MDedge Dermatology

Patients with recalcitrant hidradenitis suppurativa (HS) who self-administered intravenous ertapenem for an average of 13 weeks experienced improvements in clinical and inflammatory markers, and expressed satisfaction at the completion of treatment, a retrospective study showed.

“These findings suggest a course of 12 to 16 weeks of ertapenem may be appropriate as a new standard length of therapy in HS patients, which is at least twice the current recommendation of the North American treatment guidelines,” wrote corresponding author Steven R. Cohen, MD, MPH, of the departments of dermatology at Weill Cornell Medicine and Albert Einstein College of Medicine, New York, and his coauthors. The results were published online February 14, 2024, in JAMA Dermatology.

In an earlier study , some of the same researchers evaluated the efficacy of daily IV ertapenem for 6 weeks in seven patients with HS. The patients experienced “notable remediation of disease that was rapidly lost within 1 month of withdrawal.”

Elsevier

Key outcome measures of interest were the HS Physician Global Assessment (PGA) score (a 6-point scale ranging from clear to very severe) and a numerical rating scale (NRS) for pain (an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain) and markers of inflammation such as leukocytes, erythrocyte sedimentation rate, C-reactive protein (CRP), and interleukin (IL)-6. The researchers measured these outcomes at baseline, the midcourse of IV ertapenem treatment, at the end of the course, and post therapy.

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

The mean age of the patients was 35.8 years, 62.2% were female, and 60.2% were Black. The mean treatment duration was 13.1 weeks and the mean posttherapy follow-up occurred after a mean of 7.8 weeks.

Between baseline and posttherapy follow-up, the HS PGA scores dropped from a mean of 3.9 to 2.7 and the NRS for pain dropped from 4.2 to 1.8 (P < .001 for both associations). Markers of inflammation also dropped between baseline and post therapy.

Specifically, values for CRP dropped from 5.4 to 2.4 mg/dL; IL-6 dropped from 25.2 to 13.7, and leukocytes dropped from 11.3 to 10.0 (P < .001 for all associations). Among the 76 patients who participated in a follow-up telephone survey, 63 (80.3%) reported medium to high satisfaction with their course of ertapenem, and 69 (90.8%) said they would recommend the treatment to other patients with HS.

The authors noted certain limitations of their study, including its retrospective, single-center design, the lack of a control group, and the fact that the HS-PGA scores at each visit did not meet the threshold of a 2-point decrease that is considered a clinically meaningful in the medical literature.

The definitive mechanism of ertapenem efficacy remains elusive, the authors pointed out. “Although oral antibiotics are generally accepted as a core therapeutic approach to HS, much less is known about the efficacy of IV antibiotics, especially ertapenem, a parenteral carbapenem possessing activity against many gram-positive bacteria, gram-negative bacteria, and anaerobic organisms,” they wrote.

In an accompanying editorial, Haley B. Naik, MD, MHSc, a dermatologist at the University of California, San Francisco, said that adopting prolonged courses of ertapenem treatment “comes with substantial individual and public health considerations”.

Courtesy Dr. Naik

“Even though HS is a noninfectious disease, microbes might play a role in inciting HS immune dysregulation, prompting the inclusion of antimicrobial therapy in treatment regimens. However, broad-spectrum antibiotics for HS are associated with high levels of antibiotic resistance,” she wrote. Prolonged use of ertapenem and other carbapenems in HS treatment “will likely increase antimicrobial resistance, thereby limiting management of both HS and comorbid infections.”

Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, who was asked to comment on the study, said that, despite significant advances in the management of HS over the past decade, there are still patients who do not respond adequately to standard treatments.

For these patients, IV ertapenem can serve as a valuable bridge to a longer-term therapeutic option, “be it surgery or escalated immunomodulation,” such as dual biologic therapy, she said. “In my personal experience, IV ertapenem, which like the authors I also typically use for a 12-week course, delivers impressive and fast results even in the worst disease cases.

“It can be difficult to maintain the therapeutic benefit of ertapenem after it is discontinued, which is why patients should be on concomitant medications as they were in this study and have a post-ertapenem treatment plan in place,” said Dr. Hsiao, who was not involved with the study. “Hopefully, we will be able to one day understand why ertapenem is so effective for HS and be able to harness that benefit for patients without concern for antimicrobial resistance.”

Dr. Cohen reported receiving personal fees from Verrica Pharmaceuticals and belonging to the Board of Trustees of the American Skin Association outside the submitted work. No other disclosures were reported. Dr. Naik reported having received grants from AbbVie and the National Institutes of Health; personal fees from Novartis, UCB, Boehringer Ingelheim, 23andMe, Aristea Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, and Pfizer; and shares from Radera during the conduct of the study. She is a board member of the Hidradenitis Suppurativa Foundation. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, UCB, as a speaker for AbbVie, Novartis, and UCB, and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

Patients with recalcitrant hidradenitis suppurativa (HS) who self-administered intravenous ertapenem for an average of 13 weeks experienced improvements in clinical and inflammatory markers, and expressed satisfaction at the completion of treatment, a retrospective study showed.

“These findings suggest a course of 12 to 16 weeks of ertapenem may be appropriate as a new standard length of therapy in HS patients, which is at least twice the current recommendation of the North American treatment guidelines,” wrote corresponding author Steven R. Cohen, MD, MPH, of the departments of dermatology at Weill Cornell Medicine and Albert Einstein College of Medicine, New York, and his coauthors. The results were published online February 14, 2024, in JAMA Dermatology.

In an earlier study , some of the same researchers evaluated the efficacy of daily IV ertapenem for 6 weeks in seven patients with HS. The patients experienced “notable remediation of disease that was rapidly lost within 1 month of withdrawal.”

Elsevier

Key outcome measures of interest were the HS Physician Global Assessment (PGA) score (a 6-point scale ranging from clear to very severe) and a numerical rating scale (NRS) for pain (an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain) and markers of inflammation such as leukocytes, erythrocyte sedimentation rate, C-reactive protein (CRP), and interleukin (IL)-6. The researchers measured these outcomes at baseline, the midcourse of IV ertapenem treatment, at the end of the course, and post therapy.

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

The mean age of the patients was 35.8 years, 62.2% were female, and 60.2% were Black. The mean treatment duration was 13.1 weeks and the mean posttherapy follow-up occurred after a mean of 7.8 weeks.

Between baseline and posttherapy follow-up, the HS PGA scores dropped from a mean of 3.9 to 2.7 and the NRS for pain dropped from 4.2 to 1.8 (P < .001 for both associations). Markers of inflammation also dropped between baseline and post therapy.

Specifically, values for CRP dropped from 5.4 to 2.4 mg/dL; IL-6 dropped from 25.2 to 13.7, and leukocytes dropped from 11.3 to 10.0 (P < .001 for all associations). Among the 76 patients who participated in a follow-up telephone survey, 63 (80.3%) reported medium to high satisfaction with their course of ertapenem, and 69 (90.8%) said they would recommend the treatment to other patients with HS.

The authors noted certain limitations of their study, including its retrospective, single-center design, the lack of a control group, and the fact that the HS-PGA scores at each visit did not meet the threshold of a 2-point decrease that is considered a clinically meaningful in the medical literature.

The definitive mechanism of ertapenem efficacy remains elusive, the authors pointed out. “Although oral antibiotics are generally accepted as a core therapeutic approach to HS, much less is known about the efficacy of IV antibiotics, especially ertapenem, a parenteral carbapenem possessing activity against many gram-positive bacteria, gram-negative bacteria, and anaerobic organisms,” they wrote.

In an accompanying editorial, Haley B. Naik, MD, MHSc, a dermatologist at the University of California, San Francisco, said that adopting prolonged courses of ertapenem treatment “comes with substantial individual and public health considerations”.

Courtesy Dr. Naik

“Even though HS is a noninfectious disease, microbes might play a role in inciting HS immune dysregulation, prompting the inclusion of antimicrobial therapy in treatment regimens. However, broad-spectrum antibiotics for HS are associated with high levels of antibiotic resistance,” she wrote. Prolonged use of ertapenem and other carbapenems in HS treatment “will likely increase antimicrobial resistance, thereby limiting management of both HS and comorbid infections.”

Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, who was asked to comment on the study, said that, despite significant advances in the management of HS over the past decade, there are still patients who do not respond adequately to standard treatments.

For these patients, IV ertapenem can serve as a valuable bridge to a longer-term therapeutic option, “be it surgery or escalated immunomodulation,” such as dual biologic therapy, she said. “In my personal experience, IV ertapenem, which like the authors I also typically use for a 12-week course, delivers impressive and fast results even in the worst disease cases.

“It can be difficult to maintain the therapeutic benefit of ertapenem after it is discontinued, which is why patients should be on concomitant medications as they were in this study and have a post-ertapenem treatment plan in place,” said Dr. Hsiao, who was not involved with the study. “Hopefully, we will be able to one day understand why ertapenem is so effective for HS and be able to harness that benefit for patients without concern for antimicrobial resistance.”

Dr. Cohen reported receiving personal fees from Verrica Pharmaceuticals and belonging to the Board of Trustees of the American Skin Association outside the submitted work. No other disclosures were reported. Dr. Naik reported having received grants from AbbVie and the National Institutes of Health; personal fees from Novartis, UCB, Boehringer Ingelheim, 23andMe, Aristea Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, and Pfizer; and shares from Radera during the conduct of the study. She is a board member of the Hidradenitis Suppurativa Foundation. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, UCB, as a speaker for AbbVie, Novartis, and UCB, and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

Patients with recalcitrant hidradenitis suppurativa (HS) who self-administered intravenous ertapenem for an average of 13 weeks experienced improvements in clinical and inflammatory markers, and expressed satisfaction at the completion of treatment, a retrospective study showed.

“These findings suggest a course of 12 to 16 weeks of ertapenem may be appropriate as a new standard length of therapy in HS patients, which is at least twice the current recommendation of the North American treatment guidelines,” wrote corresponding author Steven R. Cohen, MD, MPH, of the departments of dermatology at Weill Cornell Medicine and Albert Einstein College of Medicine, New York, and his coauthors. The results were published online February 14, 2024, in JAMA Dermatology.

In an earlier study , some of the same researchers evaluated the efficacy of daily IV ertapenem for 6 weeks in seven patients with HS. The patients experienced “notable remediation of disease that was rapidly lost within 1 month of withdrawal.”

Elsevier

Key outcome measures of interest were the HS Physician Global Assessment (PGA) score (a 6-point scale ranging from clear to very severe) and a numerical rating scale (NRS) for pain (an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain) and markers of inflammation such as leukocytes, erythrocyte sedimentation rate, C-reactive protein (CRP), and interleukin (IL)-6. The researchers measured these outcomes at baseline, the midcourse of IV ertapenem treatment, at the end of the course, and post therapy.

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

The mean age of the patients was 35.8 years, 62.2% were female, and 60.2% were Black. The mean treatment duration was 13.1 weeks and the mean posttherapy follow-up occurred after a mean of 7.8 weeks.

Between baseline and posttherapy follow-up, the HS PGA scores dropped from a mean of 3.9 to 2.7 and the NRS for pain dropped from 4.2 to 1.8 (P < .001 for both associations). Markers of inflammation also dropped between baseline and post therapy.

Specifically, values for CRP dropped from 5.4 to 2.4 mg/dL; IL-6 dropped from 25.2 to 13.7, and leukocytes dropped from 11.3 to 10.0 (P < .001 for all associations). Among the 76 patients who participated in a follow-up telephone survey, 63 (80.3%) reported medium to high satisfaction with their course of ertapenem, and 69 (90.8%) said they would recommend the treatment to other patients with HS.

The authors noted certain limitations of their study, including its retrospective, single-center design, the lack of a control group, and the fact that the HS-PGA scores at each visit did not meet the threshold of a 2-point decrease that is considered a clinically meaningful in the medical literature.

The definitive mechanism of ertapenem efficacy remains elusive, the authors pointed out. “Although oral antibiotics are generally accepted as a core therapeutic approach to HS, much less is known about the efficacy of IV antibiotics, especially ertapenem, a parenteral carbapenem possessing activity against many gram-positive bacteria, gram-negative bacteria, and anaerobic organisms,” they wrote.

In an accompanying editorial, Haley B. Naik, MD, MHSc, a dermatologist at the University of California, San Francisco, said that adopting prolonged courses of ertapenem treatment “comes with substantial individual and public health considerations”.

Courtesy Dr. Naik

“Even though HS is a noninfectious disease, microbes might play a role in inciting HS immune dysregulation, prompting the inclusion of antimicrobial therapy in treatment regimens. However, broad-spectrum antibiotics for HS are associated with high levels of antibiotic resistance,” she wrote. Prolonged use of ertapenem and other carbapenems in HS treatment “will likely increase antimicrobial resistance, thereby limiting management of both HS and comorbid infections.”

Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, who was asked to comment on the study, said that, despite significant advances in the management of HS over the past decade, there are still patients who do not respond adequately to standard treatments.

For these patients, IV ertapenem can serve as a valuable bridge to a longer-term therapeutic option, “be it surgery or escalated immunomodulation,” such as dual biologic therapy, she said. “In my personal experience, IV ertapenem, which like the authors I also typically use for a 12-week course, delivers impressive and fast results even in the worst disease cases.

“It can be difficult to maintain the therapeutic benefit of ertapenem after it is discontinued, which is why patients should be on concomitant medications as they were in this study and have a post-ertapenem treatment plan in place,” said Dr. Hsiao, who was not involved with the study. “Hopefully, we will be able to one day understand why ertapenem is so effective for HS and be able to harness that benefit for patients without concern for antimicrobial resistance.”

Dr. Cohen reported receiving personal fees from Verrica Pharmaceuticals and belonging to the Board of Trustees of the American Skin Association outside the submitted work. No other disclosures were reported. Dr. Naik reported having received grants from AbbVie and the National Institutes of Health; personal fees from Novartis, UCB, Boehringer Ingelheim, 23andMe, Aristea Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, and Pfizer; and shares from Radera during the conduct of the study. She is a board member of the Hidradenitis Suppurativa Foundation. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, UCB, as a speaker for AbbVie, Novartis, and UCB, and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

To the Editor:

Reported adverse effects following the recombinant zoster vaccine (RZV) include pyrexia, myalgia, and fatigue.¹ We report the case of a patient who developed herpes zoster and subsequent varicella encephalitis within 8 days of receiving the second dose of the RZV.

A 75-year-old man presented to the emergency department with burning pain and pruritus involving the left hip and calf 2 days after receiving the second dose of the RZV. He had a history of chronic lymphocytic leukemia (CLL) and was being clinically monitored. He received the first dose of the RZV without complication 3 months prior. In the emergency department, he was diagnosed with “nerve pain,” given acetaminophen, and discharged home; however, he continued to have worsening pain 8 days later followed by a vesicular eruption that wrapped around the left leg and was concentrated on the inner thigh/groin area in a dermatomal distribution. His primary care physician diagnosed him with herpes zoster and prescribed valacyclovir 1000 mg every 8 hours for 7 days. Two days later, the patient developed weakness and confusion and returned to the emergency department. Upon admission, computed tomography and magnetic resonance imaging/magnetic resonance angiography of the brain was normal. A lumbar puncture confirmed varicella encephalitis via a polymerase chain reaction assay. He was treated with intravenous acyclovir and discharged to a rehabilitation facility. His course was further complicated by a subarachnoid hemorrhage and normal pressure hydrocephalus. He did not require a shunt but continues to have memory impairment, weakness, and cognitive impairment. He is steadily improving with rehabilitative services.

The RZV is an inactivated vaccine composed of the varicella-zoster virus (VZV) glycoprotein E antigen and an adjuvant, AS01_B, that boosts both innate and adaptive immunity.² It was approved by the US Food and Drug Administration in 2017 for prevention of herpes zoster in adults aged 50 years or older. It requires 2 separate injections administered 2 to 6 months apart. Its efficacy for the prevention of cutaneous herpes zoster and postherpetic neuralgia is 97% and 80% to 91%, respectively. It was developed to improve on the existing zoster vaccine live, which contains a live attenuated virus, with efficacy ranging from 38% to 70%.³

The Centers for Disease Control and Prevention initially recommended the RZV for immunocompetent individuals or those taking low-dose immunosuppressant medications as well those who have recovered from an immunocompromising illness. In immunocompetent patients, reported adverse effects include injection site pain and redness, headache, myalgia, fatigue, shivering, fever, and gastrointestinal tract symptoms; however, when the vaccine first came out, many of the studies excluded patients with CLL.⁴ Our patient’s herpes zoster and varicella encephalitis occurred following administration of the second dose of the RZV. Herpes zoster occurs from declining VZV-specific cell-mediated immunity. Given that the vaccine contains inactive virus, it is unlikely that our patient’s infection was the direct result of dissemination of the virus contained within the vaccine. The RZV specifically generates T-cell responses to the glycoprotein E subunit of VZV, which is thought to be responsible for the high levels of VZV-specific memory T cells with the RZV compared to the zoster vaccine live.⁵ However, this response does not occur until after the second dose of RZV. Although our patient already had 1 dose of RZV, it was unlikely that he had a substantial number of glycoprotein E and VZV-specific memory T cells to combat virus reactivation. Additionally, his CLL, though mild, may have resulted in an aberrant T-cell response in the presence of already low VZV-specific lymphocytes, allowing for reactivation and dissemination of the virus. Since then, there has been more of an emphasis on looking at the immunogenicity elicited by the vaccine in patients with CLL­—both those who are treatment naive and those treated with Bruton tyrosine kinase inhibitors. Both groups of patients have demonstrated reduced immunogenicity in response to RZV, leaving the opportunity for viral reactivation in this patient population.^6,7

The safety of the RZV has now been demonstrated in patients with CLL.⁷ However, even after RZV vaccination, patients with CLL are still at risk for herpes zoster reactivation and may have an aberrant response due to immune cell dysregulation. Our case demonstrates the need to increase monitoring of CLL patients for signs of viral reactivation and shift our focus to providing antiviral therapy quickly after symptom occurrence.

To the Editor:

Reported adverse effects following the recombinant zoster vaccine (RZV) include pyrexia, myalgia, and fatigue.¹ We report the case of a patient who developed herpes zoster and subsequent varicella encephalitis within 8 days of receiving the second dose of the RZV.

A 75-year-old man presented to the emergency department with burning pain and pruritus involving the left hip and calf 2 days after receiving the second dose of the RZV. He had a history of chronic lymphocytic leukemia (CLL) and was being clinically monitored. He received the first dose of the RZV without complication 3 months prior. In the emergency department, he was diagnosed with “nerve pain,” given acetaminophen, and discharged home; however, he continued to have worsening pain 8 days later followed by a vesicular eruption that wrapped around the left leg and was concentrated on the inner thigh/groin area in a dermatomal distribution. His primary care physician diagnosed him with herpes zoster and prescribed valacyclovir 1000 mg every 8 hours for 7 days. Two days later, the patient developed weakness and confusion and returned to the emergency department. Upon admission, computed tomography and magnetic resonance imaging/magnetic resonance angiography of the brain was normal. A lumbar puncture confirmed varicella encephalitis via a polymerase chain reaction assay. He was treated with intravenous acyclovir and discharged to a rehabilitation facility. His course was further complicated by a subarachnoid hemorrhage and normal pressure hydrocephalus. He did not require a shunt but continues to have memory impairment, weakness, and cognitive impairment. He is steadily improving with rehabilitative services.

The RZV is an inactivated vaccine composed of the varicella-zoster virus (VZV) glycoprotein E antigen and an adjuvant, AS01_B, that boosts both innate and adaptive immunity.² It was approved by the US Food and Drug Administration in 2017 for prevention of herpes zoster in adults aged 50 years or older. It requires 2 separate injections administered 2 to 6 months apart. Its efficacy for the prevention of cutaneous herpes zoster and postherpetic neuralgia is 97% and 80% to 91%, respectively. It was developed to improve on the existing zoster vaccine live, which contains a live attenuated virus, with efficacy ranging from 38% to 70%.³

The Centers for Disease Control and Prevention initially recommended the RZV for immunocompetent individuals or those taking low-dose immunosuppressant medications as well those who have recovered from an immunocompromising illness. In immunocompetent patients, reported adverse effects include injection site pain and redness, headache, myalgia, fatigue, shivering, fever, and gastrointestinal tract symptoms; however, when the vaccine first came out, many of the studies excluded patients with CLL.⁴ Our patient’s herpes zoster and varicella encephalitis occurred following administration of the second dose of the RZV. Herpes zoster occurs from declining VZV-specific cell-mediated immunity. Given that the vaccine contains inactive virus, it is unlikely that our patient’s infection was the direct result of dissemination of the virus contained within the vaccine. The RZV specifically generates T-cell responses to the glycoprotein E subunit of VZV, which is thought to be responsible for the high levels of VZV-specific memory T cells with the RZV compared to the zoster vaccine live.⁵ However, this response does not occur until after the second dose of RZV. Although our patient already had 1 dose of RZV, it was unlikely that he had a substantial number of glycoprotein E and VZV-specific memory T cells to combat virus reactivation. Additionally, his CLL, though mild, may have resulted in an aberrant T-cell response in the presence of already low VZV-specific lymphocytes, allowing for reactivation and dissemination of the virus. Since then, there has been more of an emphasis on looking at the immunogenicity elicited by the vaccine in patients with CLL­—both those who are treatment naive and those treated with Bruton tyrosine kinase inhibitors. Both groups of patients have demonstrated reduced immunogenicity in response to RZV, leaving the opportunity for viral reactivation in this patient population.^6,7

The safety of the RZV has now been demonstrated in patients with CLL.⁷ However, even after RZV vaccination, patients with CLL are still at risk for herpes zoster reactivation and may have an aberrant response due to immune cell dysregulation. Our case demonstrates the need to increase monitoring of CLL patients for signs of viral reactivation and shift our focus to providing antiviral therapy quickly after symptom occurrence.

To the Editor:

Reported adverse effects following the recombinant zoster vaccine (RZV) include pyrexia, myalgia, and fatigue.¹ We report the case of a patient who developed herpes zoster and subsequent varicella encephalitis within 8 days of receiving the second dose of the RZV.

A 75-year-old man presented to the emergency department with burning pain and pruritus involving the left hip and calf 2 days after receiving the second dose of the RZV. He had a history of chronic lymphocytic leukemia (CLL) and was being clinically monitored. He received the first dose of the RZV without complication 3 months prior. In the emergency department, he was diagnosed with “nerve pain,” given acetaminophen, and discharged home; however, he continued to have worsening pain 8 days later followed by a vesicular eruption that wrapped around the left leg and was concentrated on the inner thigh/groin area in a dermatomal distribution. His primary care physician diagnosed him with herpes zoster and prescribed valacyclovir 1000 mg every 8 hours for 7 days. Two days later, the patient developed weakness and confusion and returned to the emergency department. Upon admission, computed tomography and magnetic resonance imaging/magnetic resonance angiography of the brain was normal. A lumbar puncture confirmed varicella encephalitis via a polymerase chain reaction assay. He was treated with intravenous acyclovir and discharged to a rehabilitation facility. His course was further complicated by a subarachnoid hemorrhage and normal pressure hydrocephalus. He did not require a shunt but continues to have memory impairment, weakness, and cognitive impairment. He is steadily improving with rehabilitative services.

The RZV is an inactivated vaccine composed of the varicella-zoster virus (VZV) glycoprotein E antigen and an adjuvant, AS01_B, that boosts both innate and adaptive immunity.² It was approved by the US Food and Drug Administration in 2017 for prevention of herpes zoster in adults aged 50 years or older. It requires 2 separate injections administered 2 to 6 months apart. Its efficacy for the prevention of cutaneous herpes zoster and postherpetic neuralgia is 97% and 80% to 91%, respectively. It was developed to improve on the existing zoster vaccine live, which contains a live attenuated virus, with efficacy ranging from 38% to 70%.³

The Centers for Disease Control and Prevention initially recommended the RZV for immunocompetent individuals or those taking low-dose immunosuppressant medications as well those who have recovered from an immunocompromising illness. In immunocompetent patients, reported adverse effects include injection site pain and redness, headache, myalgia, fatigue, shivering, fever, and gastrointestinal tract symptoms; however, when the vaccine first came out, many of the studies excluded patients with CLL.⁴ Our patient’s herpes zoster and varicella encephalitis occurred following administration of the second dose of the RZV. Herpes zoster occurs from declining VZV-specific cell-mediated immunity. Given that the vaccine contains inactive virus, it is unlikely that our patient’s infection was the direct result of dissemination of the virus contained within the vaccine. The RZV specifically generates T-cell responses to the glycoprotein E subunit of VZV, which is thought to be responsible for the high levels of VZV-specific memory T cells with the RZV compared to the zoster vaccine live.⁵ However, this response does not occur until after the second dose of RZV. Although our patient already had 1 dose of RZV, it was unlikely that he had a substantial number of glycoprotein E and VZV-specific memory T cells to combat virus reactivation. Additionally, his CLL, though mild, may have resulted in an aberrant T-cell response in the presence of already low VZV-specific lymphocytes, allowing for reactivation and dissemination of the virus. Since then, there has been more of an emphasis on looking at the immunogenicity elicited by the vaccine in patients with CLL­—both those who are treatment naive and those treated with Bruton tyrosine kinase inhibitors. Both groups of patients have demonstrated reduced immunogenicity in response to RZV, leaving the opportunity for viral reactivation in this patient population.^6,7

The safety of the RZV has now been demonstrated in patients with CLL.⁷ However, even after RZV vaccination, patients with CLL are still at risk for herpes zoster reactivation and may have an aberrant response due to immune cell dysregulation. Our case demonstrates the need to increase monitoring of CLL patients for signs of viral reactivation and shift our focus to providing antiviral therapy quickly after symptom occurrence.

To the Editor:

Necrotizing myositis (NM) is an exceedingly rare necrotizing soft-tissue infection (NSTI) that is characterized by skeletal muscle involvement. β -Hemolytic streptococci, such as Streptococcus pyogenes , are the most common causative organisms. The overall prevalence and incidence of NM is unknown. A review of the literature by Adams et al ² identified only 21 cases between 1900 and 1985.

Timely treatment of this infection leads to improved outcomes, but diagnosis can be challenging due to the ambiguous presentation of NM and lack of specific cutaneous changes.³ Clinical manifestations including bullae, blisters, vesicles, and petechiae become more prominent as infection progresses.⁴ If NM is suspected due to cutaneous manifestations, it is imperative that the underlying cause be identified; for example, NM must be distinguished from the overlapping presentation of pyoderma gangrenosum (PG). Because NM has nearly 100% mortality without prompt surgical intervention, early identification is critical.⁵ Herein, we report a case of NM that illustrates the correlation of clinical, histological, and imaging findings required to diagnose this potentially fatal infection.

An 80-year-old man presented to the emergency department with worsening pain, edema, and spreading redness of the right wrist over the last 5 weeks. He had a history of atopic dermatitis that was refractory to topical steroids and methotrexate; he was dependent on an oral steroid (prednisone 30 mg/d) for symptom control. The patient reported minor trauma to the area after performing home renovations. He received numerous rounds of oral antibiotics as an outpatient for presumed cellulitis and reported he was “getting better” but that the signs and symptoms of the condition grew worse after outpatient arthrocentesis. Dermatology was consulted to evaluate for a necrotizing neutrophilic dermatosis such as PG.

At the current presentation, the patient was tachycardic and afebrile (temperature, 98.2 °F [36.8 °C]). Physical examination revealed large, exquisitely tender, ill-defined necrotic ulceration of the right wrist with purulent debris and diffuse edema (Figure 1). Sequential evaluation at 6-hour intervals revealed notably increasing purulence, edema, and tenderness. Interconnected sinus tracts that extended to the fascial plane were observed.

Laboratory workup was notable for a markedly elevated C-reactive protein level of 18.9 mg/dL (reference range, 0–0.8 mg/dL) and an elevated white blood cell count of 19.92×10⁹/L (reference range, 4.5–11.0×10⁹/L). Blood and tissue cultures were positive for methicillin-sensitive Staphylococcus aureus. Computed tomography and magnetic resonance imaging (MRI) prior to biopsy demonstrated findings consistent with extensive subcutaneous and intramuscular areas of loculation and foci of gas (Figure 2). These findings were consistent with intramuscular involvement. A punch biopsy revealed a necrotic epidermis filled with neutrophilic pustules and a dense dermal infiltrate of neutrophilic inflammation consistent with infection (Figure 3).

Emergency surgery was performed with debridement of necrotic tissue and muscle. Postoperatively, he became more clinically stable after being placed on cefazolin through a peripherally inserted central catheter. He underwent 4 additional washouts over the ensuing month, as well as tendon reconstructions, a radial forearm flap, and reverse radial forearm flap reconstruction of the forearm. At the time of publication, there has been no recurrence. The patient’s atopic dermatitis is well controlled on dupilumab and topical fluocinonide alone, with a recent IgA level of 1 g/L and a body surface area measurement of 2%. Dupilumab was started 3 months after surgery.

Necrotizing myositis is a rare, rapidly progressive infection involving muscle that can manifest as superficial cutaneous involvement. The clinical manifestation of NM is harder to recognize than other NSTIs such as necrotizing fasciitis, likely due to the initial prodromal phase of NM, which consists of nonspecific constitutional symptoms.³ Systemic findings such as tachycardia, fever, hypotension, and shock occur in only 10% to 40% of NM patients.^4,5

In our patient, clues of NM included fulfillment of criteria for systemic inflammatory response syndrome at admission and a presumed source of infection; taken together, these findings should lead to a diagnosis of sepsis until otherwise proven. The patient also reported pain that was not proportional to the skin findings, which suggested an NSTI. His lack of constitutional symptoms may have been due to the effects of prednisone, which was changed to dupilumab during hospitalization.

The clinical and histological findings of NM are nonspecific. Clinical findings include skin discoloration with bullae, blisters, vesicles, or petechiae.⁴ Our case adds to the descriptive morphology by including marked edema with ulceration, progressive purulence, and interconnected sinuses tracking to the fascial plane. Histologic findings can include confluent necrosis extending from the epidermis to the underlying muscle with dense neutrophilic inflammation. Notably, these findings can mirror necrotizing neutrophilic dermatoses in the absence of an infectious cause. Failure to recognize simple systemic inflammatory response syndrome criteria in NM patients due to slow treatment response or incorrect treatment can can lead to loss of a limb or death.

Workup reveals overlap with necrotizing neutrophilic dermatoses including PG, which is the prototypical neutrophilic dermatosis. Morphologically, PG presents as an ulcer with a purple and undermined border, often having developed from an initial papule, vesicle, or pustule. A neutrophilic infiltrate of the ulcer edge is the major criterion required to diagnose PG⁶; minor criteria include a positive pathergy test, history of inflammatory arthritis or inflammatory bowel disease, and exclusion of infection.⁶ When compared directly to an NSTI such as NM, the most important variable that sets PG apart is the absence of bacterial growth on blood and tissue cultures.⁷

Imaging studies can aid in the clinical diagnosis of NM and help distinguish the disease from PG. Computed tomography and MRI may demonstrate hallmarks of extensive necrotizing infection, such as gas formation and consequent fascial swelling, thickening and edema of involved muscle, and subfascial fluid collection.^3,4 Distinct from NM, imaging findings in PG are more subtle, suggesting cellulitic inflammation with edema.⁸ A defining radiographic feature of NM can be foci of gas within muscle or fascia, though absence of this finding does not exclude NM.^1,4

In conclusion, NM is a rare intramuscular infection that can be difficult to diagnose due to its nonspecific presentation and lack of constitutional symptoms. Dermatologists should maintain a high level of suspicion for NM in the setting of rapidly progressive clinical findings; accurate diagnosis requires a multimodal approach with complete correlation of clinical, histological, and imaging findings. Computed tomography and MRI can heighten the approach, even when necrotizing neutrophilic dermatoses and NM have similar clinical and histological appearances. Once a diagnosis of NM is established, prompt surgical and medical intervention improves the prognosis.

To the Editor:

Necrotizing myositis (NM) is an exceedingly rare necrotizing soft-tissue infection (NSTI) that is characterized by skeletal muscle involvement. β -Hemolytic streptococci, such as Streptococcus pyogenes , are the most common causative organisms. The overall prevalence and incidence of NM is unknown. A review of the literature by Adams et al ² identified only 21 cases between 1900 and 1985.

Timely treatment of this infection leads to improved outcomes, but diagnosis can be challenging due to the ambiguous presentation of NM and lack of specific cutaneous changes.³ Clinical manifestations including bullae, blisters, vesicles, and petechiae become more prominent as infection progresses.⁴ If NM is suspected due to cutaneous manifestations, it is imperative that the underlying cause be identified; for example, NM must be distinguished from the overlapping presentation of pyoderma gangrenosum (PG). Because NM has nearly 100% mortality without prompt surgical intervention, early identification is critical.⁵ Herein, we report a case of NM that illustrates the correlation of clinical, histological, and imaging findings required to diagnose this potentially fatal infection.

An 80-year-old man presented to the emergency department with worsening pain, edema, and spreading redness of the right wrist over the last 5 weeks. He had a history of atopic dermatitis that was refractory to topical steroids and methotrexate; he was dependent on an oral steroid (prednisone 30 mg/d) for symptom control. The patient reported minor trauma to the area after performing home renovations. He received numerous rounds of oral antibiotics as an outpatient for presumed cellulitis and reported he was “getting better” but that the signs and symptoms of the condition grew worse after outpatient arthrocentesis. Dermatology was consulted to evaluate for a necrotizing neutrophilic dermatosis such as PG.

At the current presentation, the patient was tachycardic and afebrile (temperature, 98.2 °F [36.8 °C]). Physical examination revealed large, exquisitely tender, ill-defined necrotic ulceration of the right wrist with purulent debris and diffuse edema (Figure 1). Sequential evaluation at 6-hour intervals revealed notably increasing purulence, edema, and tenderness. Interconnected sinus tracts that extended to the fascial plane were observed.

Laboratory workup was notable for a markedly elevated C-reactive protein level of 18.9 mg/dL (reference range, 0–0.8 mg/dL) and an elevated white blood cell count of 19.92×10⁹/L (reference range, 4.5–11.0×10⁹/L). Blood and tissue cultures were positive for methicillin-sensitive Staphylococcus aureus. Computed tomography and magnetic resonance imaging (MRI) prior to biopsy demonstrated findings consistent with extensive subcutaneous and intramuscular areas of loculation and foci of gas (Figure 2). These findings were consistent with intramuscular involvement. A punch biopsy revealed a necrotic epidermis filled with neutrophilic pustules and a dense dermal infiltrate of neutrophilic inflammation consistent with infection (Figure 3).

Emergency surgery was performed with debridement of necrotic tissue and muscle. Postoperatively, he became more clinically stable after being placed on cefazolin through a peripherally inserted central catheter. He underwent 4 additional washouts over the ensuing month, as well as tendon reconstructions, a radial forearm flap, and reverse radial forearm flap reconstruction of the forearm. At the time of publication, there has been no recurrence. The patient’s atopic dermatitis is well controlled on dupilumab and topical fluocinonide alone, with a recent IgA level of 1 g/L and a body surface area measurement of 2%. Dupilumab was started 3 months after surgery.

Necrotizing myositis is a rare, rapidly progressive infection involving muscle that can manifest as superficial cutaneous involvement. The clinical manifestation of NM is harder to recognize than other NSTIs such as necrotizing fasciitis, likely due to the initial prodromal phase of NM, which consists of nonspecific constitutional symptoms.³ Systemic findings such as tachycardia, fever, hypotension, and shock occur in only 10% to 40% of NM patients.^4,5

In our patient, clues of NM included fulfillment of criteria for systemic inflammatory response syndrome at admission and a presumed source of infection; taken together, these findings should lead to a diagnosis of sepsis until otherwise proven. The patient also reported pain that was not proportional to the skin findings, which suggested an NSTI. His lack of constitutional symptoms may have been due to the effects of prednisone, which was changed to dupilumab during hospitalization.

The clinical and histological findings of NM are nonspecific. Clinical findings include skin discoloration with bullae, blisters, vesicles, or petechiae.⁴ Our case adds to the descriptive morphology by including marked edema with ulceration, progressive purulence, and interconnected sinuses tracking to the fascial plane. Histologic findings can include confluent necrosis extending from the epidermis to the underlying muscle with dense neutrophilic inflammation. Notably, these findings can mirror necrotizing neutrophilic dermatoses in the absence of an infectious cause. Failure to recognize simple systemic inflammatory response syndrome criteria in NM patients due to slow treatment response or incorrect treatment can can lead to loss of a limb or death.

Workup reveals overlap with necrotizing neutrophilic dermatoses including PG, which is the prototypical neutrophilic dermatosis. Morphologically, PG presents as an ulcer with a purple and undermined border, often having developed from an initial papule, vesicle, or pustule. A neutrophilic infiltrate of the ulcer edge is the major criterion required to diagnose PG⁶; minor criteria include a positive pathergy test, history of inflammatory arthritis or inflammatory bowel disease, and exclusion of infection.⁶ When compared directly to an NSTI such as NM, the most important variable that sets PG apart is the absence of bacterial growth on blood and tissue cultures.⁷

Imaging studies can aid in the clinical diagnosis of NM and help distinguish the disease from PG. Computed tomography and MRI may demonstrate hallmarks of extensive necrotizing infection, such as gas formation and consequent fascial swelling, thickening and edema of involved muscle, and subfascial fluid collection.^3,4 Distinct from NM, imaging findings in PG are more subtle, suggesting cellulitic inflammation with edema.⁸ A defining radiographic feature of NM can be foci of gas within muscle or fascia, though absence of this finding does not exclude NM.^1,4

In conclusion, NM is a rare intramuscular infection that can be difficult to diagnose due to its nonspecific presentation and lack of constitutional symptoms. Dermatologists should maintain a high level of suspicion for NM in the setting of rapidly progressive clinical findings; accurate diagnosis requires a multimodal approach with complete correlation of clinical, histological, and imaging findings. Computed tomography and MRI can heighten the approach, even when necrotizing neutrophilic dermatoses and NM have similar clinical and histological appearances. Once a diagnosis of NM is established, prompt surgical and medical intervention improves the prognosis.

To the Editor:

Necrotizing myositis (NM) is an exceedingly rare necrotizing soft-tissue infection (NSTI) that is characterized by skeletal muscle involvement. β -Hemolytic streptococci, such as Streptococcus pyogenes , are the most common causative organisms. The overall prevalence and incidence of NM is unknown. A review of the literature by Adams et al ² identified only 21 cases between 1900 and 1985.

Timely treatment of this infection leads to improved outcomes, but diagnosis can be challenging due to the ambiguous presentation of NM and lack of specific cutaneous changes.³ Clinical manifestations including bullae, blisters, vesicles, and petechiae become more prominent as infection progresses.⁴ If NM is suspected due to cutaneous manifestations, it is imperative that the underlying cause be identified; for example, NM must be distinguished from the overlapping presentation of pyoderma gangrenosum (PG). Because NM has nearly 100% mortality without prompt surgical intervention, early identification is critical.⁵ Herein, we report a case of NM that illustrates the correlation of clinical, histological, and imaging findings required to diagnose this potentially fatal infection.

An 80-year-old man presented to the emergency department with worsening pain, edema, and spreading redness of the right wrist over the last 5 weeks. He had a history of atopic dermatitis that was refractory to topical steroids and methotrexate; he was dependent on an oral steroid (prednisone 30 mg/d) for symptom control. The patient reported minor trauma to the area after performing home renovations. He received numerous rounds of oral antibiotics as an outpatient for presumed cellulitis and reported he was “getting better” but that the signs and symptoms of the condition grew worse after outpatient arthrocentesis. Dermatology was consulted to evaluate for a necrotizing neutrophilic dermatosis such as PG.

At the current presentation, the patient was tachycardic and afebrile (temperature, 98.2 °F [36.8 °C]). Physical examination revealed large, exquisitely tender, ill-defined necrotic ulceration of the right wrist with purulent debris and diffuse edema (Figure 1). Sequential evaluation at 6-hour intervals revealed notably increasing purulence, edema, and tenderness. Interconnected sinus tracts that extended to the fascial plane were observed.

Laboratory workup was notable for a markedly elevated C-reactive protein level of 18.9 mg/dL (reference range, 0–0.8 mg/dL) and an elevated white blood cell count of 19.92×10⁹/L (reference range, 4.5–11.0×10⁹/L). Blood and tissue cultures were positive for methicillin-sensitive Staphylococcus aureus. Computed tomography and magnetic resonance imaging (MRI) prior to biopsy demonstrated findings consistent with extensive subcutaneous and intramuscular areas of loculation and foci of gas (Figure 2). These findings were consistent with intramuscular involvement. A punch biopsy revealed a necrotic epidermis filled with neutrophilic pustules and a dense dermal infiltrate of neutrophilic inflammation consistent with infection (Figure 3).

Emergency surgery was performed with debridement of necrotic tissue and muscle. Postoperatively, he became more clinically stable after being placed on cefazolin through a peripherally inserted central catheter. He underwent 4 additional washouts over the ensuing month, as well as tendon reconstructions, a radial forearm flap, and reverse radial forearm flap reconstruction of the forearm. At the time of publication, there has been no recurrence. The patient’s atopic dermatitis is well controlled on dupilumab and topical fluocinonide alone, with a recent IgA level of 1 g/L and a body surface area measurement of 2%. Dupilumab was started 3 months after surgery.

Necrotizing myositis is a rare, rapidly progressive infection involving muscle that can manifest as superficial cutaneous involvement. The clinical manifestation of NM is harder to recognize than other NSTIs such as necrotizing fasciitis, likely due to the initial prodromal phase of NM, which consists of nonspecific constitutional symptoms.³ Systemic findings such as tachycardia, fever, hypotension, and shock occur in only 10% to 40% of NM patients.^4,5

In our patient, clues of NM included fulfillment of criteria for systemic inflammatory response syndrome at admission and a presumed source of infection; taken together, these findings should lead to a diagnosis of sepsis until otherwise proven. The patient also reported pain that was not proportional to the skin findings, which suggested an NSTI. His lack of constitutional symptoms may have been due to the effects of prednisone, which was changed to dupilumab during hospitalization.

The clinical and histological findings of NM are nonspecific. Clinical findings include skin discoloration with bullae, blisters, vesicles, or petechiae.⁴ Our case adds to the descriptive morphology by including marked edema with ulceration, progressive purulence, and interconnected sinuses tracking to the fascial plane. Histologic findings can include confluent necrosis extending from the epidermis to the underlying muscle with dense neutrophilic inflammation. Notably, these findings can mirror necrotizing neutrophilic dermatoses in the absence of an infectious cause. Failure to recognize simple systemic inflammatory response syndrome criteria in NM patients due to slow treatment response or incorrect treatment can can lead to loss of a limb or death.

Workup reveals overlap with necrotizing neutrophilic dermatoses including PG, which is the prototypical neutrophilic dermatosis. Morphologically, PG presents as an ulcer with a purple and undermined border, often having developed from an initial papule, vesicle, or pustule. A neutrophilic infiltrate of the ulcer edge is the major criterion required to diagnose PG⁶; minor criteria include a positive pathergy test, history of inflammatory arthritis or inflammatory bowel disease, and exclusion of infection.⁶ When compared directly to an NSTI such as NM, the most important variable that sets PG apart is the absence of bacterial growth on blood and tissue cultures.⁷

Imaging studies can aid in the clinical diagnosis of NM and help distinguish the disease from PG. Computed tomography and MRI may demonstrate hallmarks of extensive necrotizing infection, such as gas formation and consequent fascial swelling, thickening and edema of involved muscle, and subfascial fluid collection.^3,4 Distinct from NM, imaging findings in PG are more subtle, suggesting cellulitic inflammation with edema.⁸ A defining radiographic feature of NM can be foci of gas within muscle or fascia, though absence of this finding does not exclude NM.^1,4

In conclusion, NM is a rare intramuscular infection that can be difficult to diagnose due to its nonspecific presentation and lack of constitutional symptoms. Dermatologists should maintain a high level of suspicion for NM in the setting of rapidly progressive clinical findings; accurate diagnosis requires a multimodal approach with complete correlation of clinical, histological, and imaging findings. Computed tomography and MRI can heighten the approach, even when necrotizing neutrophilic dermatoses and NM have similar clinical and histological appearances. Once a diagnosis of NM is established, prompt surgical and medical intervention improves the prognosis.

Cutaneous reactions associated with the Pfizer-BioNTech COVID-19 vaccine have been reported worldwide since December 2020. Local injection site reactions (<1%) such as erythema, swelling, delayed local reactions (1%–10%), morbilliform rash, urticarial reactions, pityriasis rosea, Rowell syndrome, and lichen planus have been reported following the Pfizer-BioNTech COVID-19 vaccine.¹ Cutaneous reactions reported in association with the Sinovac-Coronavac COVID-19 vaccine include swelling, redness, itching, discoloration, induration (1%–10%), urticaria, petechial rash, and exacerbation of psoriasis at the local injection site (<1%).²

We describe 7 patients from Turkey who presented with various dermatologic problems 5 to 28 days after COVID-19 vaccination, highlighting the possibility of early and late cutaneous reactions related to the vaccine (Table).

Case Reports

Patient 1—A 44-year-old woman was admitted to the dermatology clinic with painful lesions on the trunk of 3 days’ duration. Dermatologic examination revealed grouped erythematous vesicles showing dermatomal spread in the right thoracolumbar (dermatome T10) region. The patient reported that she had received 2 doses of the Sinovac-Coronavac vaccine (doses 1 and 2) and 2 doses of the BioNTech COVID-19 vaccine (doses 3 and 4); the rash had developed 28 days after she received the 4th dose. Her medical history was unremarkable. The lesions regressed after 1 week of treatment with oral valacyclovir 1000 mg 3 times daily, but she developed postherpetic neuralgia 1 week after starting treatment, which resolved after 8 weeks.

Patient 2—A 68-year-old woman presented to the dermatology clinic for evaluation of painful sores on the upper lip of 1 day’s duration. She had a history of rheumatoid arthritis, hypertension, and atopy and was currently taking prednisone and etanercept. Dermatologic examination revealed grouped vesicles on an erythematous base on the upper lip. A diagnosis of herpes labialis was made. The patient reported that she had received a third dose of the Sinovac-Coronavac vaccine 10 days prior to the appearance of the lesions. Her symptoms resolved completely within 2 weeks of treatment with topical acyclovir.

Patient 3—A 64-year-old woman was admitted to the hospital with pain, redness, and watery sores on and around the left eyelid of 2 days’ duration. Dermatologic evaluation revealed the erythematous surface of the left eyelid and periorbital area showed partial crusts, clustered vesicles, erythema, and edema. Additionally, the conjunctiva was purulent and erythematous. The patient’s medical history was notable for allergic asthma, hypertension, anxiety, and depression. For this reason, the patient was prescribed an angiotensin receptor blocker and a selective serotonin reuptake inhibitor. She noted that a similar rash had developed around the left eye 6 years prior that was diagnosed as herpes zoster (HZ). She also reported that she had received 2 doses of the Sinovac-Coronavac COVID-19 vaccine followed by 1 dose of the BioNTech COVID-19 vaccine, which she had received 2 weeks before the rash developed. The patient was treated at the eye clinic and was found to have ocular involvement. Ophthalmology was consulted and a diagnosis of herpes zoster ophthalmicus (HZO) was made. Systemic valacyclovir treatment was initiated, resulting in clinical improvement within 3 weeks.

Patient 4—A 75-year-old man was admitted to the hospital with chest and back pain and widespread muscle pain of several days’ duration. His medical history was remarkable for diabetes mellitus, hypertension, depression, and coronary artery bypass surgery. A medication history revealed treatment with a β-blocker, acetylsalicylic acid, a calcium channel blocker, a dipeptidyl peptidase 4 inhibitor, and a selective serotonin reuptake inhibitor. Dermatologic examination revealed grouped vesicles on an erythematous background in dermatome T5 on the right chest and back. A diagnosis of HZ was made. The patient reported that he had received 2 doses of the Sinovac-Coronavac vaccine followed by 1 dose of the Pfizer-BioNTech vaccine 2 weeks prior to the current presentation. He was treated with valacyclovir for 1 week, and his symptoms resolved entirely within 3 weeks.

Patient 5—A 50-year-old woman presented to the hospital for evaluation of painful sores on the back, chest, groin, and abdomen of 10 days’ duration. The lesions initially had developed 7 days after receiving the BioNTech COVID-19 vaccine; she previously had received 2 doses of the Sinovac-Coronavac vaccine. The patient had a history of untreated psoriasis. Dermatologic examination revealed grouped vesicles on an erythematous background in the T2–L2 dermatomes on the left side of the trunk. A diagnosis of HZ was made. The lesions resolved after 1 week of treatment with systemic valacyclovir; however, she subsequently developed postherpetic neuralgia, hypoesthesia, and postinflammatory hyperpigmentation in the affected regions.

Patient 6—A 37-year-old woman presented to the hospital with redness, swelling, and itching all over the body of 3 days’ duration. The patient noted that the rash would subside and reappear throughout the day. Her medical history was unremarkable, except for COVID-19 infection 6 months prior. She had received a second dose of the BioNTech vaccine 20 days prior to development of symptoms. Dermatologic examination revealed widespread erythematous urticarial plaques. A diagnosis of acute urticaria was made. The patient recovered completely after 1 week of treatment with a systemic steroid and 3 weeks of antihistamine treatment.

Patient 7—A 63-year-old woman presented to the hospital with widespread itching and rash that appeared 5 days after the first dose of the BioNTech COVID-19 vaccine. The patient reported that the rash resolved spontaneously within a few hours but then reappeared. Her medical history revealed that she was taking tamoxifen for breast cancer and that she previously had received 2 doses of the Sinovac-Coronavac vaccine. Dermatologic examination revealed erythematous urticarial plaques on the trunk and arms. A diagnosis of urticaria was made, and her symptoms resolved after 6 weeks of antihistamine treatment.

Comment

Skin lesions associated with COVID-19 infection have been reported worldwide^3,4 as well as dermatologic reactions following COVID-19 vaccination. In one case from Turkey, HZ infection was reported in a 68-year-old man 5 days after he received a second dose of the COVID-19 vaccine.⁵ In another case, HZ infection developed in a 78-year-old man 5 days after COVID-19 vaccination.⁶ Numerous cases of HZ infection developing within 1 to 26 days of COVID-19 vaccination have been reported worldwide.^7-9

In a study conducted in the United States, 40 skin reactions associated with the COVID-19 vaccine were investigated; of these cases, 87.5% (35/40) were reported as varicella-zoster virus, and 12.5% (5/40) were reported as herpes simplex reactivation; 54% (19/35) and 80% (4/5) of these cases, respectively, were associated with the Pfizer-BioNTech vaccine.¹⁰ The average age of patients who developed a skin reaction was 46 years, and 70% (28/40) were women. The time to onset of the reaction was 2 to 13 days after vaccination, and symptoms were reported to improve within 7 days on average.¹⁰

Another study from Spain examined 405 vaccine-related skin reactions, 40.2% of which were related to the Pfizer-BioNTech vaccine. Among them, 80.2% occurred in women; 13.8% of cases were diagnosed as varicella-zoster virus or HZ virus reactivation, and 14.6% were urticaria. Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.¹¹ One study reported 414 skin reactions from the COVID-19 vaccine from December 2020 to February 2021; of these cases, 83% occurred after the Moderna vaccine, which is not available in Turkey, and 17% occurred after the Pfizer-BioNTech vaccine.¹²A systematic review of 91 patients who developed HZ infection after COVID-19 vaccination reported that 10% (9/91) of cases were receiving immunosuppressive therapy and 13% (12/91) had an autoimmune disease.⁷ In our case series, it is known that at least 2 of the patients (patients 2 and 5), including 1 patient with rheumatoid arthritis (patient 2) who was on immunosuppressive treatment, had autoimmune disorders. However, reports in the literature indicate that most patients with autoimmune inflammatory rheumatic diseases remain stable after vaccination.¹³

Herpes zoster ophthalmicus is a rare form of HZ caused by involvement of the ophthalmic branch of the trigeminal nerve that manifests as vesicular lesions and retinitis, uveitis, keratitis, conjunctivitis, and pain on an erythematous background. Two cases of women who developed HZO infection after Pfizer-BioNTech vaccination were reported in the literature.¹⁴ Although patient 3 in our case series had a history of HZO 6 years prior, the possibility of the Pfizer-BioNTech vaccine triggering HZO should be taken into consideration.

Although cutaneous reactions after the Sinovac-Coronavac vaccine were observed in only 1 of 7 patients in our case series, skin reactions after Sinovac-Coronavac (an inactivated viral vaccine) have been reported in the literature. In one study, after a total of 35,229 injections, the incidence of cutaneous adverse events due to Sinovac-Coronavac was reported to be 0.94% and 0.70% after the first and second doses, respectively.¹⁵ Therefore, further study results are needed to directly attribute the reactions to COVID-19 vaccination.

Conclusion

Our case series highlights that clinicians should be vigilant in diagnosing cutaneous reactions following COVID-19 vaccination early to prevent potential complications. Early recognition of reactions is crucial, and the prognosis can be improved with appropriate treatment. Despite the potential dermatologic adverse effects of the COVID-19 vaccine, the most effective way to protect against serious COVID-19 infection is to continue to be vaccinated.

Cutaneous reactions associated with the Pfizer-BioNTech COVID-19 vaccine have been reported worldwide since December 2020. Local injection site reactions (<1%) such as erythema, swelling, delayed local reactions (1%–10%), morbilliform rash, urticarial reactions, pityriasis rosea, Rowell syndrome, and lichen planus have been reported following the Pfizer-BioNTech COVID-19 vaccine.¹ Cutaneous reactions reported in association with the Sinovac-Coronavac COVID-19 vaccine include swelling, redness, itching, discoloration, induration (1%–10%), urticaria, petechial rash, and exacerbation of psoriasis at the local injection site (<1%).²

We describe 7 patients from Turkey who presented with various dermatologic problems 5 to 28 days after COVID-19 vaccination, highlighting the possibility of early and late cutaneous reactions related to the vaccine (Table).

Case Reports

Patient 1—A 44-year-old woman was admitted to the dermatology clinic with painful lesions on the trunk of 3 days’ duration. Dermatologic examination revealed grouped erythematous vesicles showing dermatomal spread in the right thoracolumbar (dermatome T10) region. The patient reported that she had received 2 doses of the Sinovac-Coronavac vaccine (doses 1 and 2) and 2 doses of the BioNTech COVID-19 vaccine (doses 3 and 4); the rash had developed 28 days after she received the 4th dose. Her medical history was unremarkable. The lesions regressed after 1 week of treatment with oral valacyclovir 1000 mg 3 times daily, but she developed postherpetic neuralgia 1 week after starting treatment, which resolved after 8 weeks.

Patient 2—A 68-year-old woman presented to the dermatology clinic for evaluation of painful sores on the upper lip of 1 day’s duration. She had a history of rheumatoid arthritis, hypertension, and atopy and was currently taking prednisone and etanercept. Dermatologic examination revealed grouped vesicles on an erythematous base on the upper lip. A diagnosis of herpes labialis was made. The patient reported that she had received a third dose of the Sinovac-Coronavac vaccine 10 days prior to the appearance of the lesions. Her symptoms resolved completely within 2 weeks of treatment with topical acyclovir.

Patient 3—A 64-year-old woman was admitted to the hospital with pain, redness, and watery sores on and around the left eyelid of 2 days’ duration. Dermatologic evaluation revealed the erythematous surface of the left eyelid and periorbital area showed partial crusts, clustered vesicles, erythema, and edema. Additionally, the conjunctiva was purulent and erythematous. The patient’s medical history was notable for allergic asthma, hypertension, anxiety, and depression. For this reason, the patient was prescribed an angiotensin receptor blocker and a selective serotonin reuptake inhibitor. She noted that a similar rash had developed around the left eye 6 years prior that was diagnosed as herpes zoster (HZ). She also reported that she had received 2 doses of the Sinovac-Coronavac COVID-19 vaccine followed by 1 dose of the BioNTech COVID-19 vaccine, which she had received 2 weeks before the rash developed. The patient was treated at the eye clinic and was found to have ocular involvement. Ophthalmology was consulted and a diagnosis of herpes zoster ophthalmicus (HZO) was made. Systemic valacyclovir treatment was initiated, resulting in clinical improvement within 3 weeks.

Patient 4—A 75-year-old man was admitted to the hospital with chest and back pain and widespread muscle pain of several days’ duration. His medical history was remarkable for diabetes mellitus, hypertension, depression, and coronary artery bypass surgery. A medication history revealed treatment with a β-blocker, acetylsalicylic acid, a calcium channel blocker, a dipeptidyl peptidase 4 inhibitor, and a selective serotonin reuptake inhibitor. Dermatologic examination revealed grouped vesicles on an erythematous background in dermatome T5 on the right chest and back. A diagnosis of HZ was made. The patient reported that he had received 2 doses of the Sinovac-Coronavac vaccine followed by 1 dose of the Pfizer-BioNTech vaccine 2 weeks prior to the current presentation. He was treated with valacyclovir for 1 week, and his symptoms resolved entirely within 3 weeks.

Patient 5—A 50-year-old woman presented to the hospital for evaluation of painful sores on the back, chest, groin, and abdomen of 10 days’ duration. The lesions initially had developed 7 days after receiving the BioNTech COVID-19 vaccine; she previously had received 2 doses of the Sinovac-Coronavac vaccine. The patient had a history of untreated psoriasis. Dermatologic examination revealed grouped vesicles on an erythematous background in the T2–L2 dermatomes on the left side of the trunk. A diagnosis of HZ was made. The lesions resolved after 1 week of treatment with systemic valacyclovir; however, she subsequently developed postherpetic neuralgia, hypoesthesia, and postinflammatory hyperpigmentation in the affected regions.

Patient 6—A 37-year-old woman presented to the hospital with redness, swelling, and itching all over the body of 3 days’ duration. The patient noted that the rash would subside and reappear throughout the day. Her medical history was unremarkable, except for COVID-19 infection 6 months prior. She had received a second dose of the BioNTech vaccine 20 days prior to development of symptoms. Dermatologic examination revealed widespread erythematous urticarial plaques. A diagnosis of acute urticaria was made. The patient recovered completely after 1 week of treatment with a systemic steroid and 3 weeks of antihistamine treatment.

Patient 7—A 63-year-old woman presented to the hospital with widespread itching and rash that appeared 5 days after the first dose of the BioNTech COVID-19 vaccine. The patient reported that the rash resolved spontaneously within a few hours but then reappeared. Her medical history revealed that she was taking tamoxifen for breast cancer and that she previously had received 2 doses of the Sinovac-Coronavac vaccine. Dermatologic examination revealed erythematous urticarial plaques on the trunk and arms. A diagnosis of urticaria was made, and her symptoms resolved after 6 weeks of antihistamine treatment.

Comment

Skin lesions associated with COVID-19 infection have been reported worldwide^3,4 as well as dermatologic reactions following COVID-19 vaccination. In one case from Turkey, HZ infection was reported in a 68-year-old man 5 days after he received a second dose of the COVID-19 vaccine.⁵ In another case, HZ infection developed in a 78-year-old man 5 days after COVID-19 vaccination.⁶ Numerous cases of HZ infection developing within 1 to 26 days of COVID-19 vaccination have been reported worldwide.^7-9

In a study conducted in the United States, 40 skin reactions associated with the COVID-19 vaccine were investigated; of these cases, 87.5% (35/40) were reported as varicella-zoster virus, and 12.5% (5/40) were reported as herpes simplex reactivation; 54% (19/35) and 80% (4/5) of these cases, respectively, were associated with the Pfizer-BioNTech vaccine.¹⁰ The average age of patients who developed a skin reaction was 46 years, and 70% (28/40) were women. The time to onset of the reaction was 2 to 13 days after vaccination, and symptoms were reported to improve within 7 days on average.¹⁰

Another study from Spain examined 405 vaccine-related skin reactions, 40.2% of which were related to the Pfizer-BioNTech vaccine. Among them, 80.2% occurred in women; 13.8% of cases were diagnosed as varicella-zoster virus or HZ virus reactivation, and 14.6% were urticaria. Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.¹¹ One study reported 414 skin reactions from the COVID-19 vaccine from December 2020 to February 2021; of these cases, 83% occurred after the Moderna vaccine, which is not available in Turkey, and 17% occurred after the Pfizer-BioNTech vaccine.¹²A systematic review of 91 patients who developed HZ infection after COVID-19 vaccination reported that 10% (9/91) of cases were receiving immunosuppressive therapy and 13% (12/91) had an autoimmune disease.⁷ In our case series, it is known that at least 2 of the patients (patients 2 and 5), including 1 patient with rheumatoid arthritis (patient 2) who was on immunosuppressive treatment, had autoimmune disorders. However, reports in the literature indicate that most patients with autoimmune inflammatory rheumatic diseases remain stable after vaccination.¹³

Herpes zoster ophthalmicus is a rare form of HZ caused by involvement of the ophthalmic branch of the trigeminal nerve that manifests as vesicular lesions and retinitis, uveitis, keratitis, conjunctivitis, and pain on an erythematous background. Two cases of women who developed HZO infection after Pfizer-BioNTech vaccination were reported in the literature.¹⁴ Although patient 3 in our case series had a history of HZO 6 years prior, the possibility of the Pfizer-BioNTech vaccine triggering HZO should be taken into consideration.

Although cutaneous reactions after the Sinovac-Coronavac vaccine were observed in only 1 of 7 patients in our case series, skin reactions after Sinovac-Coronavac (an inactivated viral vaccine) have been reported in the literature. In one study, after a total of 35,229 injections, the incidence of cutaneous adverse events due to Sinovac-Coronavac was reported to be 0.94% and 0.70% after the first and second doses, respectively.¹⁵ Therefore, further study results are needed to directly attribute the reactions to COVID-19 vaccination.

Conclusion

Our case series highlights that clinicians should be vigilant in diagnosing cutaneous reactions following COVID-19 vaccination early to prevent potential complications. Early recognition of reactions is crucial, and the prognosis can be improved with appropriate treatment. Despite the potential dermatologic adverse effects of the COVID-19 vaccine, the most effective way to protect against serious COVID-19 infection is to continue to be vaccinated.

Cutaneous reactions associated with the Pfizer-BioNTech COVID-19 vaccine have been reported worldwide since December 2020. Local injection site reactions (<1%) such as erythema, swelling, delayed local reactions (1%–10%), morbilliform rash, urticarial reactions, pityriasis rosea, Rowell syndrome, and lichen planus have been reported following the Pfizer-BioNTech COVID-19 vaccine.¹ Cutaneous reactions reported in association with the Sinovac-Coronavac COVID-19 vaccine include swelling, redness, itching, discoloration, induration (1%–10%), urticaria, petechial rash, and exacerbation of psoriasis at the local injection site (<1%).²

We describe 7 patients from Turkey who presented with various dermatologic problems 5 to 28 days after COVID-19 vaccination, highlighting the possibility of early and late cutaneous reactions related to the vaccine (Table).

Case Reports

Patient 1—A 44-year-old woman was admitted to the dermatology clinic with painful lesions on the trunk of 3 days’ duration. Dermatologic examination revealed grouped erythematous vesicles showing dermatomal spread in the right thoracolumbar (dermatome T10) region. The patient reported that she had received 2 doses of the Sinovac-Coronavac vaccine (doses 1 and 2) and 2 doses of the BioNTech COVID-19 vaccine (doses 3 and 4); the rash had developed 28 days after she received the 4th dose. Her medical history was unremarkable. The lesions regressed after 1 week of treatment with oral valacyclovir 1000 mg 3 times daily, but she developed postherpetic neuralgia 1 week after starting treatment, which resolved after 8 weeks.

Patient 2—A 68-year-old woman presented to the dermatology clinic for evaluation of painful sores on the upper lip of 1 day’s duration. She had a history of rheumatoid arthritis, hypertension, and atopy and was currently taking prednisone and etanercept. Dermatologic examination revealed grouped vesicles on an erythematous base on the upper lip. A diagnosis of herpes labialis was made. The patient reported that she had received a third dose of the Sinovac-Coronavac vaccine 10 days prior to the appearance of the lesions. Her symptoms resolved completely within 2 weeks of treatment with topical acyclovir.

Patient 3—A 64-year-old woman was admitted to the hospital with pain, redness, and watery sores on and around the left eyelid of 2 days’ duration. Dermatologic evaluation revealed the erythematous surface of the left eyelid and periorbital area showed partial crusts, clustered vesicles, erythema, and edema. Additionally, the conjunctiva was purulent and erythematous. The patient’s medical history was notable for allergic asthma, hypertension, anxiety, and depression. For this reason, the patient was prescribed an angiotensin receptor blocker and a selective serotonin reuptake inhibitor. She noted that a similar rash had developed around the left eye 6 years prior that was diagnosed as herpes zoster (HZ). She also reported that she had received 2 doses of the Sinovac-Coronavac COVID-19 vaccine followed by 1 dose of the BioNTech COVID-19 vaccine, which she had received 2 weeks before the rash developed. The patient was treated at the eye clinic and was found to have ocular involvement. Ophthalmology was consulted and a diagnosis of herpes zoster ophthalmicus (HZO) was made. Systemic valacyclovir treatment was initiated, resulting in clinical improvement within 3 weeks.

Patient 4—A 75-year-old man was admitted to the hospital with chest and back pain and widespread muscle pain of several days’ duration. His medical history was remarkable for diabetes mellitus, hypertension, depression, and coronary artery bypass surgery. A medication history revealed treatment with a β-blocker, acetylsalicylic acid, a calcium channel blocker, a dipeptidyl peptidase 4 inhibitor, and a selective serotonin reuptake inhibitor. Dermatologic examination revealed grouped vesicles on an erythematous background in dermatome T5 on the right chest and back. A diagnosis of HZ was made. The patient reported that he had received 2 doses of the Sinovac-Coronavac vaccine followed by 1 dose of the Pfizer-BioNTech vaccine 2 weeks prior to the current presentation. He was treated with valacyclovir for 1 week, and his symptoms resolved entirely within 3 weeks.

Patient 5—A 50-year-old woman presented to the hospital for evaluation of painful sores on the back, chest, groin, and abdomen of 10 days’ duration. The lesions initially had developed 7 days after receiving the BioNTech COVID-19 vaccine; she previously had received 2 doses of the Sinovac-Coronavac vaccine. The patient had a history of untreated psoriasis. Dermatologic examination revealed grouped vesicles on an erythematous background in the T2–L2 dermatomes on the left side of the trunk. A diagnosis of HZ was made. The lesions resolved after 1 week of treatment with systemic valacyclovir; however, she subsequently developed postherpetic neuralgia, hypoesthesia, and postinflammatory hyperpigmentation in the affected regions.

Patient 6—A 37-year-old woman presented to the hospital with redness, swelling, and itching all over the body of 3 days’ duration. The patient noted that the rash would subside and reappear throughout the day. Her medical history was unremarkable, except for COVID-19 infection 6 months prior. She had received a second dose of the BioNTech vaccine 20 days prior to development of symptoms. Dermatologic examination revealed widespread erythematous urticarial plaques. A diagnosis of acute urticaria was made. The patient recovered completely after 1 week of treatment with a systemic steroid and 3 weeks of antihistamine treatment.

Patient 7—A 63-year-old woman presented to the hospital with widespread itching and rash that appeared 5 days after the first dose of the BioNTech COVID-19 vaccine. The patient reported that the rash resolved spontaneously within a few hours but then reappeared. Her medical history revealed that she was taking tamoxifen for breast cancer and that she previously had received 2 doses of the Sinovac-Coronavac vaccine. Dermatologic examination revealed erythematous urticarial plaques on the trunk and arms. A diagnosis of urticaria was made, and her symptoms resolved after 6 weeks of antihistamine treatment.

Comment

Skin lesions associated with COVID-19 infection have been reported worldwide^3,4 as well as dermatologic reactions following COVID-19 vaccination. In one case from Turkey, HZ infection was reported in a 68-year-old man 5 days after he received a second dose of the COVID-19 vaccine.⁵ In another case, HZ infection developed in a 78-year-old man 5 days after COVID-19 vaccination.⁶ Numerous cases of HZ infection developing within 1 to 26 days of COVID-19 vaccination have been reported worldwide.^7-9

In a study conducted in the United States, 40 skin reactions associated with the COVID-19 vaccine were investigated; of these cases, 87.5% (35/40) were reported as varicella-zoster virus, and 12.5% (5/40) were reported as herpes simplex reactivation; 54% (19/35) and 80% (4/5) of these cases, respectively, were associated with the Pfizer-BioNTech vaccine.¹⁰ The average age of patients who developed a skin reaction was 46 years, and 70% (28/40) were women. The time to onset of the reaction was 2 to 13 days after vaccination, and symptoms were reported to improve within 7 days on average.¹⁰

Another study from Spain examined 405 vaccine-related skin reactions, 40.2% of which were related to the Pfizer-BioNTech vaccine. Among them, 80.2% occurred in women; 13.8% of cases were diagnosed as varicella-zoster virus or HZ virus reactivation, and 14.6% were urticaria. Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.¹¹ One study reported 414 skin reactions from the COVID-19 vaccine from December 2020 to February 2021; of these cases, 83% occurred after the Moderna vaccine, which is not available in Turkey, and 17% occurred after the Pfizer-BioNTech vaccine.¹²A systematic review of 91 patients who developed HZ infection after COVID-19 vaccination reported that 10% (9/91) of cases were receiving immunosuppressive therapy and 13% (12/91) had an autoimmune disease.⁷ In our case series, it is known that at least 2 of the patients (patients 2 and 5), including 1 patient with rheumatoid arthritis (patient 2) who was on immunosuppressive treatment, had autoimmune disorders. However, reports in the literature indicate that most patients with autoimmune inflammatory rheumatic diseases remain stable after vaccination.¹³

Herpes zoster ophthalmicus is a rare form of HZ caused by involvement of the ophthalmic branch of the trigeminal nerve that manifests as vesicular lesions and retinitis, uveitis, keratitis, conjunctivitis, and pain on an erythematous background. Two cases of women who developed HZO infection after Pfizer-BioNTech vaccination were reported in the literature.¹⁴ Although patient 3 in our case series had a history of HZO 6 years prior, the possibility of the Pfizer-BioNTech vaccine triggering HZO should be taken into consideration.

Although cutaneous reactions after the Sinovac-Coronavac vaccine were observed in only 1 of 7 patients in our case series, skin reactions after Sinovac-Coronavac (an inactivated viral vaccine) have been reported in the literature. In one study, after a total of 35,229 injections, the incidence of cutaneous adverse events due to Sinovac-Coronavac was reported to be 0.94% and 0.70% after the first and second doses, respectively.¹⁵ Therefore, further study results are needed to directly attribute the reactions to COVID-19 vaccination.

Conclusion

Our case series highlights that clinicians should be vigilant in diagnosing cutaneous reactions following COVID-19 vaccination early to prevent potential complications. Early recognition of reactions is crucial, and the prognosis can be improved with appropriate treatment. Despite the potential dermatologic adverse effects of the COVID-19 vaccine, the most effective way to protect against serious COVID-19 infection is to continue to be vaccinated.

Dermatologists in training are exposed to many different clinical scenarios—from the quick 15-minute encounter to diagnose a case of atopic dermatitis to hours of digging through a medical record to identify a culprit medication in a hospitalized patient with a life-threatening cutaneous drug reaction. Amidst the day-to-day clinical work that we do, there inevitably are interactions we have with patients that are less than ideal. These challenging encounters—whether they be subtle microaggressions that unfortunately enter the workplace or blatant quarrels between providers and patients that leave both parties dissatisfied—are notable contributors to physician stress levels and can lead to burnout.^1,2 However, there are positive lessons to be learned from these challenging patient encounters if we manage to withstand them. When we start to understand the factors contributing to difficult clinical encounters, we can begin to develop and apply effective communication tools to productively navigate these experiences.

Defining the Difficult Patient

In 2017, the Global Burden of Disease study revealed that skin disease is the fourth leading cause of nonfatal disease burden worldwide.³ Based on this statistic, it is easy to see how some patients may experience frustration associated with their condition and subsequently displace their discontent on the physician. In one study, nearly 1 of every 6 (16.7%) outpatient encounters was considered difficult by physicians.⁴ Family medicine physicians defined the difficult patient as one who is violent, demanding, aggressive, and rude.⁵ Others in primary care specialties have considered difficult patients to have characteristics that include mental health problems, more than 5 somatic symptoms, and abrasive personalities.^4,6

Situational and Physician-Centered Factors in Difficult Patient Encounters

In our medical system, the narrative often is focused on the patient, for better or worse—the patient was difficult, thereby making the encounter difficult. However, it is important to remember that difficult encounters can be attributed to several different factors, including those related to the physician, the clinical situation, or both. For example, dermatology residents juggle their clinical duties; academic work including studying, teaching, and/or research; and systemic and personal pressures at all times, whether they are cognizant of it or not. For better or worse, by virtue of being human, residents bring these factors with them to each clinical encounter. The delicate balance of these components can have a considerable impact on our delivery of good health care. This is particularly relevant in dermatology, where residents are subject to limited time during visits, work culture among clinic staff that is out of our control, and prominent complex social issues (for those of us practicing in medically underserved areas). Poor communication skills, underlying bias toward specific health conditions, limited knowledge as a trainee, and our own personal stressors also may play large roles in perceiving a clinical encounter as difficult during dermatology residency.⁷

Strategies to Mitigate Difficult Encounters

As a resident, if you make a statement that sparks a negative response from the patient, acknowledge their negative emotion, try to offer help, or rephrase the original statement to quickly dispel the tension. Validating a patient’s emotions and helping them embrace uncertainty can go a long way in the therapeutic relationship, especially in dermatology where so many of our diseases are chronic and without a definite cure.⁸ Additionally, it is important to apply strategies to redirect and de-escalate the situation during emotionally charged conversations, such as active listening, validating and empathizing with emotions, exploring alternative solutions, and providing closure to the conversation. Consensus recommendations for managing challenging encounters established by the American Academy of Family Physicians in 2013 include setting boundaries or modifying schedules, as needed, to handle difficult encounters; employing empathetic listening skills and a nonjudgmental attitude to facilitate trust and adherence to treatment; and assessing for underlying psychological illnesses with referral for appropriate diagnosis and treatment. Finally, the CALMER method—catalyst for change, alter thoughts to change feelings, listen and then make a diagnosis, make an agreement, education and follow-up, reach out and discuss feelings—is another approach that may be useful.⁷ In dermatology, this approach may not only dissipate unwanted tension but also make progress toward a therapeutic relationship. We cannot control the patient’s behavior in a visit, but we need to keep in mind that we are in control of our own reactions to said behavior.⁹ After first acknowledging this, we can then guide patients to take steps toward overcoming the issue. Within the time restrictions of a dermatology clinic visit, residents may use this approach to quickly feel more in control of a distressing situation and remain calm to better care for the patient.

Final Thoughts

Difficult patient encounters are impossible to avoid in any field of medicine, and dermatology is no exception. It will only benefit residents to recognize the multiple factors impacting a challenging encounter now and learn or enhance conflict resolution and communication skills to navigate these dissatisfying and uncomfortable situations, as they are inevitable in our careers.

Dermatologists in training are exposed to many different clinical scenarios—from the quick 15-minute encounter to diagnose a case of atopic dermatitis to hours of digging through a medical record to identify a culprit medication in a hospitalized patient with a life-threatening cutaneous drug reaction. Amidst the day-to-day clinical work that we do, there inevitably are interactions we have with patients that are less than ideal. These challenging encounters—whether they be subtle microaggressions that unfortunately enter the workplace or blatant quarrels between providers and patients that leave both parties dissatisfied—are notable contributors to physician stress levels and can lead to burnout.^1,2 However, there are positive lessons to be learned from these challenging patient encounters if we manage to withstand them. When we start to understand the factors contributing to difficult clinical encounters, we can begin to develop and apply effective communication tools to productively navigate these experiences.

Defining the Difficult Patient

In 2017, the Global Burden of Disease study revealed that skin disease is the fourth leading cause of nonfatal disease burden worldwide.³ Based on this statistic, it is easy to see how some patients may experience frustration associated with their condition and subsequently displace their discontent on the physician. In one study, nearly 1 of every 6 (16.7%) outpatient encounters was considered difficult by physicians.⁴ Family medicine physicians defined the difficult patient as one who is violent, demanding, aggressive, and rude.⁵ Others in primary care specialties have considered difficult patients to have characteristics that include mental health problems, more than 5 somatic symptoms, and abrasive personalities.^4,6

Situational and Physician-Centered Factors in Difficult Patient Encounters

In our medical system, the narrative often is focused on the patient, for better or worse—the patient was difficult, thereby making the encounter difficult. However, it is important to remember that difficult encounters can be attributed to several different factors, including those related to the physician, the clinical situation, or both. For example, dermatology residents juggle their clinical duties; academic work including studying, teaching, and/or research; and systemic and personal pressures at all times, whether they are cognizant of it or not. For better or worse, by virtue of being human, residents bring these factors with them to each clinical encounter. The delicate balance of these components can have a considerable impact on our delivery of good health care. This is particularly relevant in dermatology, where residents are subject to limited time during visits, work culture among clinic staff that is out of our control, and prominent complex social issues (for those of us practicing in medically underserved areas). Poor communication skills, underlying bias toward specific health conditions, limited knowledge as a trainee, and our own personal stressors also may play large roles in perceiving a clinical encounter as difficult during dermatology residency.⁷

Strategies to Mitigate Difficult Encounters

As a resident, if you make a statement that sparks a negative response from the patient, acknowledge their negative emotion, try to offer help, or rephrase the original statement to quickly dispel the tension. Validating a patient’s emotions and helping them embrace uncertainty can go a long way in the therapeutic relationship, especially in dermatology where so many of our diseases are chronic and without a definite cure.⁸ Additionally, it is important to apply strategies to redirect and de-escalate the situation during emotionally charged conversations, such as active listening, validating and empathizing with emotions, exploring alternative solutions, and providing closure to the conversation. Consensus recommendations for managing challenging encounters established by the American Academy of Family Physicians in 2013 include setting boundaries or modifying schedules, as needed, to handle difficult encounters; employing empathetic listening skills and a nonjudgmental attitude to facilitate trust and adherence to treatment; and assessing for underlying psychological illnesses with referral for appropriate diagnosis and treatment. Finally, the CALMER method—catalyst for change, alter thoughts to change feelings, listen and then make a diagnosis, make an agreement, education and follow-up, reach out and discuss feelings—is another approach that may be useful.⁷ In dermatology, this approach may not only dissipate unwanted tension but also make progress toward a therapeutic relationship. We cannot control the patient’s behavior in a visit, but we need to keep in mind that we are in control of our own reactions to said behavior.⁹ After first acknowledging this, we can then guide patients to take steps toward overcoming the issue. Within the time restrictions of a dermatology clinic visit, residents may use this approach to quickly feel more in control of a distressing situation and remain calm to better care for the patient.

Final Thoughts

Difficult patient encounters are impossible to avoid in any field of medicine, and dermatology is no exception. It will only benefit residents to recognize the multiple factors impacting a challenging encounter now and learn or enhance conflict resolution and communication skills to navigate these dissatisfying and uncomfortable situations, as they are inevitable in our careers.

Dermatologists in training are exposed to many different clinical scenarios—from the quick 15-minute encounter to diagnose a case of atopic dermatitis to hours of digging through a medical record to identify a culprit medication in a hospitalized patient with a life-threatening cutaneous drug reaction. Amidst the day-to-day clinical work that we do, there inevitably are interactions we have with patients that are less than ideal. These challenging encounters—whether they be subtle microaggressions that unfortunately enter the workplace or blatant quarrels between providers and patients that leave both parties dissatisfied—are notable contributors to physician stress levels and can lead to burnout.^1,2 However, there are positive lessons to be learned from these challenging patient encounters if we manage to withstand them. When we start to understand the factors contributing to difficult clinical encounters, we can begin to develop and apply effective communication tools to productively navigate these experiences.

Defining the Difficult Patient

In 2017, the Global Burden of Disease study revealed that skin disease is the fourth leading cause of nonfatal disease burden worldwide.³ Based on this statistic, it is easy to see how some patients may experience frustration associated with their condition and subsequently displace their discontent on the physician. In one study, nearly 1 of every 6 (16.7%) outpatient encounters was considered difficult by physicians.⁴ Family medicine physicians defined the difficult patient as one who is violent, demanding, aggressive, and rude.⁵ Others in primary care specialties have considered difficult patients to have characteristics that include mental health problems, more than 5 somatic symptoms, and abrasive personalities.^4,6

Situational and Physician-Centered Factors in Difficult Patient Encounters

In our medical system, the narrative often is focused on the patient, for better or worse—the patient was difficult, thereby making the encounter difficult. However, it is important to remember that difficult encounters can be attributed to several different factors, including those related to the physician, the clinical situation, or both. For example, dermatology residents juggle their clinical duties; academic work including studying, teaching, and/or research; and systemic and personal pressures at all times, whether they are cognizant of it or not. For better or worse, by virtue of being human, residents bring these factors with them to each clinical encounter. The delicate balance of these components can have a considerable impact on our delivery of good health care. This is particularly relevant in dermatology, where residents are subject to limited time during visits, work culture among clinic staff that is out of our control, and prominent complex social issues (for those of us practicing in medically underserved areas). Poor communication skills, underlying bias toward specific health conditions, limited knowledge as a trainee, and our own personal stressors also may play large roles in perceiving a clinical encounter as difficult during dermatology residency.⁷

Strategies to Mitigate Difficult Encounters

As a resident, if you make a statement that sparks a negative response from the patient, acknowledge their negative emotion, try to offer help, or rephrase the original statement to quickly dispel the tension. Validating a patient’s emotions and helping them embrace uncertainty can go a long way in the therapeutic relationship, especially in dermatology where so many of our diseases are chronic and without a definite cure.⁸ Additionally, it is important to apply strategies to redirect and de-escalate the situation during emotionally charged conversations, such as active listening, validating and empathizing with emotions, exploring alternative solutions, and providing closure to the conversation. Consensus recommendations for managing challenging encounters established by the American Academy of Family Physicians in 2013 include setting boundaries or modifying schedules, as needed, to handle difficult encounters; employing empathetic listening skills and a nonjudgmental attitude to facilitate trust and adherence to treatment; and assessing for underlying psychological illnesses with referral for appropriate diagnosis and treatment. Finally, the CALMER method—catalyst for change, alter thoughts to change feelings, listen and then make a diagnosis, make an agreement, education and follow-up, reach out and discuss feelings—is another approach that may be useful.⁷ In dermatology, this approach may not only dissipate unwanted tension but also make progress toward a therapeutic relationship. We cannot control the patient’s behavior in a visit, but we need to keep in mind that we are in control of our own reactions to said behavior.⁹ After first acknowledging this, we can then guide patients to take steps toward overcoming the issue. Within the time restrictions of a dermatology clinic visit, residents may use this approach to quickly feel more in control of a distressing situation and remain calm to better care for the patient.

Final Thoughts

Difficult patient encounters are impossible to avoid in any field of medicine, and dermatology is no exception. It will only benefit residents to recognize the multiple factors impacting a challenging encounter now and learn or enhance conflict resolution and communication skills to navigate these dissatisfying and uncomfortable situations, as they are inevitable in our careers.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE:

Skin conditions burden many children with inflammatory bowel disease (IBD), according to the authors of a single-center study.

METHODOLOGY:

• Little is known about the prevalence of IBD-associated skin lesions and their association with IBD severity in children ages 18 and younger.Researchers retrospectively reviewed the medical charts of 425 children and adolescents with  (CD) or ulcerative  (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
• Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
• They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
• Researchers retrospectively reviewed the medical charts of 425 children and adolescents with Crohn’s disease (CD) or ulcerative colitis (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
• Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
• They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.

TAKEAWAY:

• The most common noninfectious dermatologic condition among the 425 children and adolescents was  (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%).
• Angular cheilitis was more common among those with CD than those with UC (7.2% vs 2%, respectively; P = .024) as was keratosis pilaris (6.9% vs 0.7%; P = .003), and perianal skin complications such as skin tags (20.3% vs 4%), fistulas (13.4% vs 2.7%), and abscesses (13.4% vs 2%; P < .001 for all associations).
• Fungal skin infections were more frequently diagnosed in children with UC than those with CD (15.4% vs 8%; P = .017).
• The researchers observed that the severity of IBD correlated with a higher prevalence of perianal fistula (P = .003), perianal region abscess (P = .041), psoriasis (P < .001), and pyoderma gangrenosum (P = .003).

IN PRACTICE:

“Early identification of common dermatologic conditions in children and adolescents with IBD and recognizing their characteristic associations may alter management and improve skin-related outcomes in this patient population,” the authors wrote.

SOURCE:

Corresponding author Megha M. Tollefson, MD, of the Department of Dermatology at Mayo Clinic, Rochester, Minnesota, and colleagues conducted the research, which was published in Pediatric Dermatology.

LIMITATIONS:

The single-center design and the fact that database studies are subject to extraction error. There was no age- and sex-matched cohort to determine whether the prevalence of cutaneous infections, acne, eczema, and other inflammatory disorders was truly increased in IBD.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Skin conditions burden many children with inflammatory bowel disease (IBD), according to the authors of a single-center study.

METHODOLOGY:

• Little is known about the prevalence of IBD-associated skin lesions and their association with IBD severity in children ages 18 and younger.Researchers retrospectively reviewed the medical charts of 425 children and adolescents with  (CD) or ulcerative  (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
• Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
• They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
• Researchers retrospectively reviewed the medical charts of 425 children and adolescents with Crohn’s disease (CD) or ulcerative colitis (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
• Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
• They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.

TAKEAWAY:

• The most common noninfectious dermatologic condition among the 425 children and adolescents was  (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%).
• Angular cheilitis was more common among those with CD than those with UC (7.2% vs 2%, respectively; P = .024) as was keratosis pilaris (6.9% vs 0.7%; P = .003), and perianal skin complications such as skin tags (20.3% vs 4%), fistulas (13.4% vs 2.7%), and abscesses (13.4% vs 2%; P < .001 for all associations).
• Fungal skin infections were more frequently diagnosed in children with UC than those with CD (15.4% vs 8%; P = .017).
• The researchers observed that the severity of IBD correlated with a higher prevalence of perianal fistula (P = .003), perianal region abscess (P = .041), psoriasis (P < .001), and pyoderma gangrenosum (P = .003).

IN PRACTICE:

“Early identification of common dermatologic conditions in children and adolescents with IBD and recognizing their characteristic associations may alter management and improve skin-related outcomes in this patient population,” the authors wrote.

SOURCE:

Corresponding author Megha M. Tollefson, MD, of the Department of Dermatology at Mayo Clinic, Rochester, Minnesota, and colleagues conducted the research, which was published in Pediatric Dermatology.

LIMITATIONS:

The single-center design and the fact that database studies are subject to extraction error. There was no age- and sex-matched cohort to determine whether the prevalence of cutaneous infections, acne, eczema, and other inflammatory disorders was truly increased in IBD.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Skin conditions burden many children with inflammatory bowel disease (IBD), according to the authors of a single-center study.

METHODOLOGY:

• Little is known about the prevalence of IBD-associated skin lesions and their association with IBD severity in children ages 18 and younger.Researchers retrospectively reviewed the medical charts of 425 children and adolescents with  (CD) or ulcerative  (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
• Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
• They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
• Researchers retrospectively reviewed the medical charts of 425 children and adolescents with Crohn’s disease (CD) or ulcerative colitis (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
• Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
• They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.

TAKEAWAY:

• The most common noninfectious dermatologic condition among the 425 children and adolescents was  (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%).
• Angular cheilitis was more common among those with CD than those with UC (7.2% vs 2%, respectively; P = .024) as was keratosis pilaris (6.9% vs 0.7%; P = .003), and perianal skin complications such as skin tags (20.3% vs 4%), fistulas (13.4% vs 2.7%), and abscesses (13.4% vs 2%; P < .001 for all associations).
• Fungal skin infections were more frequently diagnosed in children with UC than those with CD (15.4% vs 8%; P = .017).
• The researchers observed that the severity of IBD correlated with a higher prevalence of perianal fistula (P = .003), perianal region abscess (P = .041), psoriasis (P < .001), and pyoderma gangrenosum (P = .003).

IN PRACTICE:

“Early identification of common dermatologic conditions in children and adolescents with IBD and recognizing their characteristic associations may alter management and improve skin-related outcomes in this patient population,” the authors wrote.

SOURCE:

Corresponding author Megha M. Tollefson, MD, of the Department of Dermatology at Mayo Clinic, Rochester, Minnesota, and colleagues conducted the research, which was published in Pediatric Dermatology.

LIMITATIONS:

The single-center design and the fact that database studies are subject to extraction error. There was no age- and sex-matched cohort to determine whether the prevalence of cutaneous infections, acne, eczema, and other inflammatory disorders was truly increased in IBD.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

On February 14, 2024, Galderma announced that the Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for nemolizumab for the treatment of patients with prurigo nodularis and for adolescents and adults with moderate to severe atopic dermatitis.

A first-in-class investigational monoclonal antibody specifically designed to inhibit interleukin (IL) IL-31 signaling, nemolizumab has also been granted FDA Priority Review for prurigo nodularis, according to a press release from the company. The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab for both prurigo nodularis and atopic dermatitis.

The regulatory developments follow data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in patients with prurigo nodularis (NCT04501679 and NCT04501666). According to the press release, in OLYMPIA 1 and 2, 58% and 56% of patients, respectively, achieved at least a least four-point reduction in itch intensity as measured by the peak-pruritus numerical rating scale (PP-NRS), compared with 17% and 21% in the placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the investigator’s global assessment (IGA) score, compared with 7% and 11% in the placebo groups (P < .0001).

On February 14, 2024, Galderma announced that the Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for nemolizumab for the treatment of patients with prurigo nodularis and for adolescents and adults with moderate to severe atopic dermatitis.

A first-in-class investigational monoclonal antibody specifically designed to inhibit interleukin (IL) IL-31 signaling, nemolizumab has also been granted FDA Priority Review for prurigo nodularis, according to a press release from the company. The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab for both prurigo nodularis and atopic dermatitis.

The regulatory developments follow data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in patients with prurigo nodularis (NCT04501679 and NCT04501666). According to the press release, in OLYMPIA 1 and 2, 58% and 56% of patients, respectively, achieved at least a least four-point reduction in itch intensity as measured by the peak-pruritus numerical rating scale (PP-NRS), compared with 17% and 21% in the placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the investigator’s global assessment (IGA) score, compared with 7% and 11% in the placebo groups (P < .0001).

On February 14, 2024, Galderma announced that the Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for nemolizumab for the treatment of patients with prurigo nodularis and for adolescents and adults with moderate to severe atopic dermatitis.

A first-in-class investigational monoclonal antibody specifically designed to inhibit interleukin (IL) IL-31 signaling, nemolizumab has also been granted FDA Priority Review for prurigo nodularis, according to a press release from the company. The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab for both prurigo nodularis and atopic dermatitis.

The regulatory developments follow data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in patients with prurigo nodularis (NCT04501679 and NCT04501666). According to the press release, in OLYMPIA 1 and 2, 58% and 56% of patients, respectively, achieved at least a least four-point reduction in itch intensity as measured by the peak-pruritus numerical rating scale (PP-NRS), compared with 17% and 21% in the placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the investigator’s global assessment (IGA) score, compared with 7% and 11% in the placebo groups (P < .0001).

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.