed with melanoma and 10 who were diagnosed with ambiguous melanocytic tumors treated as melanoma before age 20 years at UCSF from 1984 to 2009.

The researchers divided patients into two groups: those aged 0-10 years (19; group A) and those aged 11-19 years (51; group B), and found that 60% of children in group A and 40% of those in group B did not present with conventional ABCDE criteria for children. Of the 60 melanoma patients, 10 died. Of these, 9 were older than age 10, and 70% had amelanotic lesions. Based on their analysis of clinical, histopathologic, and outcomes data, Dr. Cordoro and colleagues proposed additional ABCD criteria in which A stands for stands Amelanotic; B for Bleeding or Bump; C for Color uniformity, and D for De novo or any Diameter.

“This doesn’t mean you throw the old ABCDE criteria out the window,” Dr. Piggott said. “It means that you use this modified criteria in conjunction with the conventional ABCDE rules.”

Risk factors for melanoma in children are like those in adults, and include a family history of melanoma, large/giant congenital nevi, the presence of many atypical appearing nevi, having Fitzpatrick skin types I or II, a history of blistering sunburns, and the presence of genetic anomalies such as xeroderma pigmentosum.

According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program, melanoma incidence increased in all individuals in the United States aged 0-19 years from 1973 to 2009. Key risk factors included White race, female sex, and living in a SEER registry categorized as low UVB exposure. Over the study period, boys experienced increased incidence rates of melanoma on the face and trunk, while girls experienced increased incidence rates of melanoma on the lower limbs and hip.

More recently, researchers extracted data from 988,103 cases of invasive melanoma in the 2001-2015 SEER database to determine the age-specific incidence of melanoma in the United States. In 2015, 83,362 cases of invasive melanoma were reported for all ages. Of these, only 67 cases were younger than age 10, while 251 were between the ages of 10 and 19 and 1,973 were young adults between the ages of 20 and 29.

In other findings, between 2006 and 2015, the overall incidence of invasive melanoma for all ages increased from 200 million to 229 cases per million person-years. “However, there were statistically significant decreases in melanoma incidence for individuals aged 10-19 years and for those aged 10-29 years,” said Dr. Piggott, who was not involved with the study. “The hypothesis is that public health efforts encouraging against sun exposure and tanning bed use may be influencing melanoma incidence in younger populations. What is interesting, though, is that young adult women have twice the melanoma risk as young adult men.”

In a separate study, researchers prospectively followed 60 melanoma-prone families for up to 40 years to evaluate the risk of pediatric melanoma in those with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. Regardless of their CDKN2A status, the percentage of pediatric melanoma cases was 6- to 28-fold higher among melanoma-prone families, compared with the general population. In addition, families who were CDKN2A positive had a significantly higher rate of pediatric melanoma cases compared with those who were CDKN2A negative (11.1% vs. 2.5%; P = .004).

As for treating pediatric melanoma, the standard of care is similar to that for adults: usually wide local surgical excision of the primary lesion, depending on depth. Clinicians typically follow adult parameters for sentinel lymph node biopsy, such as lesion depth and ulceration.

“We know that a positive sentinel node does have prognostic value, but there is great debate on whether to do a lymph node dissection if the sentinel lymph node is positive,” Dr. Piggott said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “This is determined on a case-by-case basis. We consider factors such as, are the nodes palpable? Is there evidence on ultrasound? But there are no formal guidelines.”

Limited studies of systemic therapy in children exist because this population is excluded from most melanoma clinical trials. “In the past, interferon was sometimes used,” she said. “But in recent years, as with adults, we have started to use targeted immunologic therapy. This is usually managed by a tertiary academic oncology center.”

The chance of surviving pediatric melanoma is good if caught early. As in adults, the stage correlates strongly with survival, and distant metastases carry a poor prognosis.

In 2020, researchers published a retrospective, multicenter review of 38 cases of fatal pediatric melanoma between 1994 and 2017. The analysis was limited to individuals 20 years of age and younger who were cared for at 12 academic medical centers. Of the 38 patients, 42% were male, 58% were female, and 57% were White. In addition, 19% were Hispanic, “which is a larger percentage than fatalities in adult [Hispanic] populations with melanoma,” said Dr. Piggott, who was not involved in the study.

The mean age at diagnosis was 12.7 years, the mean age at death was 15.6 , and the mean survival time after diagnosis was about 35 months. Of the 16 cases with known identifiable subtypes, 50% were nodular, 31% were superficial spreading, and 19% were spitzoid melanoma. In addition, one-quarter of melanomas arose in association with congenital melanocytic nevi.

“The good news is that there are only 38 total cases of fatal pediatric melanoma between 12 academic centers over a 23-year period,” Dr. Piggott said. “Thanks goodness the number is that low.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO – When parents bring their children to Caroline Piggott, MD, to evaluate a suspicious mole on the scalp or other body location, the vast majority turn out to be benign, because the incidence of melanoma is rare, especially before puberty.

“Only 1%-2% of all melanomas in the world are in children, so most of my job is to provide reassurance,” Dr. Piggott, a pediatric dermatologist at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “Few pediatric studies exist. Why? Because children are excluded from most melanoma clinical trials. Our management is based mainly on adult National Comprehensive Cancer Network guidelines.”

Doug Brunk/MDedge News

To help parents identify melanoma, clinicians typically recommend the “ABCDE” rule, for Asymmetry, Border irregularity, Color variation (especially dark or multiple colors), Diameter greater than 6 mm, and Evolving (is it changing, bleeding or painful?).

While Dr. Piggott considers the standard ABCDE rules as important – especially in older children and teenagers – researchers led by Kelly M. Cordoro, MD, professor of dermatology at the University of California, San Francisco, proposed a modified ABCD criteria based on evaluating a cohort of 60 children who were diagnosed with melanoma and 10 who were diagnosed with ambiguous melanocytic tumors treated as melanoma before age 20 years at UCSF from 1984 to 2009.

The researchers divided patients into two groups: those aged 0-10 years (19; group A) and those aged 11-19 years (51; group B), and found that 60% of children in group A and 40% of those in group B did not present with conventional ABCDE criteria for children. Of the 60 melanoma patients, 10 died. Of these, 9 were older than age 10, and 70% had amelanotic lesions. Based on their analysis of clinical, histopathologic, and outcomes data, Dr. Cordoro and colleagues proposed additional ABCD criteria in which A stands for stands Amelanotic; B for Bleeding or Bump; C for Color uniformity, and D for De novo or any Diameter.

“This doesn’t mean you throw the old ABCDE criteria out the window,” Dr. Piggott said. “It means that you use this modified criteria in conjunction with the conventional ABCDE rules.”

Risk factors for melanoma in children are like those in adults, and include a family history of melanoma, large/giant congenital nevi, the presence of many atypical appearing nevi, having Fitzpatrick skin types I or II, a history of blistering sunburns, and the presence of genetic anomalies such as xeroderma pigmentosum.

According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program, melanoma incidence increased in all individuals in the United States aged 0-19 years from 1973 to 2009. Key risk factors included White race, female sex, and living in a SEER registry categorized as low UVB exposure. Over the study period, boys experienced increased incidence rates of melanoma on the face and trunk, while girls experienced increased incidence rates of melanoma on the lower limbs and hip.

More recently, researchers extracted data from 988,103 cases of invasive melanoma in the 2001-2015 SEER database to determine the age-specific incidence of melanoma in the United States. In 2015, 83,362 cases of invasive melanoma were reported for all ages. Of these, only 67 cases were younger than age 10, while 251 were between the ages of 10 and 19 and 1,973 were young adults between the ages of 20 and 29.

In other findings, between 2006 and 2015, the overall incidence of invasive melanoma for all ages increased from 200 million to 229 cases per million person-years. “However, there were statistically significant decreases in melanoma incidence for individuals aged 10-19 years and for those aged 10-29 years,” said Dr. Piggott, who was not involved with the study. “The hypothesis is that public health efforts encouraging against sun exposure and tanning bed use may be influencing melanoma incidence in younger populations. What is interesting, though, is that young adult women have twice the melanoma risk as young adult men.”

In a separate study, researchers prospectively followed 60 melanoma-prone families for up to 40 years to evaluate the risk of pediatric melanoma in those with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. Regardless of their CDKN2A status, the percentage of pediatric melanoma cases was 6- to 28-fold higher among melanoma-prone families, compared with the general population. In addition, families who were CDKN2A positive had a significantly higher rate of pediatric melanoma cases compared with those who were CDKN2A negative (11.1% vs. 2.5%; P = .004).

As for treating pediatric melanoma, the standard of care is similar to that for adults: usually wide local surgical excision of the primary lesion, depending on depth. Clinicians typically follow adult parameters for sentinel lymph node biopsy, such as lesion depth and ulceration.

“We know that a positive sentinel node does have prognostic value, but there is great debate on whether to do a lymph node dissection if the sentinel lymph node is positive,” Dr. Piggott said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “This is determined on a case-by-case basis. We consider factors such as, are the nodes palpable? Is there evidence on ultrasound? But there are no formal guidelines.”

Limited studies of systemic therapy in children exist because this population is excluded from most melanoma clinical trials. “In the past, interferon was sometimes used,” she said. “But in recent years, as with adults, we have started to use targeted immunologic therapy. This is usually managed by a tertiary academic oncology center.”

The chance of surviving pediatric melanoma is good if caught early. As in adults, the stage correlates strongly with survival, and distant metastases carry a poor prognosis.

In 2020, researchers published a retrospective, multicenter review of 38 cases of fatal pediatric melanoma between 1994 and 2017. The analysis was limited to individuals 20 years of age and younger who were cared for at 12 academic medical centers. Of the 38 patients, 42% were male, 58% were female, and 57% were White. In addition, 19% were Hispanic, “which is a larger percentage than fatalities in adult [Hispanic] populations with melanoma,” said Dr. Piggott, who was not involved in the study.

The mean age at diagnosis was 12.7 years, the mean age at death was 15.6 , and the mean survival time after diagnosis was about 35 months. Of the 16 cases with known identifiable subtypes, 50% were nodular, 31% were superficial spreading, and 19% were spitzoid melanoma. In addition, one-quarter of melanomas arose in association with congenital melanocytic nevi.

“The good news is that there are only 38 total cases of fatal pediatric melanoma between 12 academic centers over a 23-year period,” Dr. Piggott said. “Thanks goodness the number is that low.”

Dr. Piggott reported having no relevant disclosures.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

This linear pattern of hyper-pigmented, often verrucous tissue oriented along Blaschko skin lines is typical for linear epidermal nevi (LEN). In some cases, lesions are not in a linear pattern and are actually in more of a localized or whorled pattern (called epidermal nevi).

LEN are usually present at birth, as in this individual. They are frequently seen on the head and neck region and are often asymptomatic. LEN are considered a birthmark that develops because of a genetic abnormality that typically affects keratinocytes. This genetic mutation only affects a portion of the body (mosaicism) without affecting the overall genetics of the individual. This is important to note because LEN do not typically have a hereditary component or implications for offspring. While usually asymptomatic and localized, LEN can be associated with extracutaneous and neurologic difficulties. In these situations, it is called epidermal nevus syndrome, and is more common if the LEN occur on the face or head.¹

Since LEN are usually asymptomatic, treatment is not required unless the lesions affect the function of adjacent structures, such as the eyes, lips, or nose. Due to their frequent presence on the face or other visible areas, some patients may choose to get these lesions treated for cosmetic purposes. In the past, full-thickness excision was recommended. Topical medications are ineffective, and superficial shave excision usually leads to recurrence. More recently, destructive laser treatments have been used, with success, to reduce the appearance of the lesions.²

This patient was not concerned about the appearance of the asymptomatic lesions and chose not to have any treatment.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This linear pattern of hyper-pigmented, often verrucous tissue oriented along Blaschko skin lines is typical for linear epidermal nevi (LEN). In some cases, lesions are not in a linear pattern and are actually in more of a localized or whorled pattern (called epidermal nevi).

LEN are usually present at birth, as in this individual. They are frequently seen on the head and neck region and are often asymptomatic. LEN are considered a birthmark that develops because of a genetic abnormality that typically affects keratinocytes. This genetic mutation only affects a portion of the body (mosaicism) without affecting the overall genetics of the individual. This is important to note because LEN do not typically have a hereditary component or implications for offspring. While usually asymptomatic and localized, LEN can be associated with extracutaneous and neurologic difficulties. In these situations, it is called epidermal nevus syndrome, and is more common if the LEN occur on the face or head.¹

Since LEN are usually asymptomatic, treatment is not required unless the lesions affect the function of adjacent structures, such as the eyes, lips, or nose. Due to their frequent presence on the face or other visible areas, some patients may choose to get these lesions treated for cosmetic purposes. In the past, full-thickness excision was recommended. Topical medications are ineffective, and superficial shave excision usually leads to recurrence. More recently, destructive laser treatments have been used, with success, to reduce the appearance of the lesions.²

This patient was not concerned about the appearance of the asymptomatic lesions and chose not to have any treatment.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This linear pattern of hyper-pigmented, often verrucous tissue oriented along Blaschko skin lines is typical for linear epidermal nevi (LEN). In some cases, lesions are not in a linear pattern and are actually in more of a localized or whorled pattern (called epidermal nevi).

LEN are usually present at birth, as in this individual. They are frequently seen on the head and neck region and are often asymptomatic. LEN are considered a birthmark that develops because of a genetic abnormality that typically affects keratinocytes. This genetic mutation only affects a portion of the body (mosaicism) without affecting the overall genetics of the individual. This is important to note because LEN do not typically have a hereditary component or implications for offspring. While usually asymptomatic and localized, LEN can be associated with extracutaneous and neurologic difficulties. In these situations, it is called epidermal nevus syndrome, and is more common if the LEN occur on the face or head.¹

Since LEN are usually asymptomatic, treatment is not required unless the lesions affect the function of adjacent structures, such as the eyes, lips, or nose. Due to their frequent presence on the face or other visible areas, some patients may choose to get these lesions treated for cosmetic purposes. In the past, full-thickness excision was recommended. Topical medications are ineffective, and superficial shave excision usually leads to recurrence. More recently, destructive laser treatments have been used, with success, to reduce the appearance of the lesions.²

This patient was not concerned about the appearance of the asymptomatic lesions and chose not to have any treatment.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Friday, Feb. 10, 2023, marked the first time a patient told me they had used ChatGPT to answer a medical question. I’ve been reluctant to write about this super-buzzy new AI chatbot, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.

It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:

Oh gentle healer of skin so fair,
Your touch is soft and hands so rare,
With your skills and gentle care,
You make my heart skip with a flare.

Not good enough to send to my wife. But not bad.

If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.

I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?

Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.

Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:

“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”

I’m not sure I could have said it better myself.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Friday, Feb. 10, 2023, marked the first time a patient told me they had used ChatGPT to answer a medical question. I’ve been reluctant to write about this super-buzzy new AI chatbot, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.

It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:

Oh gentle healer of skin so fair,
Your touch is soft and hands so rare,
With your skills and gentle care,
You make my heart skip with a flare.

Not good enough to send to my wife. But not bad.

If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.

I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?

Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.

Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:

“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”

I’m not sure I could have said it better myself.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Friday, Feb. 10, 2023, marked the first time a patient told me they had used ChatGPT to answer a medical question. I’ve been reluctant to write about this super-buzzy new AI chatbot, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.

It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:

Oh gentle healer of skin so fair,
Your touch is soft and hands so rare,
With your skills and gentle care,
You make my heart skip with a flare.

Not good enough to send to my wife. But not bad.

If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.

I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?

Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.

Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:

“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”

I’m not sure I could have said it better myself.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.

The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.

Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.

Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.

The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”

Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.

Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”

Mr. Driskell and Dr. Thorpe reported no relevant financial relationships. 

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

Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.

The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.

Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.

Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.

The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”

Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.

Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”

Mr. Driskell and Dr. Thorpe reported no relevant financial relationships. 

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

Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.

The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.

Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.

Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.

The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”

Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.

Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”

Mr. Driskell and Dr. Thorpe reported no relevant financial relationships. 

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

When administered subcutaneously every 2 weeks, secukinumab was effective at improving signs and symptoms of moderate to severe hidradenitis suppurativa (HS) in adults up to 52 weeks, results from two pivotal phase 3 clinical trials showed.

The findings build on week 16 data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety, and tolerability of the interleukin-17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS, and were presented at the 2022 annual congress of the European Academy of Dermatology and Venereology. In those studies, at 16 weeks, 42%-46% of patients achieved an HS Clinical Response (HiSCR) – the primary outcome measure in both trials. For the most recent analysis, which was published in The Lancet, investigators found that, at 52 weeks, 56.4% of patients in SUNSHINE and 65% of patients in SUNRISE who received secukinumab 300 mg every 2 weeks achieved a HiSCR, compared with 56.3% of patients in SUNSHINE and 62.2% of patients in SUNRISE who received secukinumab 300 mg every 4 weeks.

“This is great news for people with HS: it improves our knowledge about how to best treat patients today and leads us to new areas that will help us treat them even better in the future,” Alexa B. Kimball, MD, MPH, the lead investigator for both trials, said in an interview. “Dermatologists have been using biologics for decades. This data provides clinicians with information they can use to easily expand their HS management repertoire to include secukinumab.”

To date, the tumor necrosis factor inhibitor adalimumab is the only approved biologic therapy approved for the treatment of moderate-to-severe HS, in people aged 12 years and older.

The two trials were conducted in 40 countries, with SUNSHINE enrolling 541 patients, and SUNRISE enrolling 543. Patients in each study were randomized to one of three experimental arms: secukinumab 300 mg every 2 weeks after five weekly loading doses; secukinumab 300 mg every 4 weeks after five weekly loading doses; placebo dose every 2 weeks after five weekly placebo doses. The mean age was 37 years, about 55% were female, and about 76% were White (about 9% were Black and about 10% were Asian). Dr. Kimball, investigator at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, Boston, and coauthors observed that the group that received secukinumab every 4 weeks did not meet the primary endpoint in the SUNSHINE trial, but it was met in the SUNRISE trial. “Research and subgroup analyses are required and might improve our understanding of the effect of patient characteristics on treatment response and further refine the dosing recommendations for different populations,” they wrote.

In a pooled analysis, 55.2% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 2 weeks had a reduction in pain as measured by the Patient’s Global Assessment of Skin Pain Numeric Rating Scale, compared with 53% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 4 weeks. The most common adverse events up to week 16 in both trials were headache, nasopharyngitis, and hidradenitis; no deaths occurred.

“One limitation of most studies in HS is that the placebo-controlled period is short, so the data obtained after that time is harder to interpret,” Dr. Kimball said in an interview. “In my experience, optimizing treatment can take almost a year and I hope we will see longer controlled periods in future studies.” Another limitation of the studies she acknowledged was a modest imbalance with respect to disease severity between the treatment groups at baseline. “It was a little surprising that some imbalances in the characteristics of randomized subjects in different arms of the study impacted efficacy levels,” she said. “We’ll need to continue to identify how to match patients and dosing regimens to get the best results.”

According to a press release from Novartis, trial results have been submitted to regulatory authorities in Europe and the United States, and decisions are expected in 2023. If approved, secukinumab will be the first and only IL-17 inhibitor for the treatment of moderate to severe HS.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, described HS as “an extraordinarily disabling, painful, deforming condition for which we only have one [Food and Drug Administration]–approved systemic therapy, requiring us to wear our ‘off-label bandit’ name tags proudly to tackle therapeutic challenges.

“Anecdotally,” he said, “we dabble with off-label biologics indicated for psoriasis in this setting, though limitations exist ranging from lack of large-scale clinical data to the recurring theme that psoriasis dosing typically doesn’t cut it, making access to said medications even more difficult. Investigators in this study addresses both gaps very effectively, and I for one welcome the implications and hopeful regulatory impact with open arms.”

The study was funded by Novartis. Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.

When administered subcutaneously every 2 weeks, secukinumab was effective at improving signs and symptoms of moderate to severe hidradenitis suppurativa (HS) in adults up to 52 weeks, results from two pivotal phase 3 clinical trials showed.

The findings build on week 16 data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety, and tolerability of the interleukin-17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS, and were presented at the 2022 annual congress of the European Academy of Dermatology and Venereology. In those studies, at 16 weeks, 42%-46% of patients achieved an HS Clinical Response (HiSCR) – the primary outcome measure in both trials. For the most recent analysis, which was published in The Lancet, investigators found that, at 52 weeks, 56.4% of patients in SUNSHINE and 65% of patients in SUNRISE who received secukinumab 300 mg every 2 weeks achieved a HiSCR, compared with 56.3% of patients in SUNSHINE and 62.2% of patients in SUNRISE who received secukinumab 300 mg every 4 weeks.

“This is great news for people with HS: it improves our knowledge about how to best treat patients today and leads us to new areas that will help us treat them even better in the future,” Alexa B. Kimball, MD, MPH, the lead investigator for both trials, said in an interview. “Dermatologists have been using biologics for decades. This data provides clinicians with information they can use to easily expand their HS management repertoire to include secukinumab.”

To date, the tumor necrosis factor inhibitor adalimumab is the only approved biologic therapy approved for the treatment of moderate-to-severe HS, in people aged 12 years and older.

The two trials were conducted in 40 countries, with SUNSHINE enrolling 541 patients, and SUNRISE enrolling 543. Patients in each study were randomized to one of three experimental arms: secukinumab 300 mg every 2 weeks after five weekly loading doses; secukinumab 300 mg every 4 weeks after five weekly loading doses; placebo dose every 2 weeks after five weekly placebo doses. The mean age was 37 years, about 55% were female, and about 76% were White (about 9% were Black and about 10% were Asian). Dr. Kimball, investigator at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, Boston, and coauthors observed that the group that received secukinumab every 4 weeks did not meet the primary endpoint in the SUNSHINE trial, but it was met in the SUNRISE trial. “Research and subgroup analyses are required and might improve our understanding of the effect of patient characteristics on treatment response and further refine the dosing recommendations for different populations,” they wrote.

In a pooled analysis, 55.2% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 2 weeks had a reduction in pain as measured by the Patient’s Global Assessment of Skin Pain Numeric Rating Scale, compared with 53% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 4 weeks. The most common adverse events up to week 16 in both trials were headache, nasopharyngitis, and hidradenitis; no deaths occurred.

“One limitation of most studies in HS is that the placebo-controlled period is short, so the data obtained after that time is harder to interpret,” Dr. Kimball said in an interview. “In my experience, optimizing treatment can take almost a year and I hope we will see longer controlled periods in future studies.” Another limitation of the studies she acknowledged was a modest imbalance with respect to disease severity between the treatment groups at baseline. “It was a little surprising that some imbalances in the characteristics of randomized subjects in different arms of the study impacted efficacy levels,” she said. “We’ll need to continue to identify how to match patients and dosing regimens to get the best results.”

According to a press release from Novartis, trial results have been submitted to regulatory authorities in Europe and the United States, and decisions are expected in 2023. If approved, secukinumab will be the first and only IL-17 inhibitor for the treatment of moderate to severe HS.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, described HS as “an extraordinarily disabling, painful, deforming condition for which we only have one [Food and Drug Administration]–approved systemic therapy, requiring us to wear our ‘off-label bandit’ name tags proudly to tackle therapeutic challenges.

“Anecdotally,” he said, “we dabble with off-label biologics indicated for psoriasis in this setting, though limitations exist ranging from lack of large-scale clinical data to the recurring theme that psoriasis dosing typically doesn’t cut it, making access to said medications even more difficult. Investigators in this study addresses both gaps very effectively, and I for one welcome the implications and hopeful regulatory impact with open arms.”

The study was funded by Novartis. Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.

When administered subcutaneously every 2 weeks, secukinumab was effective at improving signs and symptoms of moderate to severe hidradenitis suppurativa (HS) in adults up to 52 weeks, results from two pivotal phase 3 clinical trials showed.

The findings build on week 16 data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety, and tolerability of the interleukin-17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS, and were presented at the 2022 annual congress of the European Academy of Dermatology and Venereology. In those studies, at 16 weeks, 42%-46% of patients achieved an HS Clinical Response (HiSCR) – the primary outcome measure in both trials. For the most recent analysis, which was published in The Lancet, investigators found that, at 52 weeks, 56.4% of patients in SUNSHINE and 65% of patients in SUNRISE who received secukinumab 300 mg every 2 weeks achieved a HiSCR, compared with 56.3% of patients in SUNSHINE and 62.2% of patients in SUNRISE who received secukinumab 300 mg every 4 weeks.

“This is great news for people with HS: it improves our knowledge about how to best treat patients today and leads us to new areas that will help us treat them even better in the future,” Alexa B. Kimball, MD, MPH, the lead investigator for both trials, said in an interview. “Dermatologists have been using biologics for decades. This data provides clinicians with information they can use to easily expand their HS management repertoire to include secukinumab.”

To date, the tumor necrosis factor inhibitor adalimumab is the only approved biologic therapy approved for the treatment of moderate-to-severe HS, in people aged 12 years and older.

The two trials were conducted in 40 countries, with SUNSHINE enrolling 541 patients, and SUNRISE enrolling 543. Patients in each study were randomized to one of three experimental arms: secukinumab 300 mg every 2 weeks after five weekly loading doses; secukinumab 300 mg every 4 weeks after five weekly loading doses; placebo dose every 2 weeks after five weekly placebo doses. The mean age was 37 years, about 55% were female, and about 76% were White (about 9% were Black and about 10% were Asian). Dr. Kimball, investigator at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, Boston, and coauthors observed that the group that received secukinumab every 4 weeks did not meet the primary endpoint in the SUNSHINE trial, but it was met in the SUNRISE trial. “Research and subgroup analyses are required and might improve our understanding of the effect of patient characteristics on treatment response and further refine the dosing recommendations for different populations,” they wrote.

In a pooled analysis, 55.2% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 2 weeks had a reduction in pain as measured by the Patient’s Global Assessment of Skin Pain Numeric Rating Scale, compared with 53% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 4 weeks. The most common adverse events up to week 16 in both trials were headache, nasopharyngitis, and hidradenitis; no deaths occurred.

“One limitation of most studies in HS is that the placebo-controlled period is short, so the data obtained after that time is harder to interpret,” Dr. Kimball said in an interview. “In my experience, optimizing treatment can take almost a year and I hope we will see longer controlled periods in future studies.” Another limitation of the studies she acknowledged was a modest imbalance with respect to disease severity between the treatment groups at baseline. “It was a little surprising that some imbalances in the characteristics of randomized subjects in different arms of the study impacted efficacy levels,” she said. “We’ll need to continue to identify how to match patients and dosing regimens to get the best results.”

According to a press release from Novartis, trial results have been submitted to regulatory authorities in Europe and the United States, and decisions are expected in 2023. If approved, secukinumab will be the first and only IL-17 inhibitor for the treatment of moderate to severe HS.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, described HS as “an extraordinarily disabling, painful, deforming condition for which we only have one [Food and Drug Administration]–approved systemic therapy, requiring us to wear our ‘off-label bandit’ name tags proudly to tackle therapeutic challenges.

“Anecdotally,” he said, “we dabble with off-label biologics indicated for psoriasis in this setting, though limitations exist ranging from lack of large-scale clinical data to the recurring theme that psoriasis dosing typically doesn’t cut it, making access to said medications even more difficult. Investigators in this study addresses both gaps very effectively, and I for one welcome the implications and hopeful regulatory impact with open arms.”

The study was funded by Novartis. Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.