For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

LAS VEGAS – Interventional cardiologists who used fractional flow reserve to assess coronary lesions with an uncertain hemodynamic impact by angiography alone changed their initial therapeutic decision based on angiography for 35% of patients, and for 30% of all lesions examined in a real-world registry with more than 2,200 patients enrolled at 70 worldwide centers.

Mitchel L. Zoler/MDedge News

“Use of fractional flow reserve in contemporary, real-world, global clinical practice changed treatment plans for more than one-third of all comers,” including both patients with stable coronary artery disease and those with acute coronary syndrome, Erick Schampaert, MD, said at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The impact of fractional flow reserve (FFR) was greatest when operators used it to assess nonculprit lesions among the 31% of the 2,217 total patients enrolled who presented with acute coronary syndrome. In this subgroup, FFR changed the treatment plan for nonculprit lesions that had been based on angiography and clinical status for 36% of these lesions. The changes included an increase in lesions identified to receive medical management, rising from 53% of the nonculprit lesions before FFR to 65% after, while treatment with percutaneous coronary intervention (PCI) fell from 37% of nonculprit lesions before FFR to 28% after, with the remaining lesions designated for coronary artery bypass grafting. Among patients with stable coronary disease the angiography-based treatment decision changed for 28% of nonculprit lesions after FFR.

“These results may provide support to increase use of FFR,” said Dr. Schampaert, an interventional cardiologist and head of cardiology at Hôpital du Sacré-Cœur in Montreal. The analysis “was an attempt to see the current impact of FFR at places where its use is established,” when it’s routinely used to assess the need to treat nonculprit lesions with an uncertain impact on blood flow through a coronary artery. Dr. Schampaert estimated that about one-quarter of patients who present for angiography have nonculprit lesions that leave operators uncertain about their hemodynamic significance after angiography and are candidates for FFR assessment.

The findings “are a call to do more FFR,” agreed M. Chadi Alraies, MD, an interventional cardiologist at the Detroit Medical Center Heart Hospital. “We are underusing FFR and overstenting people, and that worsens outcomes. We don’t do enough FFR,” Dr. Alraies commented.

“We’ve known for some time that angiography alone can lead to overtreatment,” commented Philippe Généreux, MD, an interventional cardiologist at Morristown (N.J.) Medical Center. “With FFR, physiology is the key to optimizing outcomes.”

The PRESSUREwire study included 2,217 consecutive patients who underwent FFR assessment at 70 centers in 15 countries during October 2016–February 2018. The only exclusions were patients with extremely tortuous or calcified arteries or patients with a bypass graft to the target vessel. Enrolled patients averaged 65 years of age, and three-quarters were men; 63% had stable coronary disease, 31% had acute coronary syndrome, and the remainder had silent ischemia documented by noninvasive testing. A stenosis of 50%-69% occluded 54% of the tested coronaries; 24% had a 70%-90% occlusion; 20% had an occlusion of less than 50%; and the remaining patients had an occlusion of more than 90%.

Mitchel L. Zoler/MDedge News

While the overall percentage of patients whose treatment plan changed following FFR assessment shifted moderately, the changes within each treatment category were more striking. For example, among the 62% of all patients initially designated for medical management based on angiography, the FFR findings changed the management plan to PCI in 19% of this subgroup. Conversely, among the 33% of all patients initially designated for PCI based on angiography, 52% instead received medical management based only on their FFR results. Because shifts in treatment strategy following FFR had some patients go from medical management to PCI, and others went from PCI to medical, overall the percentage of patients who received medical management without immediate revascularization had just a modest up-tick, from 62% before FFR to 67% after, Dr. Schampaert said.

PRESSUREwire was funded by Abbott Vascular, a company that markets an FFR device. Dr. Schampaert has been a consultant to Abbott Vascular as well as AstraZeneca, Bayer, Medtronic, Volcano-Philips, Sanofi, and Servier. Dr. Alaries had no disclosures. Dr. Généreux has been a consultant to Abbott Vascular and to several other companies, and he has an equity interest in Saranas.

[email protected]

SOURCE: Schampaert E et al. SCAI 2019, Abstract.

LAS VEGAS – Interventional cardiologists who used fractional flow reserve to assess coronary lesions with an uncertain hemodynamic impact by angiography alone changed their initial therapeutic decision based on angiography for 35% of patients, and for 30% of all lesions examined in a real-world registry with more than 2,200 patients enrolled at 70 worldwide centers.

Mitchel L. Zoler/MDedge News

“Use of fractional flow reserve in contemporary, real-world, global clinical practice changed treatment plans for more than one-third of all comers,” including both patients with stable coronary artery disease and those with acute coronary syndrome, Erick Schampaert, MD, said at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The impact of fractional flow reserve (FFR) was greatest when operators used it to assess nonculprit lesions among the 31% of the 2,217 total patients enrolled who presented with acute coronary syndrome. In this subgroup, FFR changed the treatment plan for nonculprit lesions that had been based on angiography and clinical status for 36% of these lesions. The changes included an increase in lesions identified to receive medical management, rising from 53% of the nonculprit lesions before FFR to 65% after, while treatment with percutaneous coronary intervention (PCI) fell from 37% of nonculprit lesions before FFR to 28% after, with the remaining lesions designated for coronary artery bypass grafting. Among patients with stable coronary disease the angiography-based treatment decision changed for 28% of nonculprit lesions after FFR.

“These results may provide support to increase use of FFR,” said Dr. Schampaert, an interventional cardiologist and head of cardiology at Hôpital du Sacré-Cœur in Montreal. The analysis “was an attempt to see the current impact of FFR at places where its use is established,” when it’s routinely used to assess the need to treat nonculprit lesions with an uncertain impact on blood flow through a coronary artery. Dr. Schampaert estimated that about one-quarter of patients who present for angiography have nonculprit lesions that leave operators uncertain about their hemodynamic significance after angiography and are candidates for FFR assessment.

The findings “are a call to do more FFR,” agreed M. Chadi Alraies, MD, an interventional cardiologist at the Detroit Medical Center Heart Hospital. “We are underusing FFR and overstenting people, and that worsens outcomes. We don’t do enough FFR,” Dr. Alraies commented.

“We’ve known for some time that angiography alone can lead to overtreatment,” commented Philippe Généreux, MD, an interventional cardiologist at Morristown (N.J.) Medical Center. “With FFR, physiology is the key to optimizing outcomes.”

The PRESSUREwire study included 2,217 consecutive patients who underwent FFR assessment at 70 centers in 15 countries during October 2016–February 2018. The only exclusions were patients with extremely tortuous or calcified arteries or patients with a bypass graft to the target vessel. Enrolled patients averaged 65 years of age, and three-quarters were men; 63% had stable coronary disease, 31% had acute coronary syndrome, and the remainder had silent ischemia documented by noninvasive testing. A stenosis of 50%-69% occluded 54% of the tested coronaries; 24% had a 70%-90% occlusion; 20% had an occlusion of less than 50%; and the remaining patients had an occlusion of more than 90%.

Mitchel L. Zoler/MDedge News

While the overall percentage of patients whose treatment plan changed following FFR assessment shifted moderately, the changes within each treatment category were more striking. For example, among the 62% of all patients initially designated for medical management based on angiography, the FFR findings changed the management plan to PCI in 19% of this subgroup. Conversely, among the 33% of all patients initially designated for PCI based on angiography, 52% instead received medical management based only on their FFR results. Because shifts in treatment strategy following FFR had some patients go from medical management to PCI, and others went from PCI to medical, overall the percentage of patients who received medical management without immediate revascularization had just a modest up-tick, from 62% before FFR to 67% after, Dr. Schampaert said.

PRESSUREwire was funded by Abbott Vascular, a company that markets an FFR device. Dr. Schampaert has been a consultant to Abbott Vascular as well as AstraZeneca, Bayer, Medtronic, Volcano-Philips, Sanofi, and Servier. Dr. Alaries had no disclosures. Dr. Généreux has been a consultant to Abbott Vascular and to several other companies, and he has an equity interest in Saranas.

[email protected]

SOURCE: Schampaert E et al. SCAI 2019, Abstract.

LAS VEGAS – Interventional cardiologists who used fractional flow reserve to assess coronary lesions with an uncertain hemodynamic impact by angiography alone changed their initial therapeutic decision based on angiography for 35% of patients, and for 30% of all lesions examined in a real-world registry with more than 2,200 patients enrolled at 70 worldwide centers.

Mitchel L. Zoler/MDedge News

“Use of fractional flow reserve in contemporary, real-world, global clinical practice changed treatment plans for more than one-third of all comers,” including both patients with stable coronary artery disease and those with acute coronary syndrome, Erick Schampaert, MD, said at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The impact of fractional flow reserve (FFR) was greatest when operators used it to assess nonculprit lesions among the 31% of the 2,217 total patients enrolled who presented with acute coronary syndrome. In this subgroup, FFR changed the treatment plan for nonculprit lesions that had been based on angiography and clinical status for 36% of these lesions. The changes included an increase in lesions identified to receive medical management, rising from 53% of the nonculprit lesions before FFR to 65% after, while treatment with percutaneous coronary intervention (PCI) fell from 37% of nonculprit lesions before FFR to 28% after, with the remaining lesions designated for coronary artery bypass grafting. Among patients with stable coronary disease the angiography-based treatment decision changed for 28% of nonculprit lesions after FFR.

“These results may provide support to increase use of FFR,” said Dr. Schampaert, an interventional cardiologist and head of cardiology at Hôpital du Sacré-Cœur in Montreal. The analysis “was an attempt to see the current impact of FFR at places where its use is established,” when it’s routinely used to assess the need to treat nonculprit lesions with an uncertain impact on blood flow through a coronary artery. Dr. Schampaert estimated that about one-quarter of patients who present for angiography have nonculprit lesions that leave operators uncertain about their hemodynamic significance after angiography and are candidates for FFR assessment.

The findings “are a call to do more FFR,” agreed M. Chadi Alraies, MD, an interventional cardiologist at the Detroit Medical Center Heart Hospital. “We are underusing FFR and overstenting people, and that worsens outcomes. We don’t do enough FFR,” Dr. Alraies commented.

“We’ve known for some time that angiography alone can lead to overtreatment,” commented Philippe Généreux, MD, an interventional cardiologist at Morristown (N.J.) Medical Center. “With FFR, physiology is the key to optimizing outcomes.”

The PRESSUREwire study included 2,217 consecutive patients who underwent FFR assessment at 70 centers in 15 countries during October 2016–February 2018. The only exclusions were patients with extremely tortuous or calcified arteries or patients with a bypass graft to the target vessel. Enrolled patients averaged 65 years of age, and three-quarters were men; 63% had stable coronary disease, 31% had acute coronary syndrome, and the remainder had silent ischemia documented by noninvasive testing. A stenosis of 50%-69% occluded 54% of the tested coronaries; 24% had a 70%-90% occlusion; 20% had an occlusion of less than 50%; and the remaining patients had an occlusion of more than 90%.

Mitchel L. Zoler/MDedge News

While the overall percentage of patients whose treatment plan changed following FFR assessment shifted moderately, the changes within each treatment category were more striking. For example, among the 62% of all patients initially designated for medical management based on angiography, the FFR findings changed the management plan to PCI in 19% of this subgroup. Conversely, among the 33% of all patients initially designated for PCI based on angiography, 52% instead received medical management based only on their FFR results. Because shifts in treatment strategy following FFR had some patients go from medical management to PCI, and others went from PCI to medical, overall the percentage of patients who received medical management without immediate revascularization had just a modest up-tick, from 62% before FFR to 67% after, Dr. Schampaert said.

PRESSUREwire was funded by Abbott Vascular, a company that markets an FFR device. Dr. Schampaert has been a consultant to Abbott Vascular as well as AstraZeneca, Bayer, Medtronic, Volcano-Philips, Sanofi, and Servier. Dr. Alaries had no disclosures. Dr. Généreux has been a consultant to Abbott Vascular and to several other companies, and he has an equity interest in Saranas.

[email protected]

SOURCE: Schampaert E et al. SCAI 2019, Abstract.

LJUBLJANA, SLOVENIA – There is good news and bad news about human papillomavirus (HPV) vaccination as a means of preventing cervical cancer.

Bruce Jancin/MDedge News

The bad news is the HPV vaccines are projected to be in short supply, unable to meet global demand until at least 2024. The good news is that mounting evidence strongly suggests that one HPV dose may provide durable protection – in one study, for 11 years and counting – which would effectively double the existing supply, Aimee R. Kreimer, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

These data come from post hoc analyses of major phase 3 randomized controlled trials of bivalent HPV vaccine in Costa Rica and quadrivalent vaccine in India. However, these secondary analyses aren’t considered rock solid evidence because the subjects who got a single dose weren’t randomized to that strategy, they simply for one reason or another didn’t receive the recommended additional dose or doses.

“I don’t know if these studies are enough, so several studies have been launched over the past couple of years with an eye toward generating the quality of data that would be sufficient to motivate policy change, if in fact one dose is proven to be effective,” said Dr. Kreimer, a senior scientist at the National Cancer Institute in Bethesda, Md.

The first of these formal randomized, controlled trials – a delayed second-dose study in 9- to 11-year-old U.S. boys and girls – is due to be completed next year. Four other trials ongoing in Africa and Costa Rica, all in females, are expected to report findings in 2022-2025.

Dr. Kreimer is first author of a soon-to-be-published 11-year update from the phase 3 Costa Rica HPV Vaccine Trial, which was launched prior to licensure of the GlaxoSmithKline bivalent HPV vaccine. Previous analyses showed that at both 4 and 7 years of follow-up, a single dose of the vaccine was as effective as two or three in preventing infection with HPV types 16 and 18, which are covered by the vaccine.

“Now the research question has transitioned to, ‘Will one dose be sufficiently durable?’ she explained.

The answer from this study is yes. At 11 years since receipt of the bivalent HPV vaccine, there was no difference in terms of prevalent HPV 16/18 infection between the one-, two-, and three-dose groups. To address the issue of possible selection bias in this post hoc nonrandomized comparison, Dr. Kreimer and her coinvestigators looked at rates of infection with HPV 31 and 45, which aren’t covered by the vaccine. The rates were similar regardless of the number of vaccine doses received 11 years earlier, indicating women in all three dosing groups are at similar risk for acquiring HPV infection, thus bolstering the legitimacy of the conclusion that one dose provides effective long-term protection.

Intriguingly, HPV serum antibody levels in the single-dose group have remained stable for 11 years at a level that’s only about one-quarter of that associated with three doses of the vaccine, albeit an order of magnitude greater than the level induced by natural immunity.

“This really challenges the dogma of the HPV vaccine,” according to Dr. Kreimer. “It suggests that inferior [HPV] antibodies do not necessarily mean inferior protection.”

The explanation for this phenomenon appears to be that HPV subunit vaccine mimics the shell of authentic virions so well that the immune system sees it as dangerous and mounts long-term antibody production. Also, cervical infection by HPV is a relatively slow process, allowing time for vaccine-induced antibodies to interrupt it, she said.

In contrast to the encouraging findings from this post hoc analysis and another from a phase 3 trial of quadrivalent vaccine in India, numerous phase 4 vaccine effectiveness monitoring studies have shown markedly lower vaccine effectiveness for one dose of HPV vaccine. Dr. Kreimer cautioned that this is a flawed conclusion attributable to a methodologic artifact whereby the investigators have lumped together single-dose recipients who were 17 years old or more at the time with those who were younger.

“The problem is that many people who are aged 17-18 years already have HPV infection, so when they are vaccinated it shows up as a vaccine failure. That’s not correct. These are prophylactic HPV vaccines. They’re not meant to help clear an infection,” she noted.

Stepping back, Dr. Kreimer observed that cervical cancer “is really a story of inequality.” Indeed, 90% of cervical cancers occur in low-income countries, where HPV vaccination uptake remains very low even more than a decade after licensure. When modelers project out in the future, they estimate that at current HPV vaccination levels in Sub-Saharan Africa, which has the highest cervical cancer rates in the world, it would take more than 100 years to achieve the World Health Organization goal of eliminating the malignancy.

Asked by an audience member how low a single-dose vaccine effectiveness level she considers acceptable to help reach the goal of eliminating cervical cancer in developing countries, Dr. Kreimer cautioned against the tendency to let ‘perfect’ become the enemy of ‘good.’

“I’ll remind everyone that, in this moment, very few of the target girls in the lower– and upper-lower–income countries are getting any vaccination. So I don’t think it’s a question of whether we should be going from two to one dose, I think it’s really a question of, for those who are at zero doses, how do we get them one dose? And with the HPV vaccine, we’ve even seen suggestions of herd immunity if we have 50% uptake,” she replied.

Dr. Kreimer reported having no financial conflicts regarding her presentation.

[email protected]

LJUBLJANA, SLOVENIA – There is good news and bad news about human papillomavirus (HPV) vaccination as a means of preventing cervical cancer.

Bruce Jancin/MDedge News

The bad news is the HPV vaccines are projected to be in short supply, unable to meet global demand until at least 2024. The good news is that mounting evidence strongly suggests that one HPV dose may provide durable protection – in one study, for 11 years and counting – which would effectively double the existing supply, Aimee R. Kreimer, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

These data come from post hoc analyses of major phase 3 randomized controlled trials of bivalent HPV vaccine in Costa Rica and quadrivalent vaccine in India. However, these secondary analyses aren’t considered rock solid evidence because the subjects who got a single dose weren’t randomized to that strategy, they simply for one reason or another didn’t receive the recommended additional dose or doses.

“I don’t know if these studies are enough, so several studies have been launched over the past couple of years with an eye toward generating the quality of data that would be sufficient to motivate policy change, if in fact one dose is proven to be effective,” said Dr. Kreimer, a senior scientist at the National Cancer Institute in Bethesda, Md.

The first of these formal randomized, controlled trials – a delayed second-dose study in 9- to 11-year-old U.S. boys and girls – is due to be completed next year. Four other trials ongoing in Africa and Costa Rica, all in females, are expected to report findings in 2022-2025.

Dr. Kreimer is first author of a soon-to-be-published 11-year update from the phase 3 Costa Rica HPV Vaccine Trial, which was launched prior to licensure of the GlaxoSmithKline bivalent HPV vaccine. Previous analyses showed that at both 4 and 7 years of follow-up, a single dose of the vaccine was as effective as two or three in preventing infection with HPV types 16 and 18, which are covered by the vaccine.

“Now the research question has transitioned to, ‘Will one dose be sufficiently durable?’ she explained.

The answer from this study is yes. At 11 years since receipt of the bivalent HPV vaccine, there was no difference in terms of prevalent HPV 16/18 infection between the one-, two-, and three-dose groups. To address the issue of possible selection bias in this post hoc nonrandomized comparison, Dr. Kreimer and her coinvestigators looked at rates of infection with HPV 31 and 45, which aren’t covered by the vaccine. The rates were similar regardless of the number of vaccine doses received 11 years earlier, indicating women in all three dosing groups are at similar risk for acquiring HPV infection, thus bolstering the legitimacy of the conclusion that one dose provides effective long-term protection.

Intriguingly, HPV serum antibody levels in the single-dose group have remained stable for 11 years at a level that’s only about one-quarter of that associated with three doses of the vaccine, albeit an order of magnitude greater than the level induced by natural immunity.

“This really challenges the dogma of the HPV vaccine,” according to Dr. Kreimer. “It suggests that inferior [HPV] antibodies do not necessarily mean inferior protection.”

The explanation for this phenomenon appears to be that HPV subunit vaccine mimics the shell of authentic virions so well that the immune system sees it as dangerous and mounts long-term antibody production. Also, cervical infection by HPV is a relatively slow process, allowing time for vaccine-induced antibodies to interrupt it, she said.

In contrast to the encouraging findings from this post hoc analysis and another from a phase 3 trial of quadrivalent vaccine in India, numerous phase 4 vaccine effectiveness monitoring studies have shown markedly lower vaccine effectiveness for one dose of HPV vaccine. Dr. Kreimer cautioned that this is a flawed conclusion attributable to a methodologic artifact whereby the investigators have lumped together single-dose recipients who were 17 years old or more at the time with those who were younger.

“The problem is that many people who are aged 17-18 years already have HPV infection, so when they are vaccinated it shows up as a vaccine failure. That’s not correct. These are prophylactic HPV vaccines. They’re not meant to help clear an infection,” she noted.

Stepping back, Dr. Kreimer observed that cervical cancer “is really a story of inequality.” Indeed, 90% of cervical cancers occur in low-income countries, where HPV vaccination uptake remains very low even more than a decade after licensure. When modelers project out in the future, they estimate that at current HPV vaccination levels in Sub-Saharan Africa, which has the highest cervical cancer rates in the world, it would take more than 100 years to achieve the World Health Organization goal of eliminating the malignancy.

Asked by an audience member how low a single-dose vaccine effectiveness level she considers acceptable to help reach the goal of eliminating cervical cancer in developing countries, Dr. Kreimer cautioned against the tendency to let ‘perfect’ become the enemy of ‘good.’

“I’ll remind everyone that, in this moment, very few of the target girls in the lower– and upper-lower–income countries are getting any vaccination. So I don’t think it’s a question of whether we should be going from two to one dose, I think it’s really a question of, for those who are at zero doses, how do we get them one dose? And with the HPV vaccine, we’ve even seen suggestions of herd immunity if we have 50% uptake,” she replied.

Dr. Kreimer reported having no financial conflicts regarding her presentation.

[email protected]

LJUBLJANA, SLOVENIA – There is good news and bad news about human papillomavirus (HPV) vaccination as a means of preventing cervical cancer.

Bruce Jancin/MDedge News

The bad news is the HPV vaccines are projected to be in short supply, unable to meet global demand until at least 2024. The good news is that mounting evidence strongly suggests that one HPV dose may provide durable protection – in one study, for 11 years and counting – which would effectively double the existing supply, Aimee R. Kreimer, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

These data come from post hoc analyses of major phase 3 randomized controlled trials of bivalent HPV vaccine in Costa Rica and quadrivalent vaccine in India. However, these secondary analyses aren’t considered rock solid evidence because the subjects who got a single dose weren’t randomized to that strategy, they simply for one reason or another didn’t receive the recommended additional dose or doses.

“I don’t know if these studies are enough, so several studies have been launched over the past couple of years with an eye toward generating the quality of data that would be sufficient to motivate policy change, if in fact one dose is proven to be effective,” said Dr. Kreimer, a senior scientist at the National Cancer Institute in Bethesda, Md.

The first of these formal randomized, controlled trials – a delayed second-dose study in 9- to 11-year-old U.S. boys and girls – is due to be completed next year. Four other trials ongoing in Africa and Costa Rica, all in females, are expected to report findings in 2022-2025.

Dr. Kreimer is first author of a soon-to-be-published 11-year update from the phase 3 Costa Rica HPV Vaccine Trial, which was launched prior to licensure of the GlaxoSmithKline bivalent HPV vaccine. Previous analyses showed that at both 4 and 7 years of follow-up, a single dose of the vaccine was as effective as two or three in preventing infection with HPV types 16 and 18, which are covered by the vaccine.

“Now the research question has transitioned to, ‘Will one dose be sufficiently durable?’ she explained.

The answer from this study is yes. At 11 years since receipt of the bivalent HPV vaccine, there was no difference in terms of prevalent HPV 16/18 infection between the one-, two-, and three-dose groups. To address the issue of possible selection bias in this post hoc nonrandomized comparison, Dr. Kreimer and her coinvestigators looked at rates of infection with HPV 31 and 45, which aren’t covered by the vaccine. The rates were similar regardless of the number of vaccine doses received 11 years earlier, indicating women in all three dosing groups are at similar risk for acquiring HPV infection, thus bolstering the legitimacy of the conclusion that one dose provides effective long-term protection.

Intriguingly, HPV serum antibody levels in the single-dose group have remained stable for 11 years at a level that’s only about one-quarter of that associated with three doses of the vaccine, albeit an order of magnitude greater than the level induced by natural immunity.

“This really challenges the dogma of the HPV vaccine,” according to Dr. Kreimer. “It suggests that inferior [HPV] antibodies do not necessarily mean inferior protection.”

The explanation for this phenomenon appears to be that HPV subunit vaccine mimics the shell of authentic virions so well that the immune system sees it as dangerous and mounts long-term antibody production. Also, cervical infection by HPV is a relatively slow process, allowing time for vaccine-induced antibodies to interrupt it, she said.

In contrast to the encouraging findings from this post hoc analysis and another from a phase 3 trial of quadrivalent vaccine in India, numerous phase 4 vaccine effectiveness monitoring studies have shown markedly lower vaccine effectiveness for one dose of HPV vaccine. Dr. Kreimer cautioned that this is a flawed conclusion attributable to a methodologic artifact whereby the investigators have lumped together single-dose recipients who were 17 years old or more at the time with those who were younger.

“The problem is that many people who are aged 17-18 years already have HPV infection, so when they are vaccinated it shows up as a vaccine failure. That’s not correct. These are prophylactic HPV vaccines. They’re not meant to help clear an infection,” she noted.

Stepping back, Dr. Kreimer observed that cervical cancer “is really a story of inequality.” Indeed, 90% of cervical cancers occur in low-income countries, where HPV vaccination uptake remains very low even more than a decade after licensure. When modelers project out in the future, they estimate that at current HPV vaccination levels in Sub-Saharan Africa, which has the highest cervical cancer rates in the world, it would take more than 100 years to achieve the World Health Organization goal of eliminating the malignancy.

Asked by an audience member how low a single-dose vaccine effectiveness level she considers acceptable to help reach the goal of eliminating cervical cancer in developing countries, Dr. Kreimer cautioned against the tendency to let ‘perfect’ become the enemy of ‘good.’

“I’ll remind everyone that, in this moment, very few of the target girls in the lower– and upper-lower–income countries are getting any vaccination. So I don’t think it’s a question of whether we should be going from two to one dose, I think it’s really a question of, for those who are at zero doses, how do we get them one dose? And with the HPV vaccine, we’ve even seen suggestions of herd immunity if we have 50% uptake,” she replied.

Dr. Kreimer reported having no financial conflicts regarding her presentation.

[email protected]

As the rest of the industrialized world has seen a decline in maternal mortality, the United States has seen a substantial rise over the last 30 years (FIGURE).¹ It is estimated that more than 60% of these pregnancy-related deaths are preventable. Additionally, substantial disparities exist, with African-American women 3 to 4 times more likely to die of pregnancy-related complications than white women.¹

A good first step

The Preventing Maternal Deaths Act was passed by the 115th Congress and signed into law December 2018 in an effort to support and expand maternal mortality review committees (MMRCs) on a state level while allowing the Centers for Disease Control and Prevention (CDC) to further study disparities within maternal mortality. Although these efforts are a good first step to help reduce maternal mortality, more needs to be done to quell this growing epidemic.

We must now improve care access

One strategy to aid in decreasing maternal morbidity and mortality is to improve affordable access to medical care. Medicaid is the largest single payer of maternity care in the United States, covering 42.6% of births. Currently, in many states, Medicaid coverage only lasts until a woman is 60 days postpartum.² Although 31 states, including the District of Columbia, have adopted Medicaid expansion programs to allow women to extend coverage beyond those 60 days, offering these programs is not a federal law. In the 19 remaining states with no extension options, the vast majority of women will lose their Medicaid coverage just after they are 2 months postpartum and will have no alternative health insurance coverage.²

Why does this coverage cutoff matter? Pregnancy-related deaths are defined as up to 12 months postpartum. A report reviewing 9 MMRCs found that 38% of pregnancy-related deaths occurred while a woman was pregnant, 45% of deaths occurred within 42 days of delivery, and 18% from 43 days to 1 year after delivery.³ Additionally, nearly half of women with Medicaid do not come to their 6-week postpartum visit (for a variety of reasons), missing a critical opportunity to address health concerns.² Of the deaths that occurred in this later postpartum period, leading causes were cardiomyopathy (32%), mental health conditions (16%), and embolism (11%).³ Prevention and management of these conditions require regular follow-up with an ObGyn, as well as potentially from subspecialists in cardiology, psychiatry, hematology, and other subspecialties. Women not having access to affordable health care during the critical postpartum period greatly increases their risk of death or severe morbidity.

An important next step beyond the Preventing Maternal Deaths Act is to extend Medicaid coverage to 12 months postpartum for all women everywhere. MMRCs have concluded that extending coverage would ensure that “medical and behavioral health conditions [could be] managed and treated before becoming progressively severe.”³ This would presumably help decrease the risk of pregnancy-related death and address worsening morbidity. Additionally, the postpartum period is a well-established time of increased stress and can be an overwhelming and emotional time for many new mothers, especially for those with limited resources for childcare, transportation, stable housing, etc.⁶ Providing and ensuring ongoing medical care would substantially improve the lives and health of women and the health of their families.

We, as a country, need to make changes

Every step of the way, a woman faces challenges to safely and affordably access health care. Providing access to insurance coverage for 12 months postpartum can help to decrease our country’s rising maternal mortality and morbidity rates.

Take action

Congresswoman Robin Kelly (D-IL) and Senator Dick Durbin (D-IL) have introduced the MOMMA Act (H.R. 1897/S. 916) to help address the rising maternal mortality rate.

This Act would:

• Expand Medicaid coverage to 1 year postpartum.
• Work with the CDC to uniformly collect data to accurately assess maternal mortality and morbidity.
• Ensure the sharing of best practices of care across hospital systems.
• Focus on culturally-competent care to address implicit bias among health care workers.
• Support and expand the Alliance for Innovation on Maternal Health (AIM)—a data-driven initiative to implement safety protocols in hospitals across the country.

To call or contact your representative to co-sponsor this bill, click here. To review if your Congressperson is a co-sponsor, click here. To review if your Senator is a co-sponsor, click here.
 

As the rest of the industrialized world has seen a decline in maternal mortality, the United States has seen a substantial rise over the last 30 years (FIGURE).¹ It is estimated that more than 60% of these pregnancy-related deaths are preventable. Additionally, substantial disparities exist, with African-American women 3 to 4 times more likely to die of pregnancy-related complications than white women.¹

A good first step

The Preventing Maternal Deaths Act was passed by the 115th Congress and signed into law December 2018 in an effort to support and expand maternal mortality review committees (MMRCs) on a state level while allowing the Centers for Disease Control and Prevention (CDC) to further study disparities within maternal mortality. Although these efforts are a good first step to help reduce maternal mortality, more needs to be done to quell this growing epidemic.

We must now improve care access

One strategy to aid in decreasing maternal morbidity and mortality is to improve affordable access to medical care. Medicaid is the largest single payer of maternity care in the United States, covering 42.6% of births. Currently, in many states, Medicaid coverage only lasts until a woman is 60 days postpartum.² Although 31 states, including the District of Columbia, have adopted Medicaid expansion programs to allow women to extend coverage beyond those 60 days, offering these programs is not a federal law. In the 19 remaining states with no extension options, the vast majority of women will lose their Medicaid coverage just after they are 2 months postpartum and will have no alternative health insurance coverage.²

Why does this coverage cutoff matter? Pregnancy-related deaths are defined as up to 12 months postpartum. A report reviewing 9 MMRCs found that 38% of pregnancy-related deaths occurred while a woman was pregnant, 45% of deaths occurred within 42 days of delivery, and 18% from 43 days to 1 year after delivery.³ Additionally, nearly half of women with Medicaid do not come to their 6-week postpartum visit (for a variety of reasons), missing a critical opportunity to address health concerns.² Of the deaths that occurred in this later postpartum period, leading causes were cardiomyopathy (32%), mental health conditions (16%), and embolism (11%).³ Prevention and management of these conditions require regular follow-up with an ObGyn, as well as potentially from subspecialists in cardiology, psychiatry, hematology, and other subspecialties. Women not having access to affordable health care during the critical postpartum period greatly increases their risk of death or severe morbidity.

An important next step beyond the Preventing Maternal Deaths Act is to extend Medicaid coverage to 12 months postpartum for all women everywhere. MMRCs have concluded that extending coverage would ensure that “medical and behavioral health conditions [could be] managed and treated before becoming progressively severe.”³ This would presumably help decrease the risk of pregnancy-related death and address worsening morbidity. Additionally, the postpartum period is a well-established time of increased stress and can be an overwhelming and emotional time for many new mothers, especially for those with limited resources for childcare, transportation, stable housing, etc.⁶ Providing and ensuring ongoing medical care would substantially improve the lives and health of women and the health of their families.

We, as a country, need to make changes

Every step of the way, a woman faces challenges to safely and affordably access health care. Providing access to insurance coverage for 12 months postpartum can help to decrease our country’s rising maternal mortality and morbidity rates.

Take action

Congresswoman Robin Kelly (D-IL) and Senator Dick Durbin (D-IL) have introduced the MOMMA Act (H.R. 1897/S. 916) to help address the rising maternal mortality rate.

This Act would:

• Expand Medicaid coverage to 1 year postpartum.
• Work with the CDC to uniformly collect data to accurately assess maternal mortality and morbidity.
• Ensure the sharing of best practices of care across hospital systems.
• Focus on culturally-competent care to address implicit bias among health care workers.
• Support and expand the Alliance for Innovation on Maternal Health (AIM)—a data-driven initiative to implement safety protocols in hospitals across the country.

To call or contact your representative to co-sponsor this bill, click here. To review if your Congressperson is a co-sponsor, click here. To review if your Senator is a co-sponsor, click here.
 

As the rest of the industrialized world has seen a decline in maternal mortality, the United States has seen a substantial rise over the last 30 years (FIGURE).¹ It is estimated that more than 60% of these pregnancy-related deaths are preventable. Additionally, substantial disparities exist, with African-American women 3 to 4 times more likely to die of pregnancy-related complications than white women.¹

A good first step

The Preventing Maternal Deaths Act was passed by the 115th Congress and signed into law December 2018 in an effort to support and expand maternal mortality review committees (MMRCs) on a state level while allowing the Centers for Disease Control and Prevention (CDC) to further study disparities within maternal mortality. Although these efforts are a good first step to help reduce maternal mortality, more needs to be done to quell this growing epidemic.

We must now improve care access

One strategy to aid in decreasing maternal morbidity and mortality is to improve affordable access to medical care. Medicaid is the largest single payer of maternity care in the United States, covering 42.6% of births. Currently, in many states, Medicaid coverage only lasts until a woman is 60 days postpartum.² Although 31 states, including the District of Columbia, have adopted Medicaid expansion programs to allow women to extend coverage beyond those 60 days, offering these programs is not a federal law. In the 19 remaining states with no extension options, the vast majority of women will lose their Medicaid coverage just after they are 2 months postpartum and will have no alternative health insurance coverage.²

Why does this coverage cutoff matter? Pregnancy-related deaths are defined as up to 12 months postpartum. A report reviewing 9 MMRCs found that 38% of pregnancy-related deaths occurred while a woman was pregnant, 45% of deaths occurred within 42 days of delivery, and 18% from 43 days to 1 year after delivery.³ Additionally, nearly half of women with Medicaid do not come to their 6-week postpartum visit (for a variety of reasons), missing a critical opportunity to address health concerns.² Of the deaths that occurred in this later postpartum period, leading causes were cardiomyopathy (32%), mental health conditions (16%), and embolism (11%).³ Prevention and management of these conditions require regular follow-up with an ObGyn, as well as potentially from subspecialists in cardiology, psychiatry, hematology, and other subspecialties. Women not having access to affordable health care during the critical postpartum period greatly increases their risk of death or severe morbidity.

An important next step beyond the Preventing Maternal Deaths Act is to extend Medicaid coverage to 12 months postpartum for all women everywhere. MMRCs have concluded that extending coverage would ensure that “medical and behavioral health conditions [could be] managed and treated before becoming progressively severe.”³ This would presumably help decrease the risk of pregnancy-related death and address worsening morbidity. Additionally, the postpartum period is a well-established time of increased stress and can be an overwhelming and emotional time for many new mothers, especially for those with limited resources for childcare, transportation, stable housing, etc.⁶ Providing and ensuring ongoing medical care would substantially improve the lives and health of women and the health of their families.

We, as a country, need to make changes

Every step of the way, a woman faces challenges to safely and affordably access health care. Providing access to insurance coverage for 12 months postpartum can help to decrease our country’s rising maternal mortality and morbidity rates.

Take action

Congresswoman Robin Kelly (D-IL) and Senator Dick Durbin (D-IL) have introduced the MOMMA Act (H.R. 1897/S. 916) to help address the rising maternal mortality rate.

This Act would:

• Expand Medicaid coverage to 1 year postpartum.
• Work with the CDC to uniformly collect data to accurately assess maternal mortality and morbidity.
• Ensure the sharing of best practices of care across hospital systems.
• Focus on culturally-competent care to address implicit bias among health care workers.
• Support and expand the Alliance for Innovation on Maternal Health (AIM)—a data-driven initiative to implement safety protocols in hospitals across the country.

To call or contact your representative to co-sponsor this bill, click here. To review if your Congressperson is a co-sponsor, click here. To review if your Senator is a co-sponsor, click here.
 

To the Editor:

A 68-year-old white man presented with a firm, gradually enlarging, mildly tender, grayish black papule with central ulceration on the left dorsal wrist of 4 months’ duration (Figure 1). His relevant medical history included multiple basal cell carcinomas (BCCs) and squamous cell carcinomas, as well as a single-lung transplant 2 years prior, for which he was on chronic immunosuppressive therapy with azathioprine, everolimus, tacrolimus, and prednisone. The clinical differential diagnosis included pigmented BCC, malignant melanoma, and ulcerated squamous cell carcinoma.

Histologic examination of the lesion (Figure 2) demonstrated irregular nodules of basaloid tumor cells with rounded nuclei, visible nucleoli, and scant cytoplasm involving the dermis. The tumor produced abrupt matrical-type keratinization, forming ghost cells. The lesion also contained frequent mitotic figures, apoptotic cells, focal areas of necrosis, and abundant melanin pigment. Admixed throughout the lesion were pigmented and dendritic melanocytic cells. The overlying epidermis was focally ulcerated with an adjacent localized connection between the tumor and the epidermis. Keratinocyte atypia was found in the surrounding epidermis, which contained melanophages, solar elastosis, and scattered chronic inflammatory cells. An immunohistochemical study (Figure 3) for tyrosinase demonstrated abundant admixed melanocytic cells. β-Catenin expression was shown in both nuclear and cytoplasmic distributions, and there was focal labeling on BerEP4 staining. Based on these findings, a diagnosis of melanocytic matrical carcinoma (MMC) was made.

Melanocytic matricoma (MM), a rare adnexal tumor, was first described in 1999 by Carlson et al.¹ A PubMed search of articles indexed for MEDLINE using the terms melanocytic and matricoma yielded 24 reported cases in the English-language literature.^1-17 It consists of an admixed population of basaloid matrical and supramatrical cells, ghost cells, and dendritic melanocytes in a well-circumscribed dermal nodule, typically without epidermal or adnexal connection. In comparison to the more commonly described pilomatricoma, which can be uncommonly pigmented, MM typically has only focal areas of ghost cells and lacks cystic architecture.^1,9,10,18 A granulomatous reaction to keratinaceous debris is variably present.^1,9,10 Histologically, the scattered dendritic melanocytes are classically benign, but cases demonstrating melanocyte atypia have been reported.^10,13 Melanocytic matricoma appears most commonly as a black or gray papule on sun-damaged skin in older men and tends not to recur following complete excision; thus, MM is considered to be a clinically benign neoplasm. Given the demographics and distribution of the lesions, exposure to UV radiation is thought to play a contributory role in the pathogenesis.^2,10,19 Melanocytic matricoma is believed to recapitulate the hair follicle in the anagen phase, where there is close interplay between matrical keratinocytes and melanocytes prior to cessation of melanogenesis during the catagen phase.^5,6,8,20,21 Evidence demonstrating highly conserved β-catenin and downstream lymphoid enhancer binding factor 1 (LEF1) expression, as well as pleckstrin homology-like domain, family A, member 1 (PHLDA1) expression (as a marker for follicular stem cells), points to constitutive activity in the Wnt signaling pathway in follicular stem cells of the bulge area as a major agent of tumorigenesis.¹²

Melanocytic matrical carcinoma, also known as malignant MM or matrical carcinoma with melanocytic hyperplasia, may be considered the malignant counterpart to MM.²² A PubMed search of articles indexed for MEDLINE using the terms melanocytic matrical carcinoma, malignant melanocytic matricoma, and matrical carcinoma with melanocytic hyperplasia, with review of references to identify additional citations, yielded 13 reported cases of MMC in the English-language literature (Table).^19,22-30 As with MM, MMC is a biphasic tumor with basaloid matrical and supramatrical cells; focal areas of ghost cells; and admixed, banal-appearing dendritic melanocytes. However, the basaloid component also demonstrates nuclear atypia, mitoses, occasional ulceration, and variably poor circumscription. Clinically these lesions can mimic pigmented BCC, malignant melanoma, or other malignant adnexal tumors.²⁵ Their natural history is unknown due to few reported cases, but they can be correlated with matrical carcinomas, which were first described by Weedon et al³¹ in 1980. A summary of more than 130 cases of matrical carcinomas in the English-language literature found that MMCs have high rates of local recurrence and metastasize in approximately 13% of cases. Wide local excision demonstrated lower rates of recurrence than simple excision (23% vs 83%), but there were insufficient cases to determine the incidence following Mohs micrographic surgery.³² Melanocytic matrical carcinomas also demonstrate mutations in the β-catenin pathway,pointing to a similar pathogenesis as their benign counterparts or perhaps direct malignant transformation.^25,33,34

A subset of MMCs are combined cutaneous tumors (CCTs) consisting of epithelial neoplasms in close association with malignant melanocytes. Two of the more common variants include dermal squamomelanocytic tumors, a term first used by Pool et al,³⁵ and malignant basomelanocytic tumors, as named by Erickson et al,³⁶ but trichoblastomelanomas and other types have been documented.³⁷ Although CCTs typically occur in the same patient populations as MMCs, namely elderly white men with chronically sun-damaged skin,they exhibit several important distinctions.^37-39 By definition, CCTs have a malignant melanocytic component, whereas melanocytes are nonneoplastic in MMCs. The pathogenesis may differ as well. Various mechanisms for the close association of epithelial tumors and melanoma have been proposed, including field cancerization, tumor collision, tumor-tumor metastases, tumor colonization, and others, though CCTs likely arise through combinations of these processes depending upon their subtype.^37-39 Paracrine signaling may play an important role in the pathogenesis of both tumors.^5,6,8,38 As with MMCs, the prognosis of CCTs is limited by relatively few reported cases. Despite advanced Breslow depths in many cases, these tumors display more indolent behavior suggestive of melanoma in situ rather than invasive melanoma, perhaps due to dependence upon epithelial paracrine factors.^37,39-42

Solid-organ transplant recipients have higher rates of more aggressive malignancies, of which skin cancer is the most common.^43-49 Squamous cell carcinoma of the skin accounts for 95% of cutaneous malignancies in this population and occurs at approximately 65 times the rate of the general population.⁵⁰ The risk of other skin cancers also is increased, though less dramatically, including BCC (10-fold increased risk) and melanoma (2- to 8-fold increased risk).^46,50-53 The cause likely is multifactorial, including older age, history of skin cancer pretransplant, more than 5 years posttransplant, male sex, and incrementally as Fitzpatrick skin type decreases from VI to I.^54-56 Immunosuppressive therapy also plays a role in tumorigenesis. Azathioprine metabolites have specifically been implicated in UVA radiation–induced promutagenic oxidative damage to DNA.⁵⁷ Other studies have found no significant differences in the type of immunosuppressant used but instead have correlated rates of skin cancer to overall immunosuppression.^48,55,58 Lung transplant recipients in particular demonstrate high rates of cutaneous malignancy, likely due in part to the necessity of more potent immunosuppressive regimens. Nearly one-third of patients develop a cutaneous malignancy by 5 years and nearly half by 10 years posttransplant.⁵⁵

We report a rare case of MMC in a solid-organ transplant recipient. We hypothesize that the combination of UV radiation exposure–induced photodamage acquired pretransplant in addition to an aggressive immunosuppressive regimen with azathioprine and other agents posttransplant contributed to the development of this patient’s rare malignancy. Although rare, these tumors should remain in the differential diagnosis of clinicians and pathologists caring for this unique patient population.

To the Editor:

A 68-year-old white man presented with a firm, gradually enlarging, mildly tender, grayish black papule with central ulceration on the left dorsal wrist of 4 months’ duration (Figure 1). His relevant medical history included multiple basal cell carcinomas (BCCs) and squamous cell carcinomas, as well as a single-lung transplant 2 years prior, for which he was on chronic immunosuppressive therapy with azathioprine, everolimus, tacrolimus, and prednisone. The clinical differential diagnosis included pigmented BCC, malignant melanoma, and ulcerated squamous cell carcinoma.

Histologic examination of the lesion (Figure 2) demonstrated irregular nodules of basaloid tumor cells with rounded nuclei, visible nucleoli, and scant cytoplasm involving the dermis. The tumor produced abrupt matrical-type keratinization, forming ghost cells. The lesion also contained frequent mitotic figures, apoptotic cells, focal areas of necrosis, and abundant melanin pigment. Admixed throughout the lesion were pigmented and dendritic melanocytic cells. The overlying epidermis was focally ulcerated with an adjacent localized connection between the tumor and the epidermis. Keratinocyte atypia was found in the surrounding epidermis, which contained melanophages, solar elastosis, and scattered chronic inflammatory cells. An immunohistochemical study (Figure 3) for tyrosinase demonstrated abundant admixed melanocytic cells. β-Catenin expression was shown in both nuclear and cytoplasmic distributions, and there was focal labeling on BerEP4 staining. Based on these findings, a diagnosis of melanocytic matrical carcinoma (MMC) was made.

Melanocytic matricoma (MM), a rare adnexal tumor, was first described in 1999 by Carlson et al.¹ A PubMed search of articles indexed for MEDLINE using the terms melanocytic and matricoma yielded 24 reported cases in the English-language literature.^1-17 It consists of an admixed population of basaloid matrical and supramatrical cells, ghost cells, and dendritic melanocytes in a well-circumscribed dermal nodule, typically without epidermal or adnexal connection. In comparison to the more commonly described pilomatricoma, which can be uncommonly pigmented, MM typically has only focal areas of ghost cells and lacks cystic architecture.^1,9,10,18 A granulomatous reaction to keratinaceous debris is variably present.^1,9,10 Histologically, the scattered dendritic melanocytes are classically benign, but cases demonstrating melanocyte atypia have been reported.^10,13 Melanocytic matricoma appears most commonly as a black or gray papule on sun-damaged skin in older men and tends not to recur following complete excision; thus, MM is considered to be a clinically benign neoplasm. Given the demographics and distribution of the lesions, exposure to UV radiation is thought to play a contributory role in the pathogenesis.^2,10,19 Melanocytic matricoma is believed to recapitulate the hair follicle in the anagen phase, where there is close interplay between matrical keratinocytes and melanocytes prior to cessation of melanogenesis during the catagen phase.^5,6,8,20,21 Evidence demonstrating highly conserved β-catenin and downstream lymphoid enhancer binding factor 1 (LEF1) expression, as well as pleckstrin homology-like domain, family A, member 1 (PHLDA1) expression (as a marker for follicular stem cells), points to constitutive activity in the Wnt signaling pathway in follicular stem cells of the bulge area as a major agent of tumorigenesis.¹²

Melanocytic matrical carcinoma, also known as malignant MM or matrical carcinoma with melanocytic hyperplasia, may be considered the malignant counterpart to MM.²² A PubMed search of articles indexed for MEDLINE using the terms melanocytic matrical carcinoma, malignant melanocytic matricoma, and matrical carcinoma with melanocytic hyperplasia, with review of references to identify additional citations, yielded 13 reported cases of MMC in the English-language literature (Table).^19,22-30 As with MM, MMC is a biphasic tumor with basaloid matrical and supramatrical cells; focal areas of ghost cells; and admixed, banal-appearing dendritic melanocytes. However, the basaloid component also demonstrates nuclear atypia, mitoses, occasional ulceration, and variably poor circumscription. Clinically these lesions can mimic pigmented BCC, malignant melanoma, or other malignant adnexal tumors.²⁵ Their natural history is unknown due to few reported cases, but they can be correlated with matrical carcinomas, which were first described by Weedon et al³¹ in 1980. A summary of more than 130 cases of matrical carcinomas in the English-language literature found that MMCs have high rates of local recurrence and metastasize in approximately 13% of cases. Wide local excision demonstrated lower rates of recurrence than simple excision (23% vs 83%), but there were insufficient cases to determine the incidence following Mohs micrographic surgery.³² Melanocytic matrical carcinomas also demonstrate mutations in the β-catenin pathway,pointing to a similar pathogenesis as their benign counterparts or perhaps direct malignant transformation.^25,33,34

A subset of MMCs are combined cutaneous tumors (CCTs) consisting of epithelial neoplasms in close association with malignant melanocytes. Two of the more common variants include dermal squamomelanocytic tumors, a term first used by Pool et al,³⁵ and malignant basomelanocytic tumors, as named by Erickson et al,³⁶ but trichoblastomelanomas and other types have been documented.³⁷ Although CCTs typically occur in the same patient populations as MMCs, namely elderly white men with chronically sun-damaged skin,they exhibit several important distinctions.^37-39 By definition, CCTs have a malignant melanocytic component, whereas melanocytes are nonneoplastic in MMCs. The pathogenesis may differ as well. Various mechanisms for the close association of epithelial tumors and melanoma have been proposed, including field cancerization, tumor collision, tumor-tumor metastases, tumor colonization, and others, though CCTs likely arise through combinations of these processes depending upon their subtype.^37-39 Paracrine signaling may play an important role in the pathogenesis of both tumors.^5,6,8,38 As with MMCs, the prognosis of CCTs is limited by relatively few reported cases. Despite advanced Breslow depths in many cases, these tumors display more indolent behavior suggestive of melanoma in situ rather than invasive melanoma, perhaps due to dependence upon epithelial paracrine factors.^37,39-42

Solid-organ transplant recipients have higher rates of more aggressive malignancies, of which skin cancer is the most common.^43-49 Squamous cell carcinoma of the skin accounts for 95% of cutaneous malignancies in this population and occurs at approximately 65 times the rate of the general population.⁵⁰ The risk of other skin cancers also is increased, though less dramatically, including BCC (10-fold increased risk) and melanoma (2- to 8-fold increased risk).^46,50-53 The cause likely is multifactorial, including older age, history of skin cancer pretransplant, more than 5 years posttransplant, male sex, and incrementally as Fitzpatrick skin type decreases from VI to I.^54-56 Immunosuppressive therapy also plays a role in tumorigenesis. Azathioprine metabolites have specifically been implicated in UVA radiation–induced promutagenic oxidative damage to DNA.⁵⁷ Other studies have found no significant differences in the type of immunosuppressant used but instead have correlated rates of skin cancer to overall immunosuppression.^48,55,58 Lung transplant recipients in particular demonstrate high rates of cutaneous malignancy, likely due in part to the necessity of more potent immunosuppressive regimens. Nearly one-third of patients develop a cutaneous malignancy by 5 years and nearly half by 10 years posttransplant.⁵⁵

We report a rare case of MMC in a solid-organ transplant recipient. We hypothesize that the combination of UV radiation exposure–induced photodamage acquired pretransplant in addition to an aggressive immunosuppressive regimen with azathioprine and other agents posttransplant contributed to the development of this patient’s rare malignancy. Although rare, these tumors should remain in the differential diagnosis of clinicians and pathologists caring for this unique patient population.

To the Editor:

A 68-year-old white man presented with a firm, gradually enlarging, mildly tender, grayish black papule with central ulceration on the left dorsal wrist of 4 months’ duration (Figure 1). His relevant medical history included multiple basal cell carcinomas (BCCs) and squamous cell carcinomas, as well as a single-lung transplant 2 years prior, for which he was on chronic immunosuppressive therapy with azathioprine, everolimus, tacrolimus, and prednisone. The clinical differential diagnosis included pigmented BCC, malignant melanoma, and ulcerated squamous cell carcinoma.

Histologic examination of the lesion (Figure 2) demonstrated irregular nodules of basaloid tumor cells with rounded nuclei, visible nucleoli, and scant cytoplasm involving the dermis. The tumor produced abrupt matrical-type keratinization, forming ghost cells. The lesion also contained frequent mitotic figures, apoptotic cells, focal areas of necrosis, and abundant melanin pigment. Admixed throughout the lesion were pigmented and dendritic melanocytic cells. The overlying epidermis was focally ulcerated with an adjacent localized connection between the tumor and the epidermis. Keratinocyte atypia was found in the surrounding epidermis, which contained melanophages, solar elastosis, and scattered chronic inflammatory cells. An immunohistochemical study (Figure 3) for tyrosinase demonstrated abundant admixed melanocytic cells. β-Catenin expression was shown in both nuclear and cytoplasmic distributions, and there was focal labeling on BerEP4 staining. Based on these findings, a diagnosis of melanocytic matrical carcinoma (MMC) was made.

Melanocytic matricoma (MM), a rare adnexal tumor, was first described in 1999 by Carlson et al.¹ A PubMed search of articles indexed for MEDLINE using the terms melanocytic and matricoma yielded 24 reported cases in the English-language literature.^1-17 It consists of an admixed population of basaloid matrical and supramatrical cells, ghost cells, and dendritic melanocytes in a well-circumscribed dermal nodule, typically without epidermal or adnexal connection. In comparison to the more commonly described pilomatricoma, which can be uncommonly pigmented, MM typically has only focal areas of ghost cells and lacks cystic architecture.^1,9,10,18 A granulomatous reaction to keratinaceous debris is variably present.^1,9,10 Histologically, the scattered dendritic melanocytes are classically benign, but cases demonstrating melanocyte atypia have been reported.^10,13 Melanocytic matricoma appears most commonly as a black or gray papule on sun-damaged skin in older men and tends not to recur following complete excision; thus, MM is considered to be a clinically benign neoplasm. Given the demographics and distribution of the lesions, exposure to UV radiation is thought to play a contributory role in the pathogenesis.^2,10,19 Melanocytic matricoma is believed to recapitulate the hair follicle in the anagen phase, where there is close interplay between matrical keratinocytes and melanocytes prior to cessation of melanogenesis during the catagen phase.^5,6,8,20,21 Evidence demonstrating highly conserved β-catenin and downstream lymphoid enhancer binding factor 1 (LEF1) expression, as well as pleckstrin homology-like domain, family A, member 1 (PHLDA1) expression (as a marker for follicular stem cells), points to constitutive activity in the Wnt signaling pathway in follicular stem cells of the bulge area as a major agent of tumorigenesis.¹²

Melanocytic matrical carcinoma, also known as malignant MM or matrical carcinoma with melanocytic hyperplasia, may be considered the malignant counterpart to MM.²² A PubMed search of articles indexed for MEDLINE using the terms melanocytic matrical carcinoma, malignant melanocytic matricoma, and matrical carcinoma with melanocytic hyperplasia, with review of references to identify additional citations, yielded 13 reported cases of MMC in the English-language literature (Table).^19,22-30 As with MM, MMC is a biphasic tumor with basaloid matrical and supramatrical cells; focal areas of ghost cells; and admixed, banal-appearing dendritic melanocytes. However, the basaloid component also demonstrates nuclear atypia, mitoses, occasional ulceration, and variably poor circumscription. Clinically these lesions can mimic pigmented BCC, malignant melanoma, or other malignant adnexal tumors.²⁵ Their natural history is unknown due to few reported cases, but they can be correlated with matrical carcinomas, which were first described by Weedon et al³¹ in 1980. A summary of more than 130 cases of matrical carcinomas in the English-language literature found that MMCs have high rates of local recurrence and metastasize in approximately 13% of cases. Wide local excision demonstrated lower rates of recurrence than simple excision (23% vs 83%), but there were insufficient cases to determine the incidence following Mohs micrographic surgery.³² Melanocytic matrical carcinomas also demonstrate mutations in the β-catenin pathway,pointing to a similar pathogenesis as their benign counterparts or perhaps direct malignant transformation.^25,33,34

A subset of MMCs are combined cutaneous tumors (CCTs) consisting of epithelial neoplasms in close association with malignant melanocytes. Two of the more common variants include dermal squamomelanocytic tumors, a term first used by Pool et al,³⁵ and malignant basomelanocytic tumors, as named by Erickson et al,³⁶ but trichoblastomelanomas and other types have been documented.³⁷ Although CCTs typically occur in the same patient populations as MMCs, namely elderly white men with chronically sun-damaged skin,they exhibit several important distinctions.^37-39 By definition, CCTs have a malignant melanocytic component, whereas melanocytes are nonneoplastic in MMCs. The pathogenesis may differ as well. Various mechanisms for the close association of epithelial tumors and melanoma have been proposed, including field cancerization, tumor collision, tumor-tumor metastases, tumor colonization, and others, though CCTs likely arise through combinations of these processes depending upon their subtype.^37-39 Paracrine signaling may play an important role in the pathogenesis of both tumors.^5,6,8,38 As with MMCs, the prognosis of CCTs is limited by relatively few reported cases. Despite advanced Breslow depths in many cases, these tumors display more indolent behavior suggestive of melanoma in situ rather than invasive melanoma, perhaps due to dependence upon epithelial paracrine factors.^37,39-42

Solid-organ transplant recipients have higher rates of more aggressive malignancies, of which skin cancer is the most common.^43-49 Squamous cell carcinoma of the skin accounts for 95% of cutaneous malignancies in this population and occurs at approximately 65 times the rate of the general population.⁵⁰ The risk of other skin cancers also is increased, though less dramatically, including BCC (10-fold increased risk) and melanoma (2- to 8-fold increased risk).^46,50-53 The cause likely is multifactorial, including older age, history of skin cancer pretransplant, more than 5 years posttransplant, male sex, and incrementally as Fitzpatrick skin type decreases from VI to I.^54-56 Immunosuppressive therapy also plays a role in tumorigenesis. Azathioprine metabolites have specifically been implicated in UVA radiation–induced promutagenic oxidative damage to DNA.⁵⁷ Other studies have found no significant differences in the type of immunosuppressant used but instead have correlated rates of skin cancer to overall immunosuppression.^48,55,58 Lung transplant recipients in particular demonstrate high rates of cutaneous malignancy, likely due in part to the necessity of more potent immunosuppressive regimens. Nearly one-third of patients develop a cutaneous malignancy by 5 years and nearly half by 10 years posttransplant.⁵⁵

We report a rare case of MMC in a solid-organ transplant recipient. We hypothesize that the combination of UV radiation exposure–induced photodamage acquired pretransplant in addition to an aggressive immunosuppressive regimen with azathioprine and other agents posttransplant contributed to the development of this patient’s rare malignancy. Although rare, these tumors should remain in the differential diagnosis of clinicians and pathologists caring for this unique patient population.

Vandetanib is a once-daily oral multikinase inhibitor that targets the rearranged during transfection (RET) tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor. It has shown efficacy at doses of 300 mg daily in the treatment of progressive medullary thyroid cancer and has shown promise in non–small cell lung cancer and breast cancer. Vandetanib’s toxicity profile includes QT prolongation, diarrhea, and rash.^1-3 Cutaneous involvement has been described in the literature as a photodistributed drug reaction with both erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)–like eruptions, phototoxicity, and photoallergy (Table).^4-12 Photoinduction is the common thread, but various mechanisms have been proposed, including drug deposition within the dermis and direct toxicity to keratinocytes; however, an understanding of the varied presentation is lacking.

We present 3 cases of vandetanib photoinduced cutaneous toxicities and review the literature on this novel kinase inhibitor. This discussion highlights the spectrum of photosensitivity reactions to vandetanib among patients with varying histologic and clinical presentations.

Case Reports

Patient 1A
74-year-old woman with a history of recurrent metastatic squamous cell carcinoma of the cervix and Fitzpatrick skin type III presented with erythematous, well-demarcated, photodistributed, eczematous papules that were coalescing into plaques on the scalp, hands, and face. The rash appeared sharply demarcated at the wrists bilaterally and principally involved the dorsal sun-exposed areas of her hands (Figure 1). The rash also involved the face and the V of the neck with sharp demarcation. Two weeks prior to onset, she initiated a phase 1 trial of oral vandetanib 100 mg twice daily and oral everolimus 5 mg daily. She did not recall practicing sun protection or experiencing increased sun exposure after starting that trial. The patient demonstrated symptom improvement with desonide cream, hydrocortisone cream 2.5%, and over-the-counter analgesic cream while continuing with the study drugs. However, she developed new, warm, painful papules on the hands and face. Phototesting and biopsy were not performed, and the etiology of the photosensitivity was unknown.

The patient was counseled about regular sun protection and was prescribed triamcinolone cream 0.1% for the arms and hydrocortisone cream 2.5% for the affected facial areas. Therapy with vandetanib and everolimus was continued without dose reduction or further cutaneous eruptions.

Patient 2
A 54-year-old man with a history of progressive medullary thyroid carcinoma and Fitzpatrick skin type II presented with erythematous, well-demarcated, photodistributed, edematous plaques and bullae of the head and neck, bilateral dorsal hands, and bilateral palms of 2 weeks’ duration. The rash spared the upper back and chest with a well-demarcated border (Figure 2A). There were ulcerations and erosions at the base of the neck and the dorsal hands (Figure 2B). He also had conjunctivitis but uninvolved oral and genital mucosae.

Two weeks before the rash appeared, oral vandetanib 300 mg daily was initiated. The patient initially noted some dry skin, which progressed to an eruption involving the face and neck and later the hands with palmar blistering and desquamation. Medication cessation for 1 month led to moderate improvement of the rash on the face and neck. He had not been practicing sun protection but did wear a baseball cap when outside. The patient did not recall an incidence of increased sun exposure. He underwent a skin biopsy of the right dorsal hand, which revealed interface dermatitis with dyskeratosis and subepidermal and intraepidermal bullae (Figure 3). The biopsy findings were most consistent with a phototoxic eruption. Phototesting was not performed.

Patient 3
A 73-year-old man with a history of metastatic lung carcinoma and Fitzpatrick skin type II presented with a rash on the scalp, face, and arms of 2.5 weeks’ duration. There was sharp demarcation at the edges of sun-exposed skin, and no bullae were noted (Figure 4). Prior to presentation, the patient started a 4-week phase 1 trial with vandetanib 300 mg daily and everolimus 10 mg daily. He did not recall any episodes of increased sun exposure. A punch biopsy of the arm showed an interface dermatitis suggestive of a phototoxic reaction. Phototesting was not performed to further clarify if there was a diminished minimal erythema dose with UVA or UVB radiation. Both drugs were discontinued, strict photoprotection was practiced, and triamcinolone cream 0.1% was initiated with resolution of rash. Vandetanib and everolimus were resumed at initial doses with strict photoprotection, and the rash has not recurred.

Comment

Adverse Events Associated With Vandetanib
Vandetanib is a novel multikinase inhibitor that targets RET tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor.^1,2 It currently is approved by the US Food and Drug Administration for the treatment of progressive medullary thyroid cancer and is being used in clinical trials for non–small cell lung cancer, glioma, advanced biliary tract cancer, breast cancer, and other advanced solid malignancies. Frequently reported adverse events (AEs) include QT prolongation, diarrhea, and rash.^1-3 In a large phase 3 trial, 45% of patients had a rash; of these, 4% were grade 3 and above.³ The most common reasons for dose decrease or cessation were diarrhea and rash (1% and 1.3%, respectively).¹³ Outside of a trial setting, 75% (45/60) of patients in one French study reported a cutaneous AE, with photosensitivity noted in 22% (13/60). Thus, cutaneous reactions tend to be a common occurrence for patients on this drug, requiring diligent dermatologic examinations.¹⁴ In one meta-analysis comprising 9 studies with a total of 2961 patients, the incidence of all-grade rash was 46.1% (95% CI, 40.6%-51.8%), and it was concluded that vandetanib has the highest association of all-grade rash among the anti–vascular endothelial growth factor tyrosine kinase inhibitors. In this meta-analysis, the specific diagnosis of AEs was not further classified.¹⁵ In another cohort of vandetanib-treated patients, as many as 37% (28/63) of patients had photosensitivity, with no clarification of the etiology.¹⁶

Photoallergic vs Phototoxic Reactions
Photosensitivity reactions are cutaneous reactions that occur from UV light exposure, typically in conjunction with a photosensitizing agent. Photosensitivity reactions can be further classified into phototoxic and photoallergic reactions, which can be distinguished by histopathologic evaluation and history. Although phototoxic reactions will cause keratinocyte necrosis similar to a sunburn, photoallergic reactions will cause epidermal spongiosis similar to allergic contact dermatitis or eczema. Also, phototoxic reactions appear within 1 to 2 days of UV exposure and often are painful, whereas photoallergic reactions can be delayed for 2 to 3 weeks and usually are pruritic. Photosensitivity reactions related to vandetanib have been reported and are summarized in the Table.^4-12

Although reported cutaneous reactions to vandetanib thus far in the literature were reported as photoinduced reactions, there have been isolated case reports of other eruptions including cutaneous pigmentation⁵ and one case of SJS.⁹ According to a PubMed search of articles indexed for MEDLINE using the terms vandetanib and rash, we found that there are a variety of clinical findings, but most of the reported photosensitivity cases were phototoxic. Fava et al⁷ and Goldstein et al¹² both reported 1 photoallergic reaction each, plus patient 1 in our case series was noted to have a photoallergic reaction. Phototoxic reactions were reported in 4 patients (including our patient 2) who had dyskeratotic keratinocytes and vacuolar degeneration of the basal layer on histopathology.^4,8 Fava et al⁷ described a lichenoid infiltrate with spongiosis consistent with a photoallergic reaction, but Chang et al⁴ and Bota et al¹¹ described a lichenoid infiltrate with dyskeratotic cells. Also, Giacchero et al¹⁶ described a photosensitivity reaction in 28 of 63 patients. Although only 6 patients had biopsies performed, the range of photosensitivity reactions was demonstrated with lichenoid, dyskeratotic, and spongiotic reactions. However, the cases were not further defined as photoallergic or phototoxic.¹⁶ Vandetanib also has been associated with cutaneous blue pigmentation after likely phototoxic reactions. Pigment changes occurred after photosensitivity, but the clinical presentation of photosensitivity was not further characterized.^5,16

Classic Drug Eruptions
Two patients were described as having classic drug eruptions—EM¹⁰ and SJS⁹—in photodistributed locations. Histologically, these entities are identical to phototoxic reactions, resulting in epidermal necrosis and an interface dermatitis, but the presence of targetoid lesions on the palms prompted the diagnosis of photodistributed EM and SJS in both cases.^9,10 Unique to the SJS case was oral involvement.⁹

Distinguishing between a phototoxic reaction and photodistributed EM or SJS may be inconsequential if both can be prevented with photoprotection. Rechallenging patients with vandetanib while practicing photoprotection would help to clarify the mechanism, though this course is not always practical.

Mechanism of Action
As seen in our case series, cutaneous reactions occurred only on sun-exposed surfaces, and patients presented with sharp cutoff points that spared non–sun-exposed areas. Although clinically organized as a subtype of photosensitivity, the phototoxicity mechanism of action is considered a direct toxic effect on keratinocytes, which explains the histopathologic finding of dyskeratotic cells and the clinical spectrum of sunburn reaction, phototoxic EM, and SJS. UVA1 induces 2 photoproducts of vandetanib via a UVA1-mediated debromination process,¹⁷ but these photoproducts are not responsible for epidermal dyskeratosis.¹⁸ It was subsequently demonstrated that keratinocyte death was induced by apoptosis through photoinduced DNA cleavage and the formation of an aryl radical, which can induce further DNA damage.¹⁸ Caro-Gutierrez et al¹⁰ demonstrated a lowered minimal erythema dose in their patient with vandetanib-induced phototoxic EM.

Conversely, photoallergic reactions are considered immune-mediated delayed-type hypersensitivity reactions.^4,7,11 Although the mechanism of a photoallergic reaction remains unclear, it is possible that vandetanib or a metabolite (in susceptible patients) induces an immune-mediated delayed-type hypersensitivity reaction with repeated exposure to the compound, which may explain the varied timing of photoallergic onset, including the events featured in the Bota et al¹¹ case that occurred several months after drug initiation.

Conclusion

Considering the high prevalence of cutaneous AEs, especially varied photosensitivity reactions, these cases emphasize the importance of sun protection to help prevent dose reduction or drug cessation among patients taking vandetanib therapy.

Vandetanib is a once-daily oral multikinase inhibitor that targets the rearranged during transfection (RET) tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor. It has shown efficacy at doses of 300 mg daily in the treatment of progressive medullary thyroid cancer and has shown promise in non–small cell lung cancer and breast cancer. Vandetanib’s toxicity profile includes QT prolongation, diarrhea, and rash.^1-3 Cutaneous involvement has been described in the literature as a photodistributed drug reaction with both erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)–like eruptions, phototoxicity, and photoallergy (Table).^4-12 Photoinduction is the common thread, but various mechanisms have been proposed, including drug deposition within the dermis and direct toxicity to keratinocytes; however, an understanding of the varied presentation is lacking.

We present 3 cases of vandetanib photoinduced cutaneous toxicities and review the literature on this novel kinase inhibitor. This discussion highlights the spectrum of photosensitivity reactions to vandetanib among patients with varying histologic and clinical presentations.

Case Reports

Patient 1A
74-year-old woman with a history of recurrent metastatic squamous cell carcinoma of the cervix and Fitzpatrick skin type III presented with erythematous, well-demarcated, photodistributed, eczematous papules that were coalescing into plaques on the scalp, hands, and face. The rash appeared sharply demarcated at the wrists bilaterally and principally involved the dorsal sun-exposed areas of her hands (Figure 1). The rash also involved the face and the V of the neck with sharp demarcation. Two weeks prior to onset, she initiated a phase 1 trial of oral vandetanib 100 mg twice daily and oral everolimus 5 mg daily. She did not recall practicing sun protection or experiencing increased sun exposure after starting that trial. The patient demonstrated symptom improvement with desonide cream, hydrocortisone cream 2.5%, and over-the-counter analgesic cream while continuing with the study drugs. However, she developed new, warm, painful papules on the hands and face. Phototesting and biopsy were not performed, and the etiology of the photosensitivity was unknown.

The patient was counseled about regular sun protection and was prescribed triamcinolone cream 0.1% for the arms and hydrocortisone cream 2.5% for the affected facial areas. Therapy with vandetanib and everolimus was continued without dose reduction or further cutaneous eruptions.

Patient 2
A 54-year-old man with a history of progressive medullary thyroid carcinoma and Fitzpatrick skin type II presented with erythematous, well-demarcated, photodistributed, edematous plaques and bullae of the head and neck, bilateral dorsal hands, and bilateral palms of 2 weeks’ duration. The rash spared the upper back and chest with a well-demarcated border (Figure 2A). There were ulcerations and erosions at the base of the neck and the dorsal hands (Figure 2B). He also had conjunctivitis but uninvolved oral and genital mucosae.

Two weeks before the rash appeared, oral vandetanib 300 mg daily was initiated. The patient initially noted some dry skin, which progressed to an eruption involving the face and neck and later the hands with palmar blistering and desquamation. Medication cessation for 1 month led to moderate improvement of the rash on the face and neck. He had not been practicing sun protection but did wear a baseball cap when outside. The patient did not recall an incidence of increased sun exposure. He underwent a skin biopsy of the right dorsal hand, which revealed interface dermatitis with dyskeratosis and subepidermal and intraepidermal bullae (Figure 3). The biopsy findings were most consistent with a phototoxic eruption. Phototesting was not performed.

Patient 3
A 73-year-old man with a history of metastatic lung carcinoma and Fitzpatrick skin type II presented with a rash on the scalp, face, and arms of 2.5 weeks’ duration. There was sharp demarcation at the edges of sun-exposed skin, and no bullae were noted (Figure 4). Prior to presentation, the patient started a 4-week phase 1 trial with vandetanib 300 mg daily and everolimus 10 mg daily. He did not recall any episodes of increased sun exposure. A punch biopsy of the arm showed an interface dermatitis suggestive of a phototoxic reaction. Phototesting was not performed to further clarify if there was a diminished minimal erythema dose with UVA or UVB radiation. Both drugs were discontinued, strict photoprotection was practiced, and triamcinolone cream 0.1% was initiated with resolution of rash. Vandetanib and everolimus were resumed at initial doses with strict photoprotection, and the rash has not recurred.

Comment

Adverse Events Associated With Vandetanib
Vandetanib is a novel multikinase inhibitor that targets RET tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor.^1,2 It currently is approved by the US Food and Drug Administration for the treatment of progressive medullary thyroid cancer and is being used in clinical trials for non–small cell lung cancer, glioma, advanced biliary tract cancer, breast cancer, and other advanced solid malignancies. Frequently reported adverse events (AEs) include QT prolongation, diarrhea, and rash.^1-3 In a large phase 3 trial, 45% of patients had a rash; of these, 4% were grade 3 and above.³ The most common reasons for dose decrease or cessation were diarrhea and rash (1% and 1.3%, respectively).¹³ Outside of a trial setting, 75% (45/60) of patients in one French study reported a cutaneous AE, with photosensitivity noted in 22% (13/60). Thus, cutaneous reactions tend to be a common occurrence for patients on this drug, requiring diligent dermatologic examinations.¹⁴ In one meta-analysis comprising 9 studies with a total of 2961 patients, the incidence of all-grade rash was 46.1% (95% CI, 40.6%-51.8%), and it was concluded that vandetanib has the highest association of all-grade rash among the anti–vascular endothelial growth factor tyrosine kinase inhibitors. In this meta-analysis, the specific diagnosis of AEs was not further classified.¹⁵ In another cohort of vandetanib-treated patients, as many as 37% (28/63) of patients had photosensitivity, with no clarification of the etiology.¹⁶

Photoallergic vs Phototoxic Reactions
Photosensitivity reactions are cutaneous reactions that occur from UV light exposure, typically in conjunction with a photosensitizing agent. Photosensitivity reactions can be further classified into phototoxic and photoallergic reactions, which can be distinguished by histopathologic evaluation and history. Although phototoxic reactions will cause keratinocyte necrosis similar to a sunburn, photoallergic reactions will cause epidermal spongiosis similar to allergic contact dermatitis or eczema. Also, phototoxic reactions appear within 1 to 2 days of UV exposure and often are painful, whereas photoallergic reactions can be delayed for 2 to 3 weeks and usually are pruritic. Photosensitivity reactions related to vandetanib have been reported and are summarized in the Table.^4-12

Although reported cutaneous reactions to vandetanib thus far in the literature were reported as photoinduced reactions, there have been isolated case reports of other eruptions including cutaneous pigmentation⁵ and one case of SJS.⁹ According to a PubMed search of articles indexed for MEDLINE using the terms vandetanib and rash, we found that there are a variety of clinical findings, but most of the reported photosensitivity cases were phototoxic. Fava et al⁷ and Goldstein et al¹² both reported 1 photoallergic reaction each, plus patient 1 in our case series was noted to have a photoallergic reaction. Phototoxic reactions were reported in 4 patients (including our patient 2) who had dyskeratotic keratinocytes and vacuolar degeneration of the basal layer on histopathology.^4,8 Fava et al⁷ described a lichenoid infiltrate with spongiosis consistent with a photoallergic reaction, but Chang et al⁴ and Bota et al¹¹ described a lichenoid infiltrate with dyskeratotic cells. Also, Giacchero et al¹⁶ described a photosensitivity reaction in 28 of 63 patients. Although only 6 patients had biopsies performed, the range of photosensitivity reactions was demonstrated with lichenoid, dyskeratotic, and spongiotic reactions. However, the cases were not further defined as photoallergic or phototoxic.¹⁶ Vandetanib also has been associated with cutaneous blue pigmentation after likely phototoxic reactions. Pigment changes occurred after photosensitivity, but the clinical presentation of photosensitivity was not further characterized.^5,16

Classic Drug Eruptions
Two patients were described as having classic drug eruptions—EM¹⁰ and SJS⁹—in photodistributed locations. Histologically, these entities are identical to phototoxic reactions, resulting in epidermal necrosis and an interface dermatitis, but the presence of targetoid lesions on the palms prompted the diagnosis of photodistributed EM and SJS in both cases.^9,10 Unique to the SJS case was oral involvement.⁹

Distinguishing between a phototoxic reaction and photodistributed EM or SJS may be inconsequential if both can be prevented with photoprotection. Rechallenging patients with vandetanib while practicing photoprotection would help to clarify the mechanism, though this course is not always practical.

Mechanism of Action
As seen in our case series, cutaneous reactions occurred only on sun-exposed surfaces, and patients presented with sharp cutoff points that spared non–sun-exposed areas. Although clinically organized as a subtype of photosensitivity, the phototoxicity mechanism of action is considered a direct toxic effect on keratinocytes, which explains the histopathologic finding of dyskeratotic cells and the clinical spectrum of sunburn reaction, phototoxic EM, and SJS. UVA1 induces 2 photoproducts of vandetanib via a UVA1-mediated debromination process,¹⁷ but these photoproducts are not responsible for epidermal dyskeratosis.¹⁸ It was subsequently demonstrated that keratinocyte death was induced by apoptosis through photoinduced DNA cleavage and the formation of an aryl radical, which can induce further DNA damage.¹⁸ Caro-Gutierrez et al¹⁰ demonstrated a lowered minimal erythema dose in their patient with vandetanib-induced phototoxic EM.

Conversely, photoallergic reactions are considered immune-mediated delayed-type hypersensitivity reactions.^4,7,11 Although the mechanism of a photoallergic reaction remains unclear, it is possible that vandetanib or a metabolite (in susceptible patients) induces an immune-mediated delayed-type hypersensitivity reaction with repeated exposure to the compound, which may explain the varied timing of photoallergic onset, including the events featured in the Bota et al¹¹ case that occurred several months after drug initiation.

Conclusion

Considering the high prevalence of cutaneous AEs, especially varied photosensitivity reactions, these cases emphasize the importance of sun protection to help prevent dose reduction or drug cessation among patients taking vandetanib therapy.

Vandetanib is a once-daily oral multikinase inhibitor that targets the rearranged during transfection (RET) tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor. It has shown efficacy at doses of 300 mg daily in the treatment of progressive medullary thyroid cancer and has shown promise in non–small cell lung cancer and breast cancer. Vandetanib’s toxicity profile includes QT prolongation, diarrhea, and rash.^1-3 Cutaneous involvement has been described in the literature as a photodistributed drug reaction with both erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)–like eruptions, phototoxicity, and photoallergy (Table).^4-12 Photoinduction is the common thread, but various mechanisms have been proposed, including drug deposition within the dermis and direct toxicity to keratinocytes; however, an understanding of the varied presentation is lacking.

We present 3 cases of vandetanib photoinduced cutaneous toxicities and review the literature on this novel kinase inhibitor. This discussion highlights the spectrum of photosensitivity reactions to vandetanib among patients with varying histologic and clinical presentations.

Case Reports

Patient 1A
74-year-old woman with a history of recurrent metastatic squamous cell carcinoma of the cervix and Fitzpatrick skin type III presented with erythematous, well-demarcated, photodistributed, eczematous papules that were coalescing into plaques on the scalp, hands, and face. The rash appeared sharply demarcated at the wrists bilaterally and principally involved the dorsal sun-exposed areas of her hands (Figure 1). The rash also involved the face and the V of the neck with sharp demarcation. Two weeks prior to onset, she initiated a phase 1 trial of oral vandetanib 100 mg twice daily and oral everolimus 5 mg daily. She did not recall practicing sun protection or experiencing increased sun exposure after starting that trial. The patient demonstrated symptom improvement with desonide cream, hydrocortisone cream 2.5%, and over-the-counter analgesic cream while continuing with the study drugs. However, she developed new, warm, painful papules on the hands and face. Phototesting and biopsy were not performed, and the etiology of the photosensitivity was unknown.

The patient was counseled about regular sun protection and was prescribed triamcinolone cream 0.1% for the arms and hydrocortisone cream 2.5% for the affected facial areas. Therapy with vandetanib and everolimus was continued without dose reduction or further cutaneous eruptions.

Patient 2
A 54-year-old man with a history of progressive medullary thyroid carcinoma and Fitzpatrick skin type II presented with erythematous, well-demarcated, photodistributed, edematous plaques and bullae of the head and neck, bilateral dorsal hands, and bilateral palms of 2 weeks’ duration. The rash spared the upper back and chest with a well-demarcated border (Figure 2A). There were ulcerations and erosions at the base of the neck and the dorsal hands (Figure 2B). He also had conjunctivitis but uninvolved oral and genital mucosae.

Two weeks before the rash appeared, oral vandetanib 300 mg daily was initiated. The patient initially noted some dry skin, which progressed to an eruption involving the face and neck and later the hands with palmar blistering and desquamation. Medication cessation for 1 month led to moderate improvement of the rash on the face and neck. He had not been practicing sun protection but did wear a baseball cap when outside. The patient did not recall an incidence of increased sun exposure. He underwent a skin biopsy of the right dorsal hand, which revealed interface dermatitis with dyskeratosis and subepidermal and intraepidermal bullae (Figure 3). The biopsy findings were most consistent with a phototoxic eruption. Phototesting was not performed.

Patient 3
A 73-year-old man with a history of metastatic lung carcinoma and Fitzpatrick skin type II presented with a rash on the scalp, face, and arms of 2.5 weeks’ duration. There was sharp demarcation at the edges of sun-exposed skin, and no bullae were noted (Figure 4). Prior to presentation, the patient started a 4-week phase 1 trial with vandetanib 300 mg daily and everolimus 10 mg daily. He did not recall any episodes of increased sun exposure. A punch biopsy of the arm showed an interface dermatitis suggestive of a phototoxic reaction. Phototesting was not performed to further clarify if there was a diminished minimal erythema dose with UVA or UVB radiation. Both drugs were discontinued, strict photoprotection was practiced, and triamcinolone cream 0.1% was initiated with resolution of rash. Vandetanib and everolimus were resumed at initial doses with strict photoprotection, and the rash has not recurred.

Comment

Adverse Events Associated With Vandetanib
Vandetanib is a novel multikinase inhibitor that targets RET tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor.^1,2 It currently is approved by the US Food and Drug Administration for the treatment of progressive medullary thyroid cancer and is being used in clinical trials for non–small cell lung cancer, glioma, advanced biliary tract cancer, breast cancer, and other advanced solid malignancies. Frequently reported adverse events (AEs) include QT prolongation, diarrhea, and rash.^1-3 In a large phase 3 trial, 45% of patients had a rash; of these, 4% were grade 3 and above.³ The most common reasons for dose decrease or cessation were diarrhea and rash (1% and 1.3%, respectively).¹³ Outside of a trial setting, 75% (45/60) of patients in one French study reported a cutaneous AE, with photosensitivity noted in 22% (13/60). Thus, cutaneous reactions tend to be a common occurrence for patients on this drug, requiring diligent dermatologic examinations.¹⁴ In one meta-analysis comprising 9 studies with a total of 2961 patients, the incidence of all-grade rash was 46.1% (95% CI, 40.6%-51.8%), and it was concluded that vandetanib has the highest association of all-grade rash among the anti–vascular endothelial growth factor tyrosine kinase inhibitors. In this meta-analysis, the specific diagnosis of AEs was not further classified.¹⁵ In another cohort of vandetanib-treated patients, as many as 37% (28/63) of patients had photosensitivity, with no clarification of the etiology.¹⁶

Photoallergic vs Phototoxic Reactions
Photosensitivity reactions are cutaneous reactions that occur from UV light exposure, typically in conjunction with a photosensitizing agent. Photosensitivity reactions can be further classified into phototoxic and photoallergic reactions, which can be distinguished by histopathologic evaluation and history. Although phototoxic reactions will cause keratinocyte necrosis similar to a sunburn, photoallergic reactions will cause epidermal spongiosis similar to allergic contact dermatitis or eczema. Also, phototoxic reactions appear within 1 to 2 days of UV exposure and often are painful, whereas photoallergic reactions can be delayed for 2 to 3 weeks and usually are pruritic. Photosensitivity reactions related to vandetanib have been reported and are summarized in the Table.^4-12

Although reported cutaneous reactions to vandetanib thus far in the literature were reported as photoinduced reactions, there have been isolated case reports of other eruptions including cutaneous pigmentation⁵ and one case of SJS.⁹ According to a PubMed search of articles indexed for MEDLINE using the terms vandetanib and rash, we found that there are a variety of clinical findings, but most of the reported photosensitivity cases were phototoxic. Fava et al⁷ and Goldstein et al¹² both reported 1 photoallergic reaction each, plus patient 1 in our case series was noted to have a photoallergic reaction. Phototoxic reactions were reported in 4 patients (including our patient 2) who had dyskeratotic keratinocytes and vacuolar degeneration of the basal layer on histopathology.^4,8 Fava et al⁷ described a lichenoid infiltrate with spongiosis consistent with a photoallergic reaction, but Chang et al⁴ and Bota et al¹¹ described a lichenoid infiltrate with dyskeratotic cells. Also, Giacchero et al¹⁶ described a photosensitivity reaction in 28 of 63 patients. Although only 6 patients had biopsies performed, the range of photosensitivity reactions was demonstrated with lichenoid, dyskeratotic, and spongiotic reactions. However, the cases were not further defined as photoallergic or phototoxic.¹⁶ Vandetanib also has been associated with cutaneous blue pigmentation after likely phototoxic reactions. Pigment changes occurred after photosensitivity, but the clinical presentation of photosensitivity was not further characterized.^5,16

Classic Drug Eruptions
Two patients were described as having classic drug eruptions—EM¹⁰ and SJS⁹—in photodistributed locations. Histologically, these entities are identical to phototoxic reactions, resulting in epidermal necrosis and an interface dermatitis, but the presence of targetoid lesions on the palms prompted the diagnosis of photodistributed EM and SJS in both cases.^9,10 Unique to the SJS case was oral involvement.⁹

Distinguishing between a phototoxic reaction and photodistributed EM or SJS may be inconsequential if both can be prevented with photoprotection. Rechallenging patients with vandetanib while practicing photoprotection would help to clarify the mechanism, though this course is not always practical.

Mechanism of Action
As seen in our case series, cutaneous reactions occurred only on sun-exposed surfaces, and patients presented with sharp cutoff points that spared non–sun-exposed areas. Although clinically organized as a subtype of photosensitivity, the phototoxicity mechanism of action is considered a direct toxic effect on keratinocytes, which explains the histopathologic finding of dyskeratotic cells and the clinical spectrum of sunburn reaction, phototoxic EM, and SJS. UVA1 induces 2 photoproducts of vandetanib via a UVA1-mediated debromination process,¹⁷ but these photoproducts are not responsible for epidermal dyskeratosis.¹⁸ It was subsequently demonstrated that keratinocyte death was induced by apoptosis through photoinduced DNA cleavage and the formation of an aryl radical, which can induce further DNA damage.¹⁸ Caro-Gutierrez et al¹⁰ demonstrated a lowered minimal erythema dose in their patient with vandetanib-induced phototoxic EM.

Conversely, photoallergic reactions are considered immune-mediated delayed-type hypersensitivity reactions.^4,7,11 Although the mechanism of a photoallergic reaction remains unclear, it is possible that vandetanib or a metabolite (in susceptible patients) induces an immune-mediated delayed-type hypersensitivity reaction with repeated exposure to the compound, which may explain the varied timing of photoallergic onset, including the events featured in the Bota et al¹¹ case that occurred several months after drug initiation.

Conclusion

Considering the high prevalence of cutaneous AEs, especially varied photosensitivity reactions, these cases emphasize the importance of sun protection to help prevent dose reduction or drug cessation among patients taking vandetanib therapy.

No celeb cheese, please

You don’t mess with cheese. Cheese is love, cheese is life. But now, science has gone too far by bridging the gap between man and cheese.

fotek/iStock/Getty Images Plus

In a new London art exhibit, a biologist and an artist teamed up to create different types of cheese made from … British celebs? Look, we love the Spice Girls as much as the next person, but that doesn’t mean we want Baby Spice Brie.

Bacteria taken from their face, armpits, ears, and even bellybuttons were used to create cheddar, Cheshire, and Stilton cheeses, among others. Yum. The goal of the (possibly blasphemous) exhibit is to change people’s view of microbes and demonstrate how they are essential to human existence. The cheesy contributors included Ruby Tandoh from the Great British Bake Off, chef Heston Blumenthal, and Blur bassist Alex James.

The artists and scientists involved did not yet determine if the cheese was safe for human consumption – not that anyone would eat them, anyway.
 

A poop oops

I’m sure we’ve all been in the position – you’re on your porcelain throne, things aren’t going your way. You’re praying to any and every deity under the sun to get things moving. Maybe you start bargaining … but would you give up a decade’s worth of memories to jump-start your intestines?

wildpixel/iStock/Getty Images Plus

One woman in China seems to have made this deal with the devil. After straining a bit too hard during a nasty bout of constipation, the Hong Kong woman emerged from the bathroom displaying signs of amnesia. Her family quickly discovered she could not remember anything from the past 10 years and took her to the hospital, where she was diagnosed with transient global amnesia. The temporary amnesia was caused by an increase in abdominal and intracerebral pressure that limited oxygen flow to her brain.

The woman regained her memories after about 8 hours and had no recollection of the unfortunate series of events. Or so she claims. We imagine she might remember a bit and is going to start stocking up on prune juice from now on.
 

Juicy, red, and ready to save the world

The Avengers may have finally stopped Thanos, but what could they do against Escherichia coli? And Superman may be more powerful than a locomotive, but could he take on Pseudomonas aeruginosa?

gaus-nataliya/iStock/Getty Images Plus

In this week’s episode of Bacteria vs. the World, we meet the superhero the world really needs.

The humble cranberry doesn’t have super speed or an armored flying exoskeleton, but it does have the power to help antibiotics fight the bacterial menace, as researchers at McGill University and Institut National de la Recherche Scientifique, both in Montreal, discovered.

They found that bacteria exposed to a cranberry extract known as proanthocyanidin had increased sensitivity to antibiotics. The extract, it appears, makes bacterial cell walls more permeable to antibiotics and interferes with the pump mechanism that bacteria use to rid themselves of the drugs. “The antibiotic penetrates more easily, and the bacteria have a harder time getting rid of it,” so the drug is effective at a lower dose, they explained.

But wait, there’s more! “When we simultaneously treated the bacteria with an antibiotic and the cranberry extract, no resistance developed. We were very surprised by this,” lead author Nathalie Tufenkji, PhD, said in a written statement.

This is all great news, of course, but we’re a little surprised by their surprise. Here’s why: The scientific name of the American cranberry is Vaccinium macrocarpon. Vaccinium? Coincidence? We think not.
 

Who needs oncologists anyway?

We’re no strangers to gross-out stories here at Livin’ on the MDedge, but fair warning: This is really up there on the gross-ometer. You may want to brace yourselves.

klebercordeiro/iStock/Getty Images Plus

As with so many good stories, our tale begins with a drunk man vomiting. The 63-year-old man from China had been feeling some discomfort in his throat for some time, especially when eating, but had, up to that point, ignored it. But as the man voided the evening’s mistakes back up to where they came from, something in his throat came loose. Specifically, a meatball-like mass that the man would later describe as a “long, forked tongue.”

Thinking as only a drunk man could, our intrepid friend decided that this object was an integral part of his body and that the best course of action would be to find a glass of water and swallow the mass. However, he did follow this flash of brilliance with an actual good decision, checking himself into the nearest hospital.

As the doctors were examining the man, they discovered the cherry on top of this disgusting story: He’d actually barfed up a tumor. Specifically, a large fibroma, measuring 15 cm by 4 cm, that had taken up residence in the man’s throat. If it hadn’t come out, the fibroma could have continued to grow, potentially obstructing the man’s ability to breathe.

While we’re glad things worked out for our inebriated friend, we’d like to recommend a trip to the doctor for anyone currently having mysterious difficulty swallowing. Don’t make us read about more people throwing up parts of their body. Please.

No celeb cheese, please

You don’t mess with cheese. Cheese is love, cheese is life. But now, science has gone too far by bridging the gap between man and cheese.

fotek/iStock/Getty Images Plus

In a new London art exhibit, a biologist and an artist teamed up to create different types of cheese made from … British celebs? Look, we love the Spice Girls as much as the next person, but that doesn’t mean we want Baby Spice Brie.

Bacteria taken from their face, armpits, ears, and even bellybuttons were used to create cheddar, Cheshire, and Stilton cheeses, among others. Yum. The goal of the (possibly blasphemous) exhibit is to change people’s view of microbes and demonstrate how they are essential to human existence. The cheesy contributors included Ruby Tandoh from the Great British Bake Off, chef Heston Blumenthal, and Blur bassist Alex James.

The artists and scientists involved did not yet determine if the cheese was safe for human consumption – not that anyone would eat them, anyway.
 

A poop oops

I’m sure we’ve all been in the position – you’re on your porcelain throne, things aren’t going your way. You’re praying to any and every deity under the sun to get things moving. Maybe you start bargaining … but would you give up a decade’s worth of memories to jump-start your intestines?

wildpixel/iStock/Getty Images Plus

One woman in China seems to have made this deal with the devil. After straining a bit too hard during a nasty bout of constipation, the Hong Kong woman emerged from the bathroom displaying signs of amnesia. Her family quickly discovered she could not remember anything from the past 10 years and took her to the hospital, where she was diagnosed with transient global amnesia. The temporary amnesia was caused by an increase in abdominal and intracerebral pressure that limited oxygen flow to her brain.

The woman regained her memories after about 8 hours and had no recollection of the unfortunate series of events. Or so she claims. We imagine she might remember a bit and is going to start stocking up on prune juice from now on.
 

Juicy, red, and ready to save the world

The Avengers may have finally stopped Thanos, but what could they do against Escherichia coli? And Superman may be more powerful than a locomotive, but could he take on Pseudomonas aeruginosa?

gaus-nataliya/iStock/Getty Images Plus

In this week’s episode of Bacteria vs. the World, we meet the superhero the world really needs.

The humble cranberry doesn’t have super speed or an armored flying exoskeleton, but it does have the power to help antibiotics fight the bacterial menace, as researchers at McGill University and Institut National de la Recherche Scientifique, both in Montreal, discovered.

They found that bacteria exposed to a cranberry extract known as proanthocyanidin had increased sensitivity to antibiotics. The extract, it appears, makes bacterial cell walls more permeable to antibiotics and interferes with the pump mechanism that bacteria use to rid themselves of the drugs. “The antibiotic penetrates more easily, and the bacteria have a harder time getting rid of it,” so the drug is effective at a lower dose, they explained.

But wait, there’s more! “When we simultaneously treated the bacteria with an antibiotic and the cranberry extract, no resistance developed. We were very surprised by this,” lead author Nathalie Tufenkji, PhD, said in a written statement.

This is all great news, of course, but we’re a little surprised by their surprise. Here’s why: The scientific name of the American cranberry is Vaccinium macrocarpon. Vaccinium? Coincidence? We think not.
 

Who needs oncologists anyway?

We’re no strangers to gross-out stories here at Livin’ on the MDedge, but fair warning: This is really up there on the gross-ometer. You may want to brace yourselves.

klebercordeiro/iStock/Getty Images Plus

As with so many good stories, our tale begins with a drunk man vomiting. The 63-year-old man from China had been feeling some discomfort in his throat for some time, especially when eating, but had, up to that point, ignored it. But as the man voided the evening’s mistakes back up to where they came from, something in his throat came loose. Specifically, a meatball-like mass that the man would later describe as a “long, forked tongue.”

Thinking as only a drunk man could, our intrepid friend decided that this object was an integral part of his body and that the best course of action would be to find a glass of water and swallow the mass. However, he did follow this flash of brilliance with an actual good decision, checking himself into the nearest hospital.

As the doctors were examining the man, they discovered the cherry on top of this disgusting story: He’d actually barfed up a tumor. Specifically, a large fibroma, measuring 15 cm by 4 cm, that had taken up residence in the man’s throat. If it hadn’t come out, the fibroma could have continued to grow, potentially obstructing the man’s ability to breathe.

While we’re glad things worked out for our inebriated friend, we’d like to recommend a trip to the doctor for anyone currently having mysterious difficulty swallowing. Don’t make us read about more people throwing up parts of their body. Please.

No celeb cheese, please

You don’t mess with cheese. Cheese is love, cheese is life. But now, science has gone too far by bridging the gap between man and cheese.

fotek/iStock/Getty Images Plus

In a new London art exhibit, a biologist and an artist teamed up to create different types of cheese made from … British celebs? Look, we love the Spice Girls as much as the next person, but that doesn’t mean we want Baby Spice Brie.

Bacteria taken from their face, armpits, ears, and even bellybuttons were used to create cheddar, Cheshire, and Stilton cheeses, among others. Yum. The goal of the (possibly blasphemous) exhibit is to change people’s view of microbes and demonstrate how they are essential to human existence. The cheesy contributors included Ruby Tandoh from the Great British Bake Off, chef Heston Blumenthal, and Blur bassist Alex James.

The artists and scientists involved did not yet determine if the cheese was safe for human consumption – not that anyone would eat them, anyway.
 

A poop oops

I’m sure we’ve all been in the position – you’re on your porcelain throne, things aren’t going your way. You’re praying to any and every deity under the sun to get things moving. Maybe you start bargaining … but would you give up a decade’s worth of memories to jump-start your intestines?

wildpixel/iStock/Getty Images Plus

One woman in China seems to have made this deal with the devil. After straining a bit too hard during a nasty bout of constipation, the Hong Kong woman emerged from the bathroom displaying signs of amnesia. Her family quickly discovered she could not remember anything from the past 10 years and took her to the hospital, where she was diagnosed with transient global amnesia. The temporary amnesia was caused by an increase in abdominal and intracerebral pressure that limited oxygen flow to her brain.

The woman regained her memories after about 8 hours and had no recollection of the unfortunate series of events. Or so she claims. We imagine she might remember a bit and is going to start stocking up on prune juice from now on.
 

Juicy, red, and ready to save the world

The Avengers may have finally stopped Thanos, but what could they do against Escherichia coli? And Superman may be more powerful than a locomotive, but could he take on Pseudomonas aeruginosa?

gaus-nataliya/iStock/Getty Images Plus

In this week’s episode of Bacteria vs. the World, we meet the superhero the world really needs.

The humble cranberry doesn’t have super speed or an armored flying exoskeleton, but it does have the power to help antibiotics fight the bacterial menace, as researchers at McGill University and Institut National de la Recherche Scientifique, both in Montreal, discovered.

They found that bacteria exposed to a cranberry extract known as proanthocyanidin had increased sensitivity to antibiotics. The extract, it appears, makes bacterial cell walls more permeable to antibiotics and interferes with the pump mechanism that bacteria use to rid themselves of the drugs. “The antibiotic penetrates more easily, and the bacteria have a harder time getting rid of it,” so the drug is effective at a lower dose, they explained.

But wait, there’s more! “When we simultaneously treated the bacteria with an antibiotic and the cranberry extract, no resistance developed. We were very surprised by this,” lead author Nathalie Tufenkji, PhD, said in a written statement.

This is all great news, of course, but we’re a little surprised by their surprise. Here’s why: The scientific name of the American cranberry is Vaccinium macrocarpon. Vaccinium? Coincidence? We think not.
 

Who needs oncologists anyway?

We’re no strangers to gross-out stories here at Livin’ on the MDedge, but fair warning: This is really up there on the gross-ometer. You may want to brace yourselves.

klebercordeiro/iStock/Getty Images Plus

As with so many good stories, our tale begins with a drunk man vomiting. The 63-year-old man from China had been feeling some discomfort in his throat for some time, especially when eating, but had, up to that point, ignored it. But as the man voided the evening’s mistakes back up to where they came from, something in his throat came loose. Specifically, a meatball-like mass that the man would later describe as a “long, forked tongue.”

Thinking as only a drunk man could, our intrepid friend decided that this object was an integral part of his body and that the best course of action would be to find a glass of water and swallow the mass. However, he did follow this flash of brilliance with an actual good decision, checking himself into the nearest hospital.

As the doctors were examining the man, they discovered the cherry on top of this disgusting story: He’d actually barfed up a tumor. Specifically, a large fibroma, measuring 15 cm by 4 cm, that had taken up residence in the man’s throat. If it hadn’t come out, the fibroma could have continued to grow, potentially obstructing the man’s ability to breathe.

While we’re glad things worked out for our inebriated friend, we’d like to recommend a trip to the doctor for anyone currently having mysterious difficulty swallowing. Don’t make us read about more people throwing up parts of their body. Please.

For adults with Crohn’s disease in remission at baseline, eating red and processed meat no more than once per month did not reduce risk of relapse in a randomized control trial.

Fuse/Thinkstock

After 49 weeks, there were no significant differences in time to relapse, time to moderate or severe relapse, or time to persistent relapse between the low- and high-meat groups, reported Lindsey G. Aldenberg, DO, of the Children’s Hospital of Philadelphia and coinvestigators. The findings were published in Gastroenterology.

The randomized study included 213 adults with Crohn’s disease whose short Crohn’s Disease Activity Index (sCDAI) score was 150 or less at baseline and who consumed red meat at least once weekly. They were instructed to consume one serving (3 ounces) of red meat or any processed (smoked, salted, or otherwise preserved) meat at least twice weekly (high-meat group) or no more than once monthly (low-meat group). To create a placebo-like effect, all patients were told to drink at least 16 ounces of water daily. Each week, patients were emailed a web-based survey of disease status and dietary adherence. At baseline and during six other weeks, they also received a daily survey of disease activity and current medications. The primary outcome was symptomatic relapse, defined as at least a 70-point rise such that sCDAI score exceeded 150, surgery for Crohn’s disease flare, or self-reported initiation or dose increase of mesalamine, thiopurine, methotrexate, corticosteroid, anti–tumor necrosis factor-alpha therapy, or natalizumab.

In all, 78% (166) of patients either completed the study or experienced an outcome. Symptomatic relapse occurred in 62% of these 166 patients, while 42% and 35% had moderate to severe or persistent relapses, respectively. “There were no significant differences in time to relapse for any of the outcomes (P greater than .3 for all outcomes),” the researchers wrote. Results were similar when they assumed that patients who completed no surveys all relapsed at week 1.

At week 20, median fecal calprotectin levels were higher in the high-meat arm (74.5 mcg/g) than in the low-meat arm (36.0 mcg/g), but the difference was not statistically significant. Proportions of patients with fecal calprotectin levels above 150 or 250 mcg/g also did not significantly differ between arms.

Adherence to the diets was reasonable: Patients in the high-meat group reported consuming at least two servings of red or processed meat during 98.5% of weeks, while patients in the low-meat arm completely abstained from red or processed meat during 57.3% of weeks. A logistic regression model showed that the high-meat group was much more likely to consume a least two servings of red or processed meat in the prior week than the low-meat group (P less than .0001). Approximately 90% of patients in both arms drank the recommended amount of water.

Study participants were part of IBD Partners, an Internet-based cohort of more than 15,000 patients with inflammatory bowel disease. Recruitment into the trial occurred through emails, social media, educational and fundraising events, and the Crohn’s & Colitis Foundation website, the researchers said.

“Based on these results, there is insufficient evidence to recommend reduction of red and processed meat consumption solely for the purpose of improving Crohn’s disease outcomes, although there may be some benefit for other health conditions,” Dr. Aldenberg and associates concluded.

The Crohn’s and Colitis Foundation and the National Institutes of Health supported the work. Dr. Aldenberg disclosed receiving research funding from Seres Therapeutics. Two of six coinvestigators disclosed ties to Nestle Health Science, AbbVie, Pfizer, Eli Lilly, and several other pharmaceutical companies.

SOURCE: Aldenberg L et al. Gastroenterology. 2019 Mar 11. doi: 10.1053/j.gastro.2019.03.01.

For adults with Crohn’s disease in remission at baseline, eating red and processed meat no more than once per month did not reduce risk of relapse in a randomized control trial.

Fuse/Thinkstock

After 49 weeks, there were no significant differences in time to relapse, time to moderate or severe relapse, or time to persistent relapse between the low- and high-meat groups, reported Lindsey G. Aldenberg, DO, of the Children’s Hospital of Philadelphia and coinvestigators. The findings were published in Gastroenterology.

The randomized study included 213 adults with Crohn’s disease whose short Crohn’s Disease Activity Index (sCDAI) score was 150 or less at baseline and who consumed red meat at least once weekly. They were instructed to consume one serving (3 ounces) of red meat or any processed (smoked, salted, or otherwise preserved) meat at least twice weekly (high-meat group) or no more than once monthly (low-meat group). To create a placebo-like effect, all patients were told to drink at least 16 ounces of water daily. Each week, patients were emailed a web-based survey of disease status and dietary adherence. At baseline and during six other weeks, they also received a daily survey of disease activity and current medications. The primary outcome was symptomatic relapse, defined as at least a 70-point rise such that sCDAI score exceeded 150, surgery for Crohn’s disease flare, or self-reported initiation or dose increase of mesalamine, thiopurine, methotrexate, corticosteroid, anti–tumor necrosis factor-alpha therapy, or natalizumab.

In all, 78% (166) of patients either completed the study or experienced an outcome. Symptomatic relapse occurred in 62% of these 166 patients, while 42% and 35% had moderate to severe or persistent relapses, respectively. “There were no significant differences in time to relapse for any of the outcomes (P greater than .3 for all outcomes),” the researchers wrote. Results were similar when they assumed that patients who completed no surveys all relapsed at week 1.

At week 20, median fecal calprotectin levels were higher in the high-meat arm (74.5 mcg/g) than in the low-meat arm (36.0 mcg/g), but the difference was not statistically significant. Proportions of patients with fecal calprotectin levels above 150 or 250 mcg/g also did not significantly differ between arms.

Adherence to the diets was reasonable: Patients in the high-meat group reported consuming at least two servings of red or processed meat during 98.5% of weeks, while patients in the low-meat arm completely abstained from red or processed meat during 57.3% of weeks. A logistic regression model showed that the high-meat group was much more likely to consume a least two servings of red or processed meat in the prior week than the low-meat group (P less than .0001). Approximately 90% of patients in both arms drank the recommended amount of water.

Study participants were part of IBD Partners, an Internet-based cohort of more than 15,000 patients with inflammatory bowel disease. Recruitment into the trial occurred through emails, social media, educational and fundraising events, and the Crohn’s & Colitis Foundation website, the researchers said.

“Based on these results, there is insufficient evidence to recommend reduction of red and processed meat consumption solely for the purpose of improving Crohn’s disease outcomes, although there may be some benefit for other health conditions,” Dr. Aldenberg and associates concluded.

The Crohn’s and Colitis Foundation and the National Institutes of Health supported the work. Dr. Aldenberg disclosed receiving research funding from Seres Therapeutics. Two of six coinvestigators disclosed ties to Nestle Health Science, AbbVie, Pfizer, Eli Lilly, and several other pharmaceutical companies.

SOURCE: Aldenberg L et al. Gastroenterology. 2019 Mar 11. doi: 10.1053/j.gastro.2019.03.01.

For adults with Crohn’s disease in remission at baseline, eating red and processed meat no more than once per month did not reduce risk of relapse in a randomized control trial.

Fuse/Thinkstock

After 49 weeks, there were no significant differences in time to relapse, time to moderate or severe relapse, or time to persistent relapse between the low- and high-meat groups, reported Lindsey G. Aldenberg, DO, of the Children’s Hospital of Philadelphia and coinvestigators. The findings were published in Gastroenterology.

The randomized study included 213 adults with Crohn’s disease whose short Crohn’s Disease Activity Index (sCDAI) score was 150 or less at baseline and who consumed red meat at least once weekly. They were instructed to consume one serving (3 ounces) of red meat or any processed (smoked, salted, or otherwise preserved) meat at least twice weekly (high-meat group) or no more than once monthly (low-meat group). To create a placebo-like effect, all patients were told to drink at least 16 ounces of water daily. Each week, patients were emailed a web-based survey of disease status and dietary adherence. At baseline and during six other weeks, they also received a daily survey of disease activity and current medications. The primary outcome was symptomatic relapse, defined as at least a 70-point rise such that sCDAI score exceeded 150, surgery for Crohn’s disease flare, or self-reported initiation or dose increase of mesalamine, thiopurine, methotrexate, corticosteroid, anti–tumor necrosis factor-alpha therapy, or natalizumab.

In all, 78% (166) of patients either completed the study or experienced an outcome. Symptomatic relapse occurred in 62% of these 166 patients, while 42% and 35% had moderate to severe or persistent relapses, respectively. “There were no significant differences in time to relapse for any of the outcomes (P greater than .3 for all outcomes),” the researchers wrote. Results were similar when they assumed that patients who completed no surveys all relapsed at week 1.

At week 20, median fecal calprotectin levels were higher in the high-meat arm (74.5 mcg/g) than in the low-meat arm (36.0 mcg/g), but the difference was not statistically significant. Proportions of patients with fecal calprotectin levels above 150 or 250 mcg/g also did not significantly differ between arms.

Adherence to the diets was reasonable: Patients in the high-meat group reported consuming at least two servings of red or processed meat during 98.5% of weeks, while patients in the low-meat arm completely abstained from red or processed meat during 57.3% of weeks. A logistic regression model showed that the high-meat group was much more likely to consume a least two servings of red or processed meat in the prior week than the low-meat group (P less than .0001). Approximately 90% of patients in both arms drank the recommended amount of water.

Study participants were part of IBD Partners, an Internet-based cohort of more than 15,000 patients with inflammatory bowel disease. Recruitment into the trial occurred through emails, social media, educational and fundraising events, and the Crohn’s & Colitis Foundation website, the researchers said.

“Based on these results, there is insufficient evidence to recommend reduction of red and processed meat consumption solely for the purpose of improving Crohn’s disease outcomes, although there may be some benefit for other health conditions,” Dr. Aldenberg and associates concluded.

The Crohn’s and Colitis Foundation and the National Institutes of Health supported the work. Dr. Aldenberg disclosed receiving research funding from Seres Therapeutics. Two of six coinvestigators disclosed ties to Nestle Health Science, AbbVie, Pfizer, Eli Lilly, and several other pharmaceutical companies.

SOURCE: Aldenberg L et al. Gastroenterology. 2019 Mar 11. doi: 10.1053/j.gastro.2019.03.01.

A 10-valent pneumococcal conjugate vaccine appeared equally effective against pneumococcal disease in boys and girls, according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.

MarianVejcik/Getty Images

For the study, published in Vaccine, the investigators conducted a post hoc analysis of the phase III/IV, cluster-randomized, double-blind FinIP trial, in which more than 30,000 infants received the PHiD-CV10 vaccine or a placebo. Patients were aged less than 7 months when they received their first vaccination, and received two or three primary doses, plus a booster shot after the age of 11 months (Vaccine. 2019 May 20. doi: 10.1016/j.vaccine.2019.05.033).

In term infants, vaccine effectiveness was similar in boys and girls; while the vaccine worked marginally better in girls, the difference was not significant. Infants who received the 2 + 1 schedule had vaccine effectiveness similar to that of those who received the 3 + 1 schedule. In a smaller subanalysis of 1,519 preterm infants, outcomes of pneumonia were more common, but the vaccine seemed to confer protection, although the sample size was not large enough for statistical significance to be reached.

“The point estimates of vaccine effectiveness suggest protection in both sexes, and also among the preterm and low-birth-weight infants. ... There were no significant differences between the 2 + 1 and 3 + 1 schedules in any of the subgroups analyzed. Based on this study, the 2 + 1 or “Nordic” schedule is sufficient also for the risk groups such as the preterm or low-birth-weight infants,” the investigators concluded.

Five study authors are employees of the National Institute for Health and Welfare, which received funding for the study from GlaxoSmithKline. Four coauthors are employees of GlaxoSmithKline; three of them own shares in the company.

[email protected]

A 10-valent pneumococcal conjugate vaccine appeared equally effective against pneumococcal disease in boys and girls, according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.

MarianVejcik/Getty Images

For the study, published in Vaccine, the investigators conducted a post hoc analysis of the phase III/IV, cluster-randomized, double-blind FinIP trial, in which more than 30,000 infants received the PHiD-CV10 vaccine or a placebo. Patients were aged less than 7 months when they received their first vaccination, and received two or three primary doses, plus a booster shot after the age of 11 months (Vaccine. 2019 May 20. doi: 10.1016/j.vaccine.2019.05.033).

In term infants, vaccine effectiveness was similar in boys and girls; while the vaccine worked marginally better in girls, the difference was not significant. Infants who received the 2 + 1 schedule had vaccine effectiveness similar to that of those who received the 3 + 1 schedule. In a smaller subanalysis of 1,519 preterm infants, outcomes of pneumonia were more common, but the vaccine seemed to confer protection, although the sample size was not large enough for statistical significance to be reached.

“The point estimates of vaccine effectiveness suggest protection in both sexes, and also among the preterm and low-birth-weight infants. ... There were no significant differences between the 2 + 1 and 3 + 1 schedules in any of the subgroups analyzed. Based on this study, the 2 + 1 or “Nordic” schedule is sufficient also for the risk groups such as the preterm or low-birth-weight infants,” the investigators concluded.

Five study authors are employees of the National Institute for Health and Welfare, which received funding for the study from GlaxoSmithKline. Four coauthors are employees of GlaxoSmithKline; three of them own shares in the company.

[email protected]

A 10-valent pneumococcal conjugate vaccine appeared equally effective against pneumococcal disease in boys and girls, according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.

MarianVejcik/Getty Images

For the study, published in Vaccine, the investigators conducted a post hoc analysis of the phase III/IV, cluster-randomized, double-blind FinIP trial, in which more than 30,000 infants received the PHiD-CV10 vaccine or a placebo. Patients were aged less than 7 months when they received their first vaccination, and received two or three primary doses, plus a booster shot after the age of 11 months (Vaccine. 2019 May 20. doi: 10.1016/j.vaccine.2019.05.033).

In term infants, vaccine effectiveness was similar in boys and girls; while the vaccine worked marginally better in girls, the difference was not significant. Infants who received the 2 + 1 schedule had vaccine effectiveness similar to that of those who received the 3 + 1 schedule. In a smaller subanalysis of 1,519 preterm infants, outcomes of pneumonia were more common, but the vaccine seemed to confer protection, although the sample size was not large enough for statistical significance to be reached.

“The point estimates of vaccine effectiveness suggest protection in both sexes, and also among the preterm and low-birth-weight infants. ... There were no significant differences between the 2 + 1 and 3 + 1 schedules in any of the subgroups analyzed. Based on this study, the 2 + 1 or “Nordic” schedule is sufficient also for the risk groups such as the preterm or low-birth-weight infants,” the investigators concluded.

Five study authors are employees of the National Institute for Health and Welfare, which received funding for the study from GlaxoSmithKline. Four coauthors are employees of GlaxoSmithKline; three of them own shares in the company.

[email protected]

CHICAGO – Once thought to be a rare disease and largely neglected as a focus of research, hidradenitis suppurativa (HS) is now the target of more research funding that is expected to lead to better treatments and increase the number of patients seeking care, according to an expert interview conducted at the annual meeting of the Society for Investigational Dermatology.

“For decades ... we’ve really not understood how prevalent it is,” said Haley B. Naik, MD, of the department of dermatology at University of California, San Francisco, in a video interview. “Now, thanks to great population-based studies and new data, we know that HS is common and hugely impacts the lives of the people who suffer with this condition.”

Recapping some of the highlights of an update on this chronic inflammatory skin condition that she presented at the meeting, Dr. Naik said that HS has been mischaracterized as rare. Many patients, embarrassed by the symptoms or failing to receive adequate relief from previous health care encounters, are not currently seeking care.

This will change as treatments improve, according to Dr. Naik, who asserted that HS has become a hot topic. Progress in understanding the underlying pathophysiology has been driving new management strategies. She counted more than 15 clinical trials being conducted with new agents for this disease in a clinicaltrials.gov survey.

In the interview, Dr. Naik calls on dermatologists to increase their awareness of the signs and symptoms of HS so that they can diagnose and intervene earlier, a step that will be made easier as new therapies become available.

CHICAGO – Once thought to be a rare disease and largely neglected as a focus of research, hidradenitis suppurativa (HS) is now the target of more research funding that is expected to lead to better treatments and increase the number of patients seeking care, according to an expert interview conducted at the annual meeting of the Society for Investigational Dermatology.

“For decades ... we’ve really not understood how prevalent it is,” said Haley B. Naik, MD, of the department of dermatology at University of California, San Francisco, in a video interview. “Now, thanks to great population-based studies and new data, we know that HS is common and hugely impacts the lives of the people who suffer with this condition.”

Recapping some of the highlights of an update on this chronic inflammatory skin condition that she presented at the meeting, Dr. Naik said that HS has been mischaracterized as rare. Many patients, embarrassed by the symptoms or failing to receive adequate relief from previous health care encounters, are not currently seeking care.

This will change as treatments improve, according to Dr. Naik, who asserted that HS has become a hot topic. Progress in understanding the underlying pathophysiology has been driving new management strategies. She counted more than 15 clinical trials being conducted with new agents for this disease in a clinicaltrials.gov survey.

In the interview, Dr. Naik calls on dermatologists to increase their awareness of the signs and symptoms of HS so that they can diagnose and intervene earlier, a step that will be made easier as new therapies become available.

CHICAGO – Once thought to be a rare disease and largely neglected as a focus of research, hidradenitis suppurativa (HS) is now the target of more research funding that is expected to lead to better treatments and increase the number of patients seeking care, according to an expert interview conducted at the annual meeting of the Society for Investigational Dermatology.

“For decades ... we’ve really not understood how prevalent it is,” said Haley B. Naik, MD, of the department of dermatology at University of California, San Francisco, in a video interview. “Now, thanks to great population-based studies and new data, we know that HS is common and hugely impacts the lives of the people who suffer with this condition.”

Recapping some of the highlights of an update on this chronic inflammatory skin condition that she presented at the meeting, Dr. Naik said that HS has been mischaracterized as rare. Many patients, embarrassed by the symptoms or failing to receive adequate relief from previous health care encounters, are not currently seeking care.

This will change as treatments improve, according to Dr. Naik, who asserted that HS has become a hot topic. Progress in understanding the underlying pathophysiology has been driving new management strategies. She counted more than 15 clinical trials being conducted with new agents for this disease in a clinicaltrials.gov survey.

In the interview, Dr. Naik calls on dermatologists to increase their awareness of the signs and symptoms of HS so that they can diagnose and intervene earlier, a step that will be made easier as new therapies become available.