MDedge Dermatology

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.

During examination, the patient was observed repetitively cracking his knuckles, making a fist with the right hand, placing the left hand on top, and rubbing the hand, a behavior he routinely did multiple times daily. The observed pattern of finger involvement on the dorsum of the right hand corresponded to areas subjected to significant pressure during the described activity. Consequently, a diagnosis of lichen simplex chronicus (LSC) secondary to mechanical rubbing, along with associated pachydermodactyly on the fingers of the right hand, was established.

Lichen simplex chronicus and pachydermodactyly are both attributed to microtrauma inflicted upon the skin. Lichen simplex chronicus often constitutes a diagnosis of exclusion and is characterized by repetitive trauma-induced keratinocyte proliferation and melanocyte activation, resulting in hyperpigmentation and skin thickening. Although typically observed in women between the fourth and fifth decades of life, LSC is rarely reported in children. In adults, LSC-related rubbing or scratching frequently arises from chronic pruritic dermatitis such as eczema or psoriasis, neurodermatitis from dysesthesia, or habitual movements, as exhibited by this young patient. While generally benign, LSC may become infected. In rare instances, malignant transformation may occur.

The association with pachydermodactyly implicates microtrauma, necessitating careful observation and questioning to elucidate the cause, as demonstrated in this case. Lesions are typically hyperpigmented, though cases of associated hypopigmentation or depigmentation have been documented. Affected areas typically fall within the patient’s hand and finger reach, with lesion improvement over several months achievable through trigger avoidance.
 

Pachydermodactyly, a rare but benign fibromatosis around the proximal interphalangeal joints, is often misdiagnosed as juvenile idiopathic arthritis, potentially leading to unnecessary treatments and patient anxiety. Microtrauma history due to digit manipulation is prevalent among affected individuals, with most also exhibiting neuropsychiatric disorders. Histological examination of pachydermodactyly reveals hypergranulosis and dermal thickening, accompanied by increased fibroblasts and collagen types I, III, and V, differing from the epidermal changes seen in LSC.

The differential diagnosis also included phytophotodermatitis, a phototoxic dermatologic reaction following exposure to ultraviolet light subsequent to contact with furocoumarin-containing plant chemicals. However, the persistence of the patient’s lesions for over a year precluded this diagnosis. Secondary hyperpigmentation was also contemplated but excluded due to the absence of preceding inflammatory dermatitis.

Treatment of LSC primarily involves identifying and addressing any underlying conditions, repairing the skin barrier, reducing inflammation, and modifying behaviors contributing to chronic microtrauma, as observed in this patient. Topical corticosteroids may aid in decreasing epidermal thickening and discoloration, though lesion resolution necessitates behavior cessation.

It’s important to identify these types of skin changes in children to avoid unnecessary medical treatments for these benign conditions.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

Suggested Reading

Seier JA, Dissemond J. Lichen Simplex Chronicus Due to Mechanical Irritation. Dtsch Arztebl Int. 2022 Nov 18;119(46):802. doi: 10.3238/arztebl.m2022.0213.

Small S et al. A 12-Year-Old Boy Presenting With Unilateral Proximal Interphalangeal Joint Swelling. BMJ Case Rep. 2011 Apr 13:2011:bcr0120113719. doi: 10.1136/bcr.01.2011.3719.

Voicu C et al Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade. Open Access Maced J Med Sci. 2017 Jul 24;5(4):556-557. doi: 10.3889/oamjms.2017.133.

During examination, the patient was observed repetitively cracking his knuckles, making a fist with the right hand, placing the left hand on top, and rubbing the hand, a behavior he routinely did multiple times daily. The observed pattern of finger involvement on the dorsum of the right hand corresponded to areas subjected to significant pressure during the described activity. Consequently, a diagnosis of lichen simplex chronicus (LSC) secondary to mechanical rubbing, along with associated pachydermodactyly on the fingers of the right hand, was established.

Lichen simplex chronicus and pachydermodactyly are both attributed to microtrauma inflicted upon the skin. Lichen simplex chronicus often constitutes a diagnosis of exclusion and is characterized by repetitive trauma-induced keratinocyte proliferation and melanocyte activation, resulting in hyperpigmentation and skin thickening. Although typically observed in women between the fourth and fifth decades of life, LSC is rarely reported in children. In adults, LSC-related rubbing or scratching frequently arises from chronic pruritic dermatitis such as eczema or psoriasis, neurodermatitis from dysesthesia, or habitual movements, as exhibited by this young patient. While generally benign, LSC may become infected. In rare instances, malignant transformation may occur.

The association with pachydermodactyly implicates microtrauma, necessitating careful observation and questioning to elucidate the cause, as demonstrated in this case. Lesions are typically hyperpigmented, though cases of associated hypopigmentation or depigmentation have been documented. Affected areas typically fall within the patient’s hand and finger reach, with lesion improvement over several months achievable through trigger avoidance.
 

Pachydermodactyly, a rare but benign fibromatosis around the proximal interphalangeal joints, is often misdiagnosed as juvenile idiopathic arthritis, potentially leading to unnecessary treatments and patient anxiety. Microtrauma history due to digit manipulation is prevalent among affected individuals, with most also exhibiting neuropsychiatric disorders. Histological examination of pachydermodactyly reveals hypergranulosis and dermal thickening, accompanied by increased fibroblasts and collagen types I, III, and V, differing from the epidermal changes seen in LSC.

The differential diagnosis also included phytophotodermatitis, a phototoxic dermatologic reaction following exposure to ultraviolet light subsequent to contact with furocoumarin-containing plant chemicals. However, the persistence of the patient’s lesions for over a year precluded this diagnosis. Secondary hyperpigmentation was also contemplated but excluded due to the absence of preceding inflammatory dermatitis.

Treatment of LSC primarily involves identifying and addressing any underlying conditions, repairing the skin barrier, reducing inflammation, and modifying behaviors contributing to chronic microtrauma, as observed in this patient. Topical corticosteroids may aid in decreasing epidermal thickening and discoloration, though lesion resolution necessitates behavior cessation.

It’s important to identify these types of skin changes in children to avoid unnecessary medical treatments for these benign conditions.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

Suggested Reading

Seier JA, Dissemond J. Lichen Simplex Chronicus Due to Mechanical Irritation. Dtsch Arztebl Int. 2022 Nov 18;119(46):802. doi: 10.3238/arztebl.m2022.0213.

Small S et al. A 12-Year-Old Boy Presenting With Unilateral Proximal Interphalangeal Joint Swelling. BMJ Case Rep. 2011 Apr 13:2011:bcr0120113719. doi: 10.1136/bcr.01.2011.3719.

Voicu C et al Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade. Open Access Maced J Med Sci. 2017 Jul 24;5(4):556-557. doi: 10.3889/oamjms.2017.133.

During examination, the patient was observed repetitively cracking his knuckles, making a fist with the right hand, placing the left hand on top, and rubbing the hand, a behavior he routinely did multiple times daily. The observed pattern of finger involvement on the dorsum of the right hand corresponded to areas subjected to significant pressure during the described activity. Consequently, a diagnosis of lichen simplex chronicus (LSC) secondary to mechanical rubbing, along with associated pachydermodactyly on the fingers of the right hand, was established.

Lichen simplex chronicus and pachydermodactyly are both attributed to microtrauma inflicted upon the skin. Lichen simplex chronicus often constitutes a diagnosis of exclusion and is characterized by repetitive trauma-induced keratinocyte proliferation and melanocyte activation, resulting in hyperpigmentation and skin thickening. Although typically observed in women between the fourth and fifth decades of life, LSC is rarely reported in children. In adults, LSC-related rubbing or scratching frequently arises from chronic pruritic dermatitis such as eczema or psoriasis, neurodermatitis from dysesthesia, or habitual movements, as exhibited by this young patient. While generally benign, LSC may become infected. In rare instances, malignant transformation may occur.

The association with pachydermodactyly implicates microtrauma, necessitating careful observation and questioning to elucidate the cause, as demonstrated in this case. Lesions are typically hyperpigmented, though cases of associated hypopigmentation or depigmentation have been documented. Affected areas typically fall within the patient’s hand and finger reach, with lesion improvement over several months achievable through trigger avoidance.
 

Pachydermodactyly, a rare but benign fibromatosis around the proximal interphalangeal joints, is often misdiagnosed as juvenile idiopathic arthritis, potentially leading to unnecessary treatments and patient anxiety. Microtrauma history due to digit manipulation is prevalent among affected individuals, with most also exhibiting neuropsychiatric disorders. Histological examination of pachydermodactyly reveals hypergranulosis and dermal thickening, accompanied by increased fibroblasts and collagen types I, III, and V, differing from the epidermal changes seen in LSC.

The differential diagnosis also included phytophotodermatitis, a phototoxic dermatologic reaction following exposure to ultraviolet light subsequent to contact with furocoumarin-containing plant chemicals. However, the persistence of the patient’s lesions for over a year precluded this diagnosis. Secondary hyperpigmentation was also contemplated but excluded due to the absence of preceding inflammatory dermatitis.

Treatment of LSC primarily involves identifying and addressing any underlying conditions, repairing the skin barrier, reducing inflammation, and modifying behaviors contributing to chronic microtrauma, as observed in this patient. Topical corticosteroids may aid in decreasing epidermal thickening and discoloration, though lesion resolution necessitates behavior cessation.

It’s important to identify these types of skin changes in children to avoid unnecessary medical treatments for these benign conditions.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

Suggested Reading

Seier JA, Dissemond J. Lichen Simplex Chronicus Due to Mechanical Irritation. Dtsch Arztebl Int. 2022 Nov 18;119(46):802. doi: 10.3238/arztebl.m2022.0213.

Small S et al. A 12-Year-Old Boy Presenting With Unilateral Proximal Interphalangeal Joint Swelling. BMJ Case Rep. 2011 Apr 13:2011:bcr0120113719. doi: 10.1136/bcr.01.2011.3719.

Voicu C et al Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade. Open Access Maced J Med Sci. 2017 Jul 24;5(4):556-557. doi: 10.3889/oamjms.2017.133.

TOPLINE:

Inflammatory arthritis (IA) occurred in one-third of patients with systemic sclerosis (SSc) in a large observational study and was significantly associated with poor quality of life and physical function, as well as diffuse disease, musculoskeletal manifestations, myositis, and sicca.

METHODOLOGY:

• Researchers reviewed data from 1717 adults with SSc who were enrolled in the Australian  Cohort Study to identify those with IA, defined as the presence of synovitis in one or more joints on clinical examination documented by the treating physician.
• The primary outcome was health-related quality of life (HRQoL) based on patient reports using the Medical Outcomes Short Form 36 and Patient-Reported Outcomes Measurement Information System, and physical function measured with the Health Assessment Questionnaire.

TAKEAWAY:

• IA was identified in 33.3% of the study participants over a median of 4.3 years’ follow-up. IA occurred at a median age of about 60 years and after a median SSc disease duration of 7.9 years. No significant differences in baseline demographics appeared between patients with and without IA.
• Patients with IA had significantly increased risk for diffuse cutaneous SSc (odds ratio [OR], 1.33), concurrent musculoskeletal manifestations such as tendon friction rubs and joint contractures (OR, 1.70), myositis (OR, 2.11), and sicca symptoms (OR, 1.57), compared with those without.
• Patients with IA reported significantly lower HRQoL scores and significantly greater physical disability, compared with those who did not have IA (P < .001 for both).
• IA was significantly less common among patients with , compared with those without pulmonary arterial hypertension (7.2% vs 11.3%; P = .007).

IN PRACTICE:

“Recognizing the presence of IA in SSc is an important first step, as its treatment and monitoring may alleviate some of the associated morbidity,” the researchers wrote.

SOURCE:

The lead author of the study was Eric Schwender, a medical student at the Royal College of Surgeons in Ireland, Dublin, Ireland. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The inability to assess distribution and severity of IA limited the results, as did the inability to assess the impact of disease-modifying antirheumatic drugs in patients with IA.

DISCLOSURES:

The study was supported by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia, and Pfizer, as well as grants to several researchers from the National Health and Medical Research Council of Australia. Lead author Mr. Schwender had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Inflammatory arthritis (IA) occurred in one-third of patients with systemic sclerosis (SSc) in a large observational study and was significantly associated with poor quality of life and physical function, as well as diffuse disease, musculoskeletal manifestations, myositis, and sicca.

METHODOLOGY:

• Researchers reviewed data from 1717 adults with SSc who were enrolled in the Australian  Cohort Study to identify those with IA, defined as the presence of synovitis in one or more joints on clinical examination documented by the treating physician.
• The primary outcome was health-related quality of life (HRQoL) based on patient reports using the Medical Outcomes Short Form 36 and Patient-Reported Outcomes Measurement Information System, and physical function measured with the Health Assessment Questionnaire.

TAKEAWAY:

• IA was identified in 33.3% of the study participants over a median of 4.3 years’ follow-up. IA occurred at a median age of about 60 years and after a median SSc disease duration of 7.9 years. No significant differences in baseline demographics appeared between patients with and without IA.
• Patients with IA had significantly increased risk for diffuse cutaneous SSc (odds ratio [OR], 1.33), concurrent musculoskeletal manifestations such as tendon friction rubs and joint contractures (OR, 1.70), myositis (OR, 2.11), and sicca symptoms (OR, 1.57), compared with those without.
• Patients with IA reported significantly lower HRQoL scores and significantly greater physical disability, compared with those who did not have IA (P < .001 for both).
• IA was significantly less common among patients with , compared with those without pulmonary arterial hypertension (7.2% vs 11.3%; P = .007).

IN PRACTICE:

“Recognizing the presence of IA in SSc is an important first step, as its treatment and monitoring may alleviate some of the associated morbidity,” the researchers wrote.

SOURCE:

The lead author of the study was Eric Schwender, a medical student at the Royal College of Surgeons in Ireland, Dublin, Ireland. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The inability to assess distribution and severity of IA limited the results, as did the inability to assess the impact of disease-modifying antirheumatic drugs in patients with IA.

DISCLOSURES:

The study was supported by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia, and Pfizer, as well as grants to several researchers from the National Health and Medical Research Council of Australia. Lead author Mr. Schwender had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Inflammatory arthritis (IA) occurred in one-third of patients with systemic sclerosis (SSc) in a large observational study and was significantly associated with poor quality of life and physical function, as well as diffuse disease, musculoskeletal manifestations, myositis, and sicca.

METHODOLOGY:

• Researchers reviewed data from 1717 adults with SSc who were enrolled in the Australian  Cohort Study to identify those with IA, defined as the presence of synovitis in one or more joints on clinical examination documented by the treating physician.
• The primary outcome was health-related quality of life (HRQoL) based on patient reports using the Medical Outcomes Short Form 36 and Patient-Reported Outcomes Measurement Information System, and physical function measured with the Health Assessment Questionnaire.

TAKEAWAY:

• IA was identified in 33.3% of the study participants over a median of 4.3 years’ follow-up. IA occurred at a median age of about 60 years and after a median SSc disease duration of 7.9 years. No significant differences in baseline demographics appeared between patients with and without IA.
• Patients with IA had significantly increased risk for diffuse cutaneous SSc (odds ratio [OR], 1.33), concurrent musculoskeletal manifestations such as tendon friction rubs and joint contractures (OR, 1.70), myositis (OR, 2.11), and sicca symptoms (OR, 1.57), compared with those without.
• Patients with IA reported significantly lower HRQoL scores and significantly greater physical disability, compared with those who did not have IA (P < .001 for both).
• IA was significantly less common among patients with , compared with those without pulmonary arterial hypertension (7.2% vs 11.3%; P = .007).

IN PRACTICE:

“Recognizing the presence of IA in SSc is an important first step, as its treatment and monitoring may alleviate some of the associated morbidity,” the researchers wrote.

SOURCE:

The lead author of the study was Eric Schwender, a medical student at the Royal College of Surgeons in Ireland, Dublin, Ireland. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The inability to assess distribution and severity of IA limited the results, as did the inability to assess the impact of disease-modifying antirheumatic drugs in patients with IA.

DISCLOSURES:

The study was supported by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia, and Pfizer, as well as grants to several researchers from the National Health and Medical Research Council of Australia. Lead author Mr. Schwender had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Ashley Winter, MD, remembers the first time she Googled the skin condition lichen sclerosus. Most of the websites listed the autoimmune condition as a rare disease.

In the realm of genital health, some conditions remain shrouded in silence and consequently are more likely to go undercounted and underdiagnosed, said Dr. Winter, a urologist based in Los Angeles.

“I truly believe that we just miss the diagnosis a vast majority of the time because there isn’t enough training on [detecting] it,” said Dr. Winter.

Lichen sclerosus primarily affects the skin in the genital and anal regions. Estimates of the disease range between 1 in 300 and 1 in 1000 people, according to the US National Institutes of Health. The condition also more commonly occurs among women, and symptoms include hypopigmentation, itching, pain, changes in skin appearance, and skin atrophy.

“Most cases [affect the] genital [area] only, so often patients don’t bring it up because they don’t want to be examined,” said Sarah Lonowski, MD, assistant professor of dermatology and codirector of the Multidisciplinary Autoimmune Skin Disease/Derm-Rheum Program at the University of Nebraska–Lincoln. “It’s a sensitive area, it’s an uncomfortable area to have examined, so it comes with a lot of emotional burden,” for patients, Dr. Lonowski said.

Receiving a lichen sclerosis diagnosis can take 5 years or longer, in part because the condition’s symptoms can lead clinicians to first make a diagnosis of a yeast infection or bacterial vaginosis, according to Christina Kraus, MD, assistant professor of dermatology at UCI Health in Irvine, California.

“There is still limited information on this condition in medical education, and it is not uncommon for clinicians who are not in dermatology or gynecology to be unfamiliar with this diagnosis,” Dr. Kraus said.

Because no medical tests are available to confirm lichen sclerosus, clinicians diagnose the condition based on the skin’s appearance and symptoms. In some cases, a skin biopsy may help differentiate it from similar rashes that occur in the genital area.

Prepubescent children and postmenopausal women are most likely to develop genital lichen sclerosis, so pediatricians and primary care physicians may be the first to see possible cases, Dr. Lonowski said.

Patients “may not mention it unless they’re asked,” Dr. Lonowski said, adding clinicians can inquire with patients about genital health, examine bothersome areas, “and refer if you’re not sure.”

Clinicians may also miss the condition during physical exams if they do not examine the vulvar skin, she said. The exact cause also remains elusive, but researchers believe genetic and hormonal factors, as well as an overactive immune response, may contribute to development of the condition.
 

Watch Out for Presentation

While lichen sclerosus more frequently occurs in women, men are also affected by the condition. Benjamin N. Breyer, MD, professor and chair of urology at the University of California San Francisco, said lichen sclerosus is one of the most common skin conditions he treats in his male patients.

“Advanced cases can cause urethral narrowing, which is a condition I treat commonly,” said Dr. Breyer. “Lichen sclerosus is often an underrecognized cause of pain or tearing with erections and sex in men.”

Similar to women, lichen sclerosus presents as white color changes on the skin. For men, the condition can also result in fusion of the shaft skin to the head of the penis and burying or concealment of the penis, Dr. Breyer said.

“This leads to challenges with intimacy and urination and can have extensive impacts on quality of life,” said Dr. Breyer.

For women, the skin changes often extend to the perianal area and can cause scarring, said Dr. Kraus.

“Early scarring may present as adherence of the labia minora to the labia majora or inability to fully retract the clitoral hood from the clitoris,” said Dr. Kraus.

In both men and women, lichen sclerosus and another autoimmune condition known as morphea, characterized by skin hardening and discoloration, often present together, said Dr. Lonowski.

“If you have a patient with known morphea, it’s important to ask about genital symptoms,” said Dr. Lonowski. “The association between the two is fairly strong.”

Circumcision is often the first step to help prevent chronic inflammation among male patients, said Dr. Breyer. Because lichen sclerosus is associated with an increased risk for penile cancer, “it is important to biopsy suspicious lesions,” Dr. Breyer added.

Increasing awareness of lichen sclerosus is crucial for early detection and timely intervention, said Dr. Lonowski. The first-line treatment of genital lichen sclerosus is strong topical steroid ointments to reduce inflammation. Clinicians might prescribe this treatment for use twice daily for 2-3 months and then assesses the patient on their response.

“It is fairly responsive to treatment in most cases,” said Dr. Lonowski.

Once symptoms have improved, Dr. Lonowski transitions patients to a maintenance regimen, which might include using the same steroid but only three times a week, switching to a topical with a less potent steroid dosage, or using a combination of a topical steroid and a nonsteroidal anti-inflammatory cream. Despite the prolonged use of the drug, she said patients with lichen sclerosus usually do not present with side effects like discoloration or thinning of skin.

“You may achieve control or remission, but we don’t stop treatment completely because we know the natural history of the disease is to have flares and recurrence.”

If left untreated, the condition can lead to atrophy, scarring, and distortion of the genital anatomy and, in some cases, develop into squamous cell carcinoma.

“The fact that you can do a topical cream intervention and prevent cancer is huge,” said Dr. Winter.

She said open discussions surrounding genital health led by primary care providers can destigmatize conditions like lichen sclerosus and promote early detection and management.

“We need to foster an environment where individuals feel comfortable discussing their symptoms openly,” Dr. Winter said. “Increased awareness can pave the way for early detection, which is crucial for managing the condition effectively.”

The experts included in the story reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Ashley Winter, MD, remembers the first time she Googled the skin condition lichen sclerosus. Most of the websites listed the autoimmune condition as a rare disease.

In the realm of genital health, some conditions remain shrouded in silence and consequently are more likely to go undercounted and underdiagnosed, said Dr. Winter, a urologist based in Los Angeles.

“I truly believe that we just miss the diagnosis a vast majority of the time because there isn’t enough training on [detecting] it,” said Dr. Winter.

Lichen sclerosus primarily affects the skin in the genital and anal regions. Estimates of the disease range between 1 in 300 and 1 in 1000 people, according to the US National Institutes of Health. The condition also more commonly occurs among women, and symptoms include hypopigmentation, itching, pain, changes in skin appearance, and skin atrophy.

“Most cases [affect the] genital [area] only, so often patients don’t bring it up because they don’t want to be examined,” said Sarah Lonowski, MD, assistant professor of dermatology and codirector of the Multidisciplinary Autoimmune Skin Disease/Derm-Rheum Program at the University of Nebraska–Lincoln. “It’s a sensitive area, it’s an uncomfortable area to have examined, so it comes with a lot of emotional burden,” for patients, Dr. Lonowski said.

Receiving a lichen sclerosis diagnosis can take 5 years or longer, in part because the condition’s symptoms can lead clinicians to first make a diagnosis of a yeast infection or bacterial vaginosis, according to Christina Kraus, MD, assistant professor of dermatology at UCI Health in Irvine, California.

“There is still limited information on this condition in medical education, and it is not uncommon for clinicians who are not in dermatology or gynecology to be unfamiliar with this diagnosis,” Dr. Kraus said.

Because no medical tests are available to confirm lichen sclerosus, clinicians diagnose the condition based on the skin’s appearance and symptoms. In some cases, a skin biopsy may help differentiate it from similar rashes that occur in the genital area.

Prepubescent children and postmenopausal women are most likely to develop genital lichen sclerosis, so pediatricians and primary care physicians may be the first to see possible cases, Dr. Lonowski said.

Patients “may not mention it unless they’re asked,” Dr. Lonowski said, adding clinicians can inquire with patients about genital health, examine bothersome areas, “and refer if you’re not sure.”

Clinicians may also miss the condition during physical exams if they do not examine the vulvar skin, she said. The exact cause also remains elusive, but researchers believe genetic and hormonal factors, as well as an overactive immune response, may contribute to development of the condition.
 

Watch Out for Presentation

While lichen sclerosus more frequently occurs in women, men are also affected by the condition. Benjamin N. Breyer, MD, professor and chair of urology at the University of California San Francisco, said lichen sclerosus is one of the most common skin conditions he treats in his male patients.

“Advanced cases can cause urethral narrowing, which is a condition I treat commonly,” said Dr. Breyer. “Lichen sclerosus is often an underrecognized cause of pain or tearing with erections and sex in men.”

Similar to women, lichen sclerosus presents as white color changes on the skin. For men, the condition can also result in fusion of the shaft skin to the head of the penis and burying or concealment of the penis, Dr. Breyer said.

“This leads to challenges with intimacy and urination and can have extensive impacts on quality of life,” said Dr. Breyer.

For women, the skin changes often extend to the perianal area and can cause scarring, said Dr. Kraus.

“Early scarring may present as adherence of the labia minora to the labia majora or inability to fully retract the clitoral hood from the clitoris,” said Dr. Kraus.

In both men and women, lichen sclerosus and another autoimmune condition known as morphea, characterized by skin hardening and discoloration, often present together, said Dr. Lonowski.

“If you have a patient with known morphea, it’s important to ask about genital symptoms,” said Dr. Lonowski. “The association between the two is fairly strong.”

Circumcision is often the first step to help prevent chronic inflammation among male patients, said Dr. Breyer. Because lichen sclerosus is associated with an increased risk for penile cancer, “it is important to biopsy suspicious lesions,” Dr. Breyer added.

Increasing awareness of lichen sclerosus is crucial for early detection and timely intervention, said Dr. Lonowski. The first-line treatment of genital lichen sclerosus is strong topical steroid ointments to reduce inflammation. Clinicians might prescribe this treatment for use twice daily for 2-3 months and then assesses the patient on their response.

“It is fairly responsive to treatment in most cases,” said Dr. Lonowski.

Once symptoms have improved, Dr. Lonowski transitions patients to a maintenance regimen, which might include using the same steroid but only three times a week, switching to a topical with a less potent steroid dosage, or using a combination of a topical steroid and a nonsteroidal anti-inflammatory cream. Despite the prolonged use of the drug, she said patients with lichen sclerosus usually do not present with side effects like discoloration or thinning of skin.

“You may achieve control or remission, but we don’t stop treatment completely because we know the natural history of the disease is to have flares and recurrence.”

If left untreated, the condition can lead to atrophy, scarring, and distortion of the genital anatomy and, in some cases, develop into squamous cell carcinoma.

“The fact that you can do a topical cream intervention and prevent cancer is huge,” said Dr. Winter.

She said open discussions surrounding genital health led by primary care providers can destigmatize conditions like lichen sclerosus and promote early detection and management.

“We need to foster an environment where individuals feel comfortable discussing their symptoms openly,” Dr. Winter said. “Increased awareness can pave the way for early detection, which is crucial for managing the condition effectively.”

The experts included in the story reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Ashley Winter, MD, remembers the first time she Googled the skin condition lichen sclerosus. Most of the websites listed the autoimmune condition as a rare disease.

In the realm of genital health, some conditions remain shrouded in silence and consequently are more likely to go undercounted and underdiagnosed, said Dr. Winter, a urologist based in Los Angeles.

“I truly believe that we just miss the diagnosis a vast majority of the time because there isn’t enough training on [detecting] it,” said Dr. Winter.

Lichen sclerosus primarily affects the skin in the genital and anal regions. Estimates of the disease range between 1 in 300 and 1 in 1000 people, according to the US National Institutes of Health. The condition also more commonly occurs among women, and symptoms include hypopigmentation, itching, pain, changes in skin appearance, and skin atrophy.

“Most cases [affect the] genital [area] only, so often patients don’t bring it up because they don’t want to be examined,” said Sarah Lonowski, MD, assistant professor of dermatology and codirector of the Multidisciplinary Autoimmune Skin Disease/Derm-Rheum Program at the University of Nebraska–Lincoln. “It’s a sensitive area, it’s an uncomfortable area to have examined, so it comes with a lot of emotional burden,” for patients, Dr. Lonowski said.

Receiving a lichen sclerosis diagnosis can take 5 years or longer, in part because the condition’s symptoms can lead clinicians to first make a diagnosis of a yeast infection or bacterial vaginosis, according to Christina Kraus, MD, assistant professor of dermatology at UCI Health in Irvine, California.

“There is still limited information on this condition in medical education, and it is not uncommon for clinicians who are not in dermatology or gynecology to be unfamiliar with this diagnosis,” Dr. Kraus said.

Because no medical tests are available to confirm lichen sclerosus, clinicians diagnose the condition based on the skin’s appearance and symptoms. In some cases, a skin biopsy may help differentiate it from similar rashes that occur in the genital area.

Prepubescent children and postmenopausal women are most likely to develop genital lichen sclerosis, so pediatricians and primary care physicians may be the first to see possible cases, Dr. Lonowski said.

Patients “may not mention it unless they’re asked,” Dr. Lonowski said, adding clinicians can inquire with patients about genital health, examine bothersome areas, “and refer if you’re not sure.”

Clinicians may also miss the condition during physical exams if they do not examine the vulvar skin, she said. The exact cause also remains elusive, but researchers believe genetic and hormonal factors, as well as an overactive immune response, may contribute to development of the condition.
 

Watch Out for Presentation

While lichen sclerosus more frequently occurs in women, men are also affected by the condition. Benjamin N. Breyer, MD, professor and chair of urology at the University of California San Francisco, said lichen sclerosus is one of the most common skin conditions he treats in his male patients.

“Advanced cases can cause urethral narrowing, which is a condition I treat commonly,” said Dr. Breyer. “Lichen sclerosus is often an underrecognized cause of pain or tearing with erections and sex in men.”

Similar to women, lichen sclerosus presents as white color changes on the skin. For men, the condition can also result in fusion of the shaft skin to the head of the penis and burying or concealment of the penis, Dr. Breyer said.

“This leads to challenges with intimacy and urination and can have extensive impacts on quality of life,” said Dr. Breyer.

For women, the skin changes often extend to the perianal area and can cause scarring, said Dr. Kraus.

“Early scarring may present as adherence of the labia minora to the labia majora or inability to fully retract the clitoral hood from the clitoris,” said Dr. Kraus.

In both men and women, lichen sclerosus and another autoimmune condition known as morphea, characterized by skin hardening and discoloration, often present together, said Dr. Lonowski.

“If you have a patient with known morphea, it’s important to ask about genital symptoms,” said Dr. Lonowski. “The association between the two is fairly strong.”

Circumcision is often the first step to help prevent chronic inflammation among male patients, said Dr. Breyer. Because lichen sclerosus is associated with an increased risk for penile cancer, “it is important to biopsy suspicious lesions,” Dr. Breyer added.

Increasing awareness of lichen sclerosus is crucial for early detection and timely intervention, said Dr. Lonowski. The first-line treatment of genital lichen sclerosus is strong topical steroid ointments to reduce inflammation. Clinicians might prescribe this treatment for use twice daily for 2-3 months and then assesses the patient on their response.

“It is fairly responsive to treatment in most cases,” said Dr. Lonowski.

Once symptoms have improved, Dr. Lonowski transitions patients to a maintenance regimen, which might include using the same steroid but only three times a week, switching to a topical with a less potent steroid dosage, or using a combination of a topical steroid and a nonsteroidal anti-inflammatory cream. Despite the prolonged use of the drug, she said patients with lichen sclerosus usually do not present with side effects like discoloration or thinning of skin.

“You may achieve control or remission, but we don’t stop treatment completely because we know the natural history of the disease is to have flares and recurrence.”

If left untreated, the condition can lead to atrophy, scarring, and distortion of the genital anatomy and, in some cases, develop into squamous cell carcinoma.

“The fact that you can do a topical cream intervention and prevent cancer is huge,” said Dr. Winter.

She said open discussions surrounding genital health led by primary care providers can destigmatize conditions like lichen sclerosus and promote early detection and management.

“We need to foster an environment where individuals feel comfortable discussing their symptoms openly,” Dr. Winter said. “Increased awareness can pave the way for early detection, which is crucial for managing the condition effectively.”

The experts included in the story reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.