MDedge Dermatology

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. In this retrospective analysis, we evaluated recurrence rates of BCC of the ear in 102 patients who underwent treatment with Mohs micrographic surgery (MMS) or radiation therapy (RT) at a single institution between January 2017 and December 2019. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. Recurrence rates were assessed over a mean follow-up time of 2.8 years. Although MMS is the gold standard for treatment of BCC of the ear, RT may be a suitable alternative for nonsurgical candidates.

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. Given that these aggressive histologic subtypes—defined as morpheaform, basosquamous, sclerosing, infiltrative, or micronodular in any portion of the tumor—have been reported as independent predictors of recurrence,^1,2 BCC of the ear may be more likely to recur.

Mohs micrographic surgery (MMS) is the gold standard for the treatment of BCC of the ear. For nonsurgical candidates—those with high bleeding risk, low life expectancy, or other medical or social factors—definitive radiation therapy (RT) may be an option. Our study sought to examine recurrence rates in patients with BCC of the ear treated with MMS vs RT.

Methods

A retrospective review of patients undergoing treatment of BCC of the ear at Bighorn Mohs Surgery and Dermatology Center (San Diego, California) between January 2017 and December 2019 was conducted. A total of 507 medical records were reviewed, and 102 patients were included in the study. Inclusion criteria consisted of biopsy-confirmed BCC of the ear that was treated with MMS, RT, or both. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. This retrospective review of medical records was exempt from institutional review board approval, as it did not involve direct human research subjects, solely entailing a retrospective examination of existing data.

Results

Of the 102 patients included, 82 were male and 20 were female, with an average age of 71 years. All patients were White with the exception of 1 patient whose race was unknown. Two patients were immunocompromised. The helix was identified as the most frequently involved site on the ear (Table). Most of the tumors (56/102) exhibited aggressive histologic subtypes; 36 tumors had nonaggressive histology, and 10 had no subtype listed. Two of the BCCs demonstrated perineural invasion on biopsy. Mohs micrographic surgery was used to treat 96 BCCs, definitive RT was used to treat 5 BCCs (all of which occurred in nonsurgical candidates), and MMS and adjuvant RT were used in 1 patient given multifocal perineural involvement. All 5 patients treated with definitive RT received electron beam radiation therapy; the total dose ranged from 5100 to 6000 cGy divided into 17 to 24 fractions. The final MMS defects ranged from 6 to 55 mm in size. The average follow-up time was 2.8 years. One of the BCCs on the helix that was treated with MMS recurred after 1.3 years. The overall recurrence rate was 0.98%. None of the patients treated with definitive RT experienced recurrence after the mean follow-up time of 2.8 years.

Comment

Basal cell carcinoma is the most commonly diagnosed cancer in the United States, with approximately 2 million new cases each year.¹ Treatment modalities for localized BCC include MMS, surgical excision, electrodesiccation and curettage, topical and intralesional medications, laser therapy, and RT. For high-risk BCCs, MMS is associated with the lowest recurrence rates⁴ and remains the gold standard for treatment. For patients with contraindications to surgery, definitive RT is an alternative treatment for high-risk BCC.¹

Definitive RT can be employed for patients who are poor surgical candidates or when surgery would result in substantial morbidity, impaired function, and/or poor cosmesis.³ Radiation therapy for skin cancers of the ear commonly is administered using high-energy electrons that produce double-strand breaks in the DNA of malignant cells, leading to cell death.⁴ Disadvantages of RT compared to MMS include a longer treatment course (3 to 6 weeks), possible minimal long-term cosmetic sequelae (eg, color or texture mismatch), lack of pathologic confirmation of margin control, and small risk for secondary malignancy in the treatment field over 2 to 3 decades. For patients with incurable or metastatic disease, palliative RT can provide local control and/or symptomatic relief to improve quality of life.⁴ Adjuvant RT may be indicated if there is substantial perineural involvement or positive margins after MMS when margins are unable to be achieved or in patients who may not tolerate prolonged or extensive surgical procedures.³

Basal cell carcinoma of the ear is considered a high-risk anatomic location independent of other prognostic factors. Basal cell carcinomas of the ear have a higher propensity for more aggressive histologic subtypes and subclinical spread.⁵ Our study demonstrated a higher proportion of aggressive histologic subtypes (56/102 [54.9%]) compared with nonaggressive subtypes (36/102 [35.3%]). There was 1 recurrence of a nodular, sclerosing, and infiltrative BCC on the helix treated with MMS after 1.3 years.

Limitations of our study include that it was conducted at a single institution with a homogenous study population and with relatively short follow-up.

Conclusion

Our study further validates the well-known utility of MMS for the treatment of BCC of the ears. Definitive RT is a suitable alternative for patients who are not surgical candidates. Adjuvant RT may be considered for substantial perineural involvement or positive margins after MMS.³

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. In this retrospective analysis, we evaluated recurrence rates of BCC of the ear in 102 patients who underwent treatment with Mohs micrographic surgery (MMS) or radiation therapy (RT) at a single institution between January 2017 and December 2019. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. Recurrence rates were assessed over a mean follow-up time of 2.8 years. Although MMS is the gold standard for treatment of BCC of the ear, RT may be a suitable alternative for nonsurgical candidates.

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. Given that these aggressive histologic subtypes—defined as morpheaform, basosquamous, sclerosing, infiltrative, or micronodular in any portion of the tumor—have been reported as independent predictors of recurrence,^1,2 BCC of the ear may be more likely to recur.

Mohs micrographic surgery (MMS) is the gold standard for the treatment of BCC of the ear. For nonsurgical candidates—those with high bleeding risk, low life expectancy, or other medical or social factors—definitive radiation therapy (RT) may be an option. Our study sought to examine recurrence rates in patients with BCC of the ear treated with MMS vs RT.

Methods

A retrospective review of patients undergoing treatment of BCC of the ear at Bighorn Mohs Surgery and Dermatology Center (San Diego, California) between January 2017 and December 2019 was conducted. A total of 507 medical records were reviewed, and 102 patients were included in the study. Inclusion criteria consisted of biopsy-confirmed BCC of the ear that was treated with MMS, RT, or both. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. This retrospective review of medical records was exempt from institutional review board approval, as it did not involve direct human research subjects, solely entailing a retrospective examination of existing data.

Results

Of the 102 patients included, 82 were male and 20 were female, with an average age of 71 years. All patients were White with the exception of 1 patient whose race was unknown. Two patients were immunocompromised. The helix was identified as the most frequently involved site on the ear (Table). Most of the tumors (56/102) exhibited aggressive histologic subtypes; 36 tumors had nonaggressive histology, and 10 had no subtype listed. Two of the BCCs demonstrated perineural invasion on biopsy. Mohs micrographic surgery was used to treat 96 BCCs, definitive RT was used to treat 5 BCCs (all of which occurred in nonsurgical candidates), and MMS and adjuvant RT were used in 1 patient given multifocal perineural involvement. All 5 patients treated with definitive RT received electron beam radiation therapy; the total dose ranged from 5100 to 6000 cGy divided into 17 to 24 fractions. The final MMS defects ranged from 6 to 55 mm in size. The average follow-up time was 2.8 years. One of the BCCs on the helix that was treated with MMS recurred after 1.3 years. The overall recurrence rate was 0.98%. None of the patients treated with definitive RT experienced recurrence after the mean follow-up time of 2.8 years.

Comment

Basal cell carcinoma is the most commonly diagnosed cancer in the United States, with approximately 2 million new cases each year.¹ Treatment modalities for localized BCC include MMS, surgical excision, electrodesiccation and curettage, topical and intralesional medications, laser therapy, and RT. For high-risk BCCs, MMS is associated with the lowest recurrence rates⁴ and remains the gold standard for treatment. For patients with contraindications to surgery, definitive RT is an alternative treatment for high-risk BCC.¹

Definitive RT can be employed for patients who are poor surgical candidates or when surgery would result in substantial morbidity, impaired function, and/or poor cosmesis.³ Radiation therapy for skin cancers of the ear commonly is administered using high-energy electrons that produce double-strand breaks in the DNA of malignant cells, leading to cell death.⁴ Disadvantages of RT compared to MMS include a longer treatment course (3 to 6 weeks), possible minimal long-term cosmetic sequelae (eg, color or texture mismatch), lack of pathologic confirmation of margin control, and small risk for secondary malignancy in the treatment field over 2 to 3 decades. For patients with incurable or metastatic disease, palliative RT can provide local control and/or symptomatic relief to improve quality of life.⁴ Adjuvant RT may be indicated if there is substantial perineural involvement or positive margins after MMS when margins are unable to be achieved or in patients who may not tolerate prolonged or extensive surgical procedures.³

Basal cell carcinoma of the ear is considered a high-risk anatomic location independent of other prognostic factors. Basal cell carcinomas of the ear have a higher propensity for more aggressive histologic subtypes and subclinical spread.⁵ Our study demonstrated a higher proportion of aggressive histologic subtypes (56/102 [54.9%]) compared with nonaggressive subtypes (36/102 [35.3%]). There was 1 recurrence of a nodular, sclerosing, and infiltrative BCC on the helix treated with MMS after 1.3 years.

Limitations of our study include that it was conducted at a single institution with a homogenous study population and with relatively short follow-up.

Conclusion

Our study further validates the well-known utility of MMS for the treatment of BCC of the ears. Definitive RT is a suitable alternative for patients who are not surgical candidates. Adjuvant RT may be considered for substantial perineural involvement or positive margins after MMS.³

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. In this retrospective analysis, we evaluated recurrence rates of BCC of the ear in 102 patients who underwent treatment with Mohs micrographic surgery (MMS) or radiation therapy (RT) at a single institution between January 2017 and December 2019. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. Recurrence rates were assessed over a mean follow-up time of 2.8 years. Although MMS is the gold standard for treatment of BCC of the ear, RT may be a suitable alternative for nonsurgical candidates.

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. Given that these aggressive histologic subtypes—defined as morpheaform, basosquamous, sclerosing, infiltrative, or micronodular in any portion of the tumor—have been reported as independent predictors of recurrence,^1,2 BCC of the ear may be more likely to recur.

Mohs micrographic surgery (MMS) is the gold standard for the treatment of BCC of the ear. For nonsurgical candidates—those with high bleeding risk, low life expectancy, or other medical or social factors—definitive radiation therapy (RT) may be an option. Our study sought to examine recurrence rates in patients with BCC of the ear treated with MMS vs RT.

Methods

A retrospective review of patients undergoing treatment of BCC of the ear at Bighorn Mohs Surgery and Dermatology Center (San Diego, California) between January 2017 and December 2019 was conducted. A total of 507 medical records were reviewed, and 102 patients were included in the study. Inclusion criteria consisted of biopsy-confirmed BCC of the ear that was treated with MMS, RT, or both. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. This retrospective review of medical records was exempt from institutional review board approval, as it did not involve direct human research subjects, solely entailing a retrospective examination of existing data.

Results

Of the 102 patients included, 82 were male and 20 were female, with an average age of 71 years. All patients were White with the exception of 1 patient whose race was unknown. Two patients were immunocompromised. The helix was identified as the most frequently involved site on the ear (Table). Most of the tumors (56/102) exhibited aggressive histologic subtypes; 36 tumors had nonaggressive histology, and 10 had no subtype listed. Two of the BCCs demonstrated perineural invasion on biopsy. Mohs micrographic surgery was used to treat 96 BCCs, definitive RT was used to treat 5 BCCs (all of which occurred in nonsurgical candidates), and MMS and adjuvant RT were used in 1 patient given multifocal perineural involvement. All 5 patients treated with definitive RT received electron beam radiation therapy; the total dose ranged from 5100 to 6000 cGy divided into 17 to 24 fractions. The final MMS defects ranged from 6 to 55 mm in size. The average follow-up time was 2.8 years. One of the BCCs on the helix that was treated with MMS recurred after 1.3 years. The overall recurrence rate was 0.98%. None of the patients treated with definitive RT experienced recurrence after the mean follow-up time of 2.8 years.

Comment

Basal cell carcinoma is the most commonly diagnosed cancer in the United States, with approximately 2 million new cases each year.¹ Treatment modalities for localized BCC include MMS, surgical excision, electrodesiccation and curettage, topical and intralesional medications, laser therapy, and RT. For high-risk BCCs, MMS is associated with the lowest recurrence rates⁴ and remains the gold standard for treatment. For patients with contraindications to surgery, definitive RT is an alternative treatment for high-risk BCC.¹

Definitive RT can be employed for patients who are poor surgical candidates or when surgery would result in substantial morbidity, impaired function, and/or poor cosmesis.³ Radiation therapy for skin cancers of the ear commonly is administered using high-energy electrons that produce double-strand breaks in the DNA of malignant cells, leading to cell death.⁴ Disadvantages of RT compared to MMS include a longer treatment course (3 to 6 weeks), possible minimal long-term cosmetic sequelae (eg, color or texture mismatch), lack of pathologic confirmation of margin control, and small risk for secondary malignancy in the treatment field over 2 to 3 decades. For patients with incurable or metastatic disease, palliative RT can provide local control and/or symptomatic relief to improve quality of life.⁴ Adjuvant RT may be indicated if there is substantial perineural involvement or positive margins after MMS when margins are unable to be achieved or in patients who may not tolerate prolonged or extensive surgical procedures.³

Basal cell carcinoma of the ear is considered a high-risk anatomic location independent of other prognostic factors. Basal cell carcinomas of the ear have a higher propensity for more aggressive histologic subtypes and subclinical spread.⁵ Our study demonstrated a higher proportion of aggressive histologic subtypes (56/102 [54.9%]) compared with nonaggressive subtypes (36/102 [35.3%]). There was 1 recurrence of a nodular, sclerosing, and infiltrative BCC on the helix treated with MMS after 1.3 years.

Limitations of our study include that it was conducted at a single institution with a homogenous study population and with relatively short follow-up.

Conclusion

Our study further validates the well-known utility of MMS for the treatment of BCC of the ears. Definitive RT is a suitable alternative for patients who are not surgical candidates. Adjuvant RT may be considered for substantial perineural involvement or positive margins after MMS.³

With the increasing utilization of telemedicine since the COVID-19 pandemic, it is critical that clinicians have an appropriate understanding of the application of virtual care resources, including teledermatology. We present a case series of 3 patients to demonstrate the clinical utility of teledermatology in reducing the time to diagnosis of various rare and/or aggressive cutaneous malignancies, including Merkel cell carcinoma, malignant melanoma, and atypical fibroxanthoma. Cases were obtained from one large Midwestern medical center during the month of July 2021. Each case presented includes a description of the initial teledermatology presentation and reviews the clinical timeline from initial consultation submission to in-person clinic visit with lesion biopsy. This case series demonstrates real-world examples of how teledermatology can be utilized to expedite the care of specific vulnerable patient populations.

Teledermatology is a rapidly growing digital resource with specific utility in triaging patients to determine those requiring in-person evaluation for early and accurate detection of skin malignancies. Approximately one-third of teledermatology consultations result in face-to-face clinical encounters, with malignant neoplasms being the leading cause for biopsy.^1,2 For specific populations, such as geriatric and immunocompromised patients, teledermatology may serve as a valuable tool, particularly in the wake of the COVID-19 pandemic. Furthermore, telemedicine may aid in addressing health disparities within the field of medicine and ultimately may improve access to care for vulnerable populations.³ Along with increasing access to specific subspecialty expertise, the use of teledermatology may reduce health care costs and improve the overall quality of care delivered to patients.^4,5

We describe the clinical utility of teledermatology in triaging and diagnosing skin malignancies through a series of 3 cases obtained from digital image review at one large Midwestern medical center during the month of July 2021. Three unique cases with a final diagnosis of a rare or aggressive skin cancer were selected as examples, including a 75-year-old man with Merkle cell carcinoma, a 55-year-old man with aggressive pT3b malignant melanoma, and a 72-year-old man with an atypical fibroxanthoma. A clinical timeline of each case is presented, including the time intervals from initial image submission to image review, image submission to face-to-face clinical encounter, and image submission to final diagnosis. In all cases, the primary care provider submitted an order for teledermatology, and the teledermatology team obtained the images.

Case Series

Patient 1—Images of the right hand of a 75-year-old man with a medical history of basal cell carcinoma were submitted for teledermatology consultation utilizing store-and-forward image-capturing technology (day 1). The patient history provided with image submission indicated that the lesion had been present for 6 months and there were no associated symptoms. Clinical imaging demonstrated a pink-red pearly papule located on the proximal fourth digit of the dorsal aspect of the right hand (Figure 1). One day following the teledermatology request (day 2), the patient’s case was reviewed and triaged for an in-person visit. The patient was brought to clinic on day 34, and a biopsy was performed. On day 36, dermatopathology results indicated a diagnosis of Merkel cell carcinoma. On day 37, the patient was referred to surgical oncology, and on day 44, the patient underwent an initial surgical oncology visit with a plan for wide local excision of the right fourth digit with right axillary sentinel lymph node biopsy.

Patient 2—Images of the left flank of a 55-year-old man were submitted for teledermatology consultation via store-and-forward technology (day 1). A patient history provided with the image indicated that the lesion had been present for months to years and there were no associated symptoms, but the lesion recently had changed in color and size. Teledermatology images were reviewed on day 3 and demonstrated a 2- to 3-cm brown plaque on the left flank with color variegation and a prominent red papule protruding centrally (Figure 2). The patient was scheduled for an urgent in-person visit with biopsy. On day 6, the patient presented to clinic and an excision biopsy was performed. Dermatopathology was ordered with a RUSH indication, with results on day 7 revealing a pT3b malignant melanoma. An urgent consultation to surgical oncology was placed on the same day, and the patient underwent an initial surgical oncology visit on day 24 with a plan for wide local excision with left axillary and inguinal sentinel lymph node biopsy.

Patient 3—Images of the left ear of a 72-year-old man were submitted for teledermatology consultation utilizing review via store-and-forward technology (day 1). A patient history indicated that the lesion had been present for 3 months with associated bleeding. Image review demonstrated a solitary pearly pink papule located on the crura of the antihelix (Figure 3). Initial teledermatology consultation was reviewed on day 2 with notification of the need for in-person evaluation. The patient presented to clinic on day 33 for a biopsy, with dermatopathology results on day 36 consistent with an atypical fibroxanthoma. The patient was scheduled for Mohs micrographic surgery on day 37 and underwent surgical treatment on day 64.

Comment

Teledermatology consultations from all patients demonstrated adequate image quality to be able to evaluate the lesion of concern and yielded a request for in-person evaluation with possible biopsy (Table). In this case series, the average time interval from teledermatology consultation placement to teledermatology image report was 2 days (range, 1–3 days). The average time from teledermatology consultation placement to face-to-face encounter with biopsy was 24.3 days for the 3 cases presented in this series (range, 6–34 days). The initial surgical oncology visits took place an average of 34 days after the initial teledermatology consultation was placed for the 2 patients requiring referral (44 days for patient 1; 24 days for patient 2). For patient 3, Mohs micrographic surgery was required for treatment, which was scheduled by day 37 and subsequently performed on day 64.

When specifically looking at the diagnosis of cutaneous malignancies, studies have found that the incidence of skin cancer detection is similar for teledermatology compared to in-person clinic visits.^6,7 Creighton-Smith et al⁶ performed a retrospective cohort study comparing prebiopsy and postbiopsy diagnostic accuracy and detection rates of skin cancer between store-and-forward technology and face-to-face consultation. When adjusting for possible compounding factors including personal and family history of skin cancer, there was no notable difference in detection rates of any skin cancer, including melanoma and nonmelanoma skin cancers. Furthermore, the 2 cohorts of patients were found to have similar prebiopsy and postbiopsy diagnostic concordance, with similar times from consultation being placed to requested biopsy and time from biopsy to final treatment.⁶

Clarke et al⁷ similarly analyzed the accuracy of store-and-forward teledermatology and found that there was overall concordance in diagnosis when comparing clinical dermatologists to teledermatologists. Moreover, when melanocytic lesions were excluded from the study, the decision to biopsy did not differ substantially.⁷

Areas of further study include determining what percentage of teledermatology lesions of concern for malignancy were proven to be skin cancer after in-person evaluation and biopsy, as well as investigating the effectiveness of teledermatology for melanocytic lesions, which frequently are removed from analysis in large-scale teledermatology studies.

Although teledermatology has substantial clinical utility and may serve as a great resource for specific populations, including geriatric patients and those who are immunocompromised, it is important to recognize notable limitations. Specifically, brief history and image review should not serve as replacements for a face-to-face visit with physical examination in cases where the diagnosis remains uncertain or when high-risk skin malignancies are suspected or included in the differential. Certain aggressive cutaneous malignancies such as Merkel cell carcinoma may appear as less aggressive via teledermatology due to restrictions of technology.

Conclusion

Teledermatology has had a major impact on the way health care is delivered to patients and may increase access to care, reducing unnecessary in-person visits and decreasing the number of in-person visit no-shows. With the appropriate use of a brief clinical history and image review, teledermatology can be effective to evaluate specific lesions of concern. We report 3 unique cases identified during a 1-month period at a large Midwestern medical center. These cases serve as important examples of the application of teledermatology in reducing the time to diagnosis of aggressive skin malignancies. Further research on the clinical utility of teledermatology is warranted.

Acknowledgments—The authors thank the additional providers from the University of Wisconsin and William S. Middleton Memorial Veterans Hospital (both in Madison, Wisconsin) involved in the medical care of the patients included in this case series.

With the increasing utilization of telemedicine since the COVID-19 pandemic, it is critical that clinicians have an appropriate understanding of the application of virtual care resources, including teledermatology. We present a case series of 3 patients to demonstrate the clinical utility of teledermatology in reducing the time to diagnosis of various rare and/or aggressive cutaneous malignancies, including Merkel cell carcinoma, malignant melanoma, and atypical fibroxanthoma. Cases were obtained from one large Midwestern medical center during the month of July 2021. Each case presented includes a description of the initial teledermatology presentation and reviews the clinical timeline from initial consultation submission to in-person clinic visit with lesion biopsy. This case series demonstrates real-world examples of how teledermatology can be utilized to expedite the care of specific vulnerable patient populations.

Teledermatology is a rapidly growing digital resource with specific utility in triaging patients to determine those requiring in-person evaluation for early and accurate detection of skin malignancies. Approximately one-third of teledermatology consultations result in face-to-face clinical encounters, with malignant neoplasms being the leading cause for biopsy.^1,2 For specific populations, such as geriatric and immunocompromised patients, teledermatology may serve as a valuable tool, particularly in the wake of the COVID-19 pandemic. Furthermore, telemedicine may aid in addressing health disparities within the field of medicine and ultimately may improve access to care for vulnerable populations.³ Along with increasing access to specific subspecialty expertise, the use of teledermatology may reduce health care costs and improve the overall quality of care delivered to patients.^4,5

We describe the clinical utility of teledermatology in triaging and diagnosing skin malignancies through a series of 3 cases obtained from digital image review at one large Midwestern medical center during the month of July 2021. Three unique cases with a final diagnosis of a rare or aggressive skin cancer were selected as examples, including a 75-year-old man with Merkle cell carcinoma, a 55-year-old man with aggressive pT3b malignant melanoma, and a 72-year-old man with an atypical fibroxanthoma. A clinical timeline of each case is presented, including the time intervals from initial image submission to image review, image submission to face-to-face clinical encounter, and image submission to final diagnosis. In all cases, the primary care provider submitted an order for teledermatology, and the teledermatology team obtained the images.

Case Series

Patient 1—Images of the right hand of a 75-year-old man with a medical history of basal cell carcinoma were submitted for teledermatology consultation utilizing store-and-forward image-capturing technology (day 1). The patient history provided with image submission indicated that the lesion had been present for 6 months and there were no associated symptoms. Clinical imaging demonstrated a pink-red pearly papule located on the proximal fourth digit of the dorsal aspect of the right hand (Figure 1). One day following the teledermatology request (day 2), the patient’s case was reviewed and triaged for an in-person visit. The patient was brought to clinic on day 34, and a biopsy was performed. On day 36, dermatopathology results indicated a diagnosis of Merkel cell carcinoma. On day 37, the patient was referred to surgical oncology, and on day 44, the patient underwent an initial surgical oncology visit with a plan for wide local excision of the right fourth digit with right axillary sentinel lymph node biopsy.

Patient 2—Images of the left flank of a 55-year-old man were submitted for teledermatology consultation via store-and-forward technology (day 1). A patient history provided with the image indicated that the lesion had been present for months to years and there were no associated symptoms, but the lesion recently had changed in color and size. Teledermatology images were reviewed on day 3 and demonstrated a 2- to 3-cm brown plaque on the left flank with color variegation and a prominent red papule protruding centrally (Figure 2). The patient was scheduled for an urgent in-person visit with biopsy. On day 6, the patient presented to clinic and an excision biopsy was performed. Dermatopathology was ordered with a RUSH indication, with results on day 7 revealing a pT3b malignant melanoma. An urgent consultation to surgical oncology was placed on the same day, and the patient underwent an initial surgical oncology visit on day 24 with a plan for wide local excision with left axillary and inguinal sentinel lymph node biopsy.

Patient 3—Images of the left ear of a 72-year-old man were submitted for teledermatology consultation utilizing review via store-and-forward technology (day 1). A patient history indicated that the lesion had been present for 3 months with associated bleeding. Image review demonstrated a solitary pearly pink papule located on the crura of the antihelix (Figure 3). Initial teledermatology consultation was reviewed on day 2 with notification of the need for in-person evaluation. The patient presented to clinic on day 33 for a biopsy, with dermatopathology results on day 36 consistent with an atypical fibroxanthoma. The patient was scheduled for Mohs micrographic surgery on day 37 and underwent surgical treatment on day 64.

Comment

Teledermatology consultations from all patients demonstrated adequate image quality to be able to evaluate the lesion of concern and yielded a request for in-person evaluation with possible biopsy (Table). In this case series, the average time interval from teledermatology consultation placement to teledermatology image report was 2 days (range, 1–3 days). The average time from teledermatology consultation placement to face-to-face encounter with biopsy was 24.3 days for the 3 cases presented in this series (range, 6–34 days). The initial surgical oncology visits took place an average of 34 days after the initial teledermatology consultation was placed for the 2 patients requiring referral (44 days for patient 1; 24 days for patient 2). For patient 3, Mohs micrographic surgery was required for treatment, which was scheduled by day 37 and subsequently performed on day 64.

When specifically looking at the diagnosis of cutaneous malignancies, studies have found that the incidence of skin cancer detection is similar for teledermatology compared to in-person clinic visits.^6,7 Creighton-Smith et al⁶ performed a retrospective cohort study comparing prebiopsy and postbiopsy diagnostic accuracy and detection rates of skin cancer between store-and-forward technology and face-to-face consultation. When adjusting for possible compounding factors including personal and family history of skin cancer, there was no notable difference in detection rates of any skin cancer, including melanoma and nonmelanoma skin cancers. Furthermore, the 2 cohorts of patients were found to have similar prebiopsy and postbiopsy diagnostic concordance, with similar times from consultation being placed to requested biopsy and time from biopsy to final treatment.⁶

Clarke et al⁷ similarly analyzed the accuracy of store-and-forward teledermatology and found that there was overall concordance in diagnosis when comparing clinical dermatologists to teledermatologists. Moreover, when melanocytic lesions were excluded from the study, the decision to biopsy did not differ substantially.⁷

Areas of further study include determining what percentage of teledermatology lesions of concern for malignancy were proven to be skin cancer after in-person evaluation and biopsy, as well as investigating the effectiveness of teledermatology for melanocytic lesions, which frequently are removed from analysis in large-scale teledermatology studies.

Although teledermatology has substantial clinical utility and may serve as a great resource for specific populations, including geriatric patients and those who are immunocompromised, it is important to recognize notable limitations. Specifically, brief history and image review should not serve as replacements for a face-to-face visit with physical examination in cases where the diagnosis remains uncertain or when high-risk skin malignancies are suspected or included in the differential. Certain aggressive cutaneous malignancies such as Merkel cell carcinoma may appear as less aggressive via teledermatology due to restrictions of technology.

Conclusion

Teledermatology has had a major impact on the way health care is delivered to patients and may increase access to care, reducing unnecessary in-person visits and decreasing the number of in-person visit no-shows. With the appropriate use of a brief clinical history and image review, teledermatology can be effective to evaluate specific lesions of concern. We report 3 unique cases identified during a 1-month period at a large Midwestern medical center. These cases serve as important examples of the application of teledermatology in reducing the time to diagnosis of aggressive skin malignancies. Further research on the clinical utility of teledermatology is warranted.

Acknowledgments—The authors thank the additional providers from the University of Wisconsin and William S. Middleton Memorial Veterans Hospital (both in Madison, Wisconsin) involved in the medical care of the patients included in this case series.

With the increasing utilization of telemedicine since the COVID-19 pandemic, it is critical that clinicians have an appropriate understanding of the application of virtual care resources, including teledermatology. We present a case series of 3 patients to demonstrate the clinical utility of teledermatology in reducing the time to diagnosis of various rare and/or aggressive cutaneous malignancies, including Merkel cell carcinoma, malignant melanoma, and atypical fibroxanthoma. Cases were obtained from one large Midwestern medical center during the month of July 2021. Each case presented includes a description of the initial teledermatology presentation and reviews the clinical timeline from initial consultation submission to in-person clinic visit with lesion biopsy. This case series demonstrates real-world examples of how teledermatology can be utilized to expedite the care of specific vulnerable patient populations.

Teledermatology is a rapidly growing digital resource with specific utility in triaging patients to determine those requiring in-person evaluation for early and accurate detection of skin malignancies. Approximately one-third of teledermatology consultations result in face-to-face clinical encounters, with malignant neoplasms being the leading cause for biopsy.^1,2 For specific populations, such as geriatric and immunocompromised patients, teledermatology may serve as a valuable tool, particularly in the wake of the COVID-19 pandemic. Furthermore, telemedicine may aid in addressing health disparities within the field of medicine and ultimately may improve access to care for vulnerable populations.³ Along with increasing access to specific subspecialty expertise, the use of teledermatology may reduce health care costs and improve the overall quality of care delivered to patients.^4,5

We describe the clinical utility of teledermatology in triaging and diagnosing skin malignancies through a series of 3 cases obtained from digital image review at one large Midwestern medical center during the month of July 2021. Three unique cases with a final diagnosis of a rare or aggressive skin cancer were selected as examples, including a 75-year-old man with Merkle cell carcinoma, a 55-year-old man with aggressive pT3b malignant melanoma, and a 72-year-old man with an atypical fibroxanthoma. A clinical timeline of each case is presented, including the time intervals from initial image submission to image review, image submission to face-to-face clinical encounter, and image submission to final diagnosis. In all cases, the primary care provider submitted an order for teledermatology, and the teledermatology team obtained the images.

Case Series

Patient 1—Images of the right hand of a 75-year-old man with a medical history of basal cell carcinoma were submitted for teledermatology consultation utilizing store-and-forward image-capturing technology (day 1). The patient history provided with image submission indicated that the lesion had been present for 6 months and there were no associated symptoms. Clinical imaging demonstrated a pink-red pearly papule located on the proximal fourth digit of the dorsal aspect of the right hand (Figure 1). One day following the teledermatology request (day 2), the patient’s case was reviewed and triaged for an in-person visit. The patient was brought to clinic on day 34, and a biopsy was performed. On day 36, dermatopathology results indicated a diagnosis of Merkel cell carcinoma. On day 37, the patient was referred to surgical oncology, and on day 44, the patient underwent an initial surgical oncology visit with a plan for wide local excision of the right fourth digit with right axillary sentinel lymph node biopsy.

Patient 2—Images of the left flank of a 55-year-old man were submitted for teledermatology consultation via store-and-forward technology (day 1). A patient history provided with the image indicated that the lesion had been present for months to years and there were no associated symptoms, but the lesion recently had changed in color and size. Teledermatology images were reviewed on day 3 and demonstrated a 2- to 3-cm brown plaque on the left flank with color variegation and a prominent red papule protruding centrally (Figure 2). The patient was scheduled for an urgent in-person visit with biopsy. On day 6, the patient presented to clinic and an excision biopsy was performed. Dermatopathology was ordered with a RUSH indication, with results on day 7 revealing a pT3b malignant melanoma. An urgent consultation to surgical oncology was placed on the same day, and the patient underwent an initial surgical oncology visit on day 24 with a plan for wide local excision with left axillary and inguinal sentinel lymph node biopsy.

Patient 3—Images of the left ear of a 72-year-old man were submitted for teledermatology consultation utilizing review via store-and-forward technology (day 1). A patient history indicated that the lesion had been present for 3 months with associated bleeding. Image review demonstrated a solitary pearly pink papule located on the crura of the antihelix (Figure 3). Initial teledermatology consultation was reviewed on day 2 with notification of the need for in-person evaluation. The patient presented to clinic on day 33 for a biopsy, with dermatopathology results on day 36 consistent with an atypical fibroxanthoma. The patient was scheduled for Mohs micrographic surgery on day 37 and underwent surgical treatment on day 64.

Comment

Teledermatology consultations from all patients demonstrated adequate image quality to be able to evaluate the lesion of concern and yielded a request for in-person evaluation with possible biopsy (Table). In this case series, the average time interval from teledermatology consultation placement to teledermatology image report was 2 days (range, 1–3 days). The average time from teledermatology consultation placement to face-to-face encounter with biopsy was 24.3 days for the 3 cases presented in this series (range, 6–34 days). The initial surgical oncology visits took place an average of 34 days after the initial teledermatology consultation was placed for the 2 patients requiring referral (44 days for patient 1; 24 days for patient 2). For patient 3, Mohs micrographic surgery was required for treatment, which was scheduled by day 37 and subsequently performed on day 64.

When specifically looking at the diagnosis of cutaneous malignancies, studies have found that the incidence of skin cancer detection is similar for teledermatology compared to in-person clinic visits.^6,7 Creighton-Smith et al⁶ performed a retrospective cohort study comparing prebiopsy and postbiopsy diagnostic accuracy and detection rates of skin cancer between store-and-forward technology and face-to-face consultation. When adjusting for possible compounding factors including personal and family history of skin cancer, there was no notable difference in detection rates of any skin cancer, including melanoma and nonmelanoma skin cancers. Furthermore, the 2 cohorts of patients were found to have similar prebiopsy and postbiopsy diagnostic concordance, with similar times from consultation being placed to requested biopsy and time from biopsy to final treatment.⁶

Clarke et al⁷ similarly analyzed the accuracy of store-and-forward teledermatology and found that there was overall concordance in diagnosis when comparing clinical dermatologists to teledermatologists. Moreover, when melanocytic lesions were excluded from the study, the decision to biopsy did not differ substantially.⁷

Areas of further study include determining what percentage of teledermatology lesions of concern for malignancy were proven to be skin cancer after in-person evaluation and biopsy, as well as investigating the effectiveness of teledermatology for melanocytic lesions, which frequently are removed from analysis in large-scale teledermatology studies.

Although teledermatology has substantial clinical utility and may serve as a great resource for specific populations, including geriatric patients and those who are immunocompromised, it is important to recognize notable limitations. Specifically, brief history and image review should not serve as replacements for a face-to-face visit with physical examination in cases where the diagnosis remains uncertain or when high-risk skin malignancies are suspected or included in the differential. Certain aggressive cutaneous malignancies such as Merkel cell carcinoma may appear as less aggressive via teledermatology due to restrictions of technology.

Conclusion

Teledermatology has had a major impact on the way health care is delivered to patients and may increase access to care, reducing unnecessary in-person visits and decreasing the number of in-person visit no-shows. With the appropriate use of a brief clinical history and image review, teledermatology can be effective to evaluate specific lesions of concern. We report 3 unique cases identified during a 1-month period at a large Midwestern medical center. These cases serve as important examples of the application of teledermatology in reducing the time to diagnosis of aggressive skin malignancies. Further research on the clinical utility of teledermatology is warranted.

Acknowledgments—The authors thank the additional providers from the University of Wisconsin and William S. Middleton Memorial Veterans Hospital (both in Madison, Wisconsin) involved in the medical care of the patients included in this case series.

Sunscreen is a cornerstone of skin cancer prevention. The first commercial sunscreen was developed nearly 100 years ago,¹ yet questions and concerns about the safety of these essential topical photoprotective agents continue to occupy our minds. This article serves as an update on some of the big sunscreen questions, as informed by the available evidence.

Are sunscreens safe?

The story of sunscreen regulation in the United States is long and dry. The major pain point is that sunscreens are regulated by the US Food and Drug Administration (FDA) as over-the-counter drugs rather than cosmetics (as in Europe).² Regulatory hurdles created a situation wherein no new active sunscreen ingredient has been approved by the FDA since 1999, except ecamsule for use in one product line. There is hope that changes enacted under the CARES Act will streamline and expedite the sunscreen approval process in the future.³

Amid the ongoing regulatory slog, the FDA became interested in learning more about sunscreen safety. Specifically, they sought to determine the GRASE (generally regarded as safe and effective) status of the active ingredients in sunscreens. In 2019, only the inorganic (physical/mineral) UV filters zinc oxide and titanium dioxide were considered GRASE.⁴ Trolamine salicylate and para-aminobenzoic acid were not GRASE, but they currently are not used in sunscreens in the United States. For all the remaining organic (chemical) filters, additional safety data were required to establish GRASE status.⁴ In 2024, the situation remains largely unchanged. Industry is working with the FDA on testing requirements.⁵

Why the focus on safety? After all, sunscreens have been used widely for decades without any major safety signals; their only well-established adverse effects are contact dermatitis and staining of clothing.⁶ Although preclinical studies raised concerns that chemical sunscreens could be associated with endocrine, reproductive, and neurologic toxicities, to date there are no high-quality human studies demonstrating negative effects.^7,8

However, exposure patterns have evolved. Sunscreen is recommended to be applied (and reapplied) daily. Also, chemical UV filters are used in many nonsunscreen products such as cosmetics, shampoos, fragrances, and plastics. In the United States, exposure to chemical sunscreens is ubiquitous; according to data from the National Health and Nutrition Examination Survey 2003-2004, oxybenzone was detected in 97% of more than 2500 urine samples, implying systemic absorption but not harm.⁹

The FDA confirmed the implication of systemic absorption via 2 maximal usage trials published in 2019 and 2020.^10,11 In both studies, several chemical sunscreens were applied at the recommended density of 2 mg/cm² to 75% of the body surface area multiple times over 4 days. For all tested organic UV filters, blood levels exceeded the predetermined FDA cutoff (0.5 ng/mL), even after one application.^10,11 What’s the takeaway? Simply that the FDA now requires additional safety data for chemical sunscreen filters⁵; the findings in no way imply any associated harm. Two potential mitigating factors are that no one applies sunscreen at 2 mg/cm², and the FDA’s blood level cutoff was a general estimate not specific to sunscreens.^4,12

Nevertheless, a good long-term safety record for sunscreens does not negate the need for enhanced safety data when there is clear evidence of systemic absorption. In the meantime, concerned patients should be counseled that the physical/mineral sunscreens containing zinc oxide and titanium dioxide are considered GRASE by the FDA; even in nanoparticle form, they generally have not been found to penetrate beneath the stratum corneum.^7,13

 

 

Does sunscreen cause frontal fibrosing alopecia?

Dermatologists are confronting the conundrum of rising cases of frontal fibrosing alopecia (FFA). Several theories on the pathogenesis of this idiopathic scarring alopecia have been raised, one of which involves increased use of sunscreen. Proposed explanations for sunscreen’s role in FFA include a lichenoid reaction inducing hair follicle autoimmunity through an unclear mechanism; a T cell–mediated allergic reaction, which is unlikely according to contact dermatitis experts¹⁴; reactive oxygen species production by titanium nanoparticles, yet titanium has been detected in hair follicles of both patients with FFA and controls¹⁵; and endocrine disruption following systemic absorption, which has not been supported by any high-quality human studies.⁷

An association between facial sunscreen use and FFA has been reported in case-control studies¹⁶; however, they have been criticized due to methodologic issues and biases, and they provide no evidence of causality.^17,18 The jury remains out on the controversial association between sunscreen and FFA, with a need for more convincing data.

Does sunscreen impact coral reef health?

Coral reefs—crucial sources of aquatic biodiversity—are under attack from several different directions including climate change and pollution. As much as 14,000 tons of sunscreen enter coral reefs each year, and chemical sunscreen filters are detectable in waterways throughout the world—even in the Arctic.^19,20 Thus, sunscreen has come under scrutiny as a potential environmental threat, particularly with coral bleaching.

Bleaching is a process in which corals exposed to an environmental stressor expel their symbiotic photosynthetic algae and turn white; if conditions fail to improve, the corals are vulnerable to death. In a highly cited 2016 study, coral larvae exposed to oxybenzone in artificial laboratory conditions displayed concentration-dependent mortality and decreased chlorophyll fluorescence, which suggested bleaching.¹⁹ These findings influenced legislation in Hawaii and other localities banning sunscreens containing oxybenzone. Problematically, the study has been criticized for acutely exposing the most susceptible coral life-forms to unrealistic oxybenzone concentrations; more broadly, there is no standardized approach to coral toxicity testing.²¹

The bigger picture (and elephant in the room) is that the primary cause of coral bleaching is undoubtedly climate change/ocean warming.⁷ More recent studies suggest that oxybenzone probably adds insult to injury for corals already debilitated by ocean warming.^22,23

It has been posited that a narrow focus on sunscreens detracts attention from the climate issue.²⁴ Individuals can take a number of actions to reduce their carbon footprint in an effort to preserve our environment, specifically coral reefs.²⁵ Concerned patients should be counseled to use sunscreens containing the physical/mineral UV filters zinc oxide and titanium dioxide, which are unlikely to contribute to coral bleaching as commercially formulated.⁷

Ongoing Questions

A lot of unknowns about sunscreen safety remain, and much hubbub has been made over studies that often are preliminary at best. At the time of this writing, absent a crystal ball, this author continues to wear chemical sunscreens; spends a lot more time worrying about their carbon footprint than what type of sunscreen to use at the beach; and believes the association of FFA with sunscreen is unlikely to be causal. Hopefully much-needed rigorous evidence will guide our future approach to sunscreen formulation and use.

Sunscreen is a cornerstone of skin cancer prevention. The first commercial sunscreen was developed nearly 100 years ago,¹ yet questions and concerns about the safety of these essential topical photoprotective agents continue to occupy our minds. This article serves as an update on some of the big sunscreen questions, as informed by the available evidence.

Are sunscreens safe?

The story of sunscreen regulation in the United States is long and dry. The major pain point is that sunscreens are regulated by the US Food and Drug Administration (FDA) as over-the-counter drugs rather than cosmetics (as in Europe).² Regulatory hurdles created a situation wherein no new active sunscreen ingredient has been approved by the FDA since 1999, except ecamsule for use in one product line. There is hope that changes enacted under the CARES Act will streamline and expedite the sunscreen approval process in the future.³

Amid the ongoing regulatory slog, the FDA became interested in learning more about sunscreen safety. Specifically, they sought to determine the GRASE (generally regarded as safe and effective) status of the active ingredients in sunscreens. In 2019, only the inorganic (physical/mineral) UV filters zinc oxide and titanium dioxide were considered GRASE.⁴ Trolamine salicylate and para-aminobenzoic acid were not GRASE, but they currently are not used in sunscreens in the United States. For all the remaining organic (chemical) filters, additional safety data were required to establish GRASE status.⁴ In 2024, the situation remains largely unchanged. Industry is working with the FDA on testing requirements.⁵

Why the focus on safety? After all, sunscreens have been used widely for decades without any major safety signals; their only well-established adverse effects are contact dermatitis and staining of clothing.⁶ Although preclinical studies raised concerns that chemical sunscreens could be associated with endocrine, reproductive, and neurologic toxicities, to date there are no high-quality human studies demonstrating negative effects.^7,8

However, exposure patterns have evolved. Sunscreen is recommended to be applied (and reapplied) daily. Also, chemical UV filters are used in many nonsunscreen products such as cosmetics, shampoos, fragrances, and plastics. In the United States, exposure to chemical sunscreens is ubiquitous; according to data from the National Health and Nutrition Examination Survey 2003-2004, oxybenzone was detected in 97% of more than 2500 urine samples, implying systemic absorption but not harm.⁹

The FDA confirmed the implication of systemic absorption via 2 maximal usage trials published in 2019 and 2020.^10,11 In both studies, several chemical sunscreens were applied at the recommended density of 2 mg/cm² to 75% of the body surface area multiple times over 4 days. For all tested organic UV filters, blood levels exceeded the predetermined FDA cutoff (0.5 ng/mL), even after one application.^10,11 What’s the takeaway? Simply that the FDA now requires additional safety data for chemical sunscreen filters⁵; the findings in no way imply any associated harm. Two potential mitigating factors are that no one applies sunscreen at 2 mg/cm², and the FDA’s blood level cutoff was a general estimate not specific to sunscreens.^4,12

Nevertheless, a good long-term safety record for sunscreens does not negate the need for enhanced safety data when there is clear evidence of systemic absorption. In the meantime, concerned patients should be counseled that the physical/mineral sunscreens containing zinc oxide and titanium dioxide are considered GRASE by the FDA; even in nanoparticle form, they generally have not been found to penetrate beneath the stratum corneum.^7,13

 

 

Does sunscreen cause frontal fibrosing alopecia?

Dermatologists are confronting the conundrum of rising cases of frontal fibrosing alopecia (FFA). Several theories on the pathogenesis of this idiopathic scarring alopecia have been raised, one of which involves increased use of sunscreen. Proposed explanations for sunscreen’s role in FFA include a lichenoid reaction inducing hair follicle autoimmunity through an unclear mechanism; a T cell–mediated allergic reaction, which is unlikely according to contact dermatitis experts¹⁴; reactive oxygen species production by titanium nanoparticles, yet titanium has been detected in hair follicles of both patients with FFA and controls¹⁵; and endocrine disruption following systemic absorption, which has not been supported by any high-quality human studies.⁷

An association between facial sunscreen use and FFA has been reported in case-control studies¹⁶; however, they have been criticized due to methodologic issues and biases, and they provide no evidence of causality.^17,18 The jury remains out on the controversial association between sunscreen and FFA, with a need for more convincing data.

Does sunscreen impact coral reef health?

Coral reefs—crucial sources of aquatic biodiversity—are under attack from several different directions including climate change and pollution. As much as 14,000 tons of sunscreen enter coral reefs each year, and chemical sunscreen filters are detectable in waterways throughout the world—even in the Arctic.^19,20 Thus, sunscreen has come under scrutiny as a potential environmental threat, particularly with coral bleaching.

Bleaching is a process in which corals exposed to an environmental stressor expel their symbiotic photosynthetic algae and turn white; if conditions fail to improve, the corals are vulnerable to death. In a highly cited 2016 study, coral larvae exposed to oxybenzone in artificial laboratory conditions displayed concentration-dependent mortality and decreased chlorophyll fluorescence, which suggested bleaching.¹⁹ These findings influenced legislation in Hawaii and other localities banning sunscreens containing oxybenzone. Problematically, the study has been criticized for acutely exposing the most susceptible coral life-forms to unrealistic oxybenzone concentrations; more broadly, there is no standardized approach to coral toxicity testing.²¹

The bigger picture (and elephant in the room) is that the primary cause of coral bleaching is undoubtedly climate change/ocean warming.⁷ More recent studies suggest that oxybenzone probably adds insult to injury for corals already debilitated by ocean warming.^22,23

It has been posited that a narrow focus on sunscreens detracts attention from the climate issue.²⁴ Individuals can take a number of actions to reduce their carbon footprint in an effort to preserve our environment, specifically coral reefs.²⁵ Concerned patients should be counseled to use sunscreens containing the physical/mineral UV filters zinc oxide and titanium dioxide, which are unlikely to contribute to coral bleaching as commercially formulated.⁷

Ongoing Questions

A lot of unknowns about sunscreen safety remain, and much hubbub has been made over studies that often are preliminary at best. At the time of this writing, absent a crystal ball, this author continues to wear chemical sunscreens; spends a lot more time worrying about their carbon footprint than what type of sunscreen to use at the beach; and believes the association of FFA with sunscreen is unlikely to be causal. Hopefully much-needed rigorous evidence will guide our future approach to sunscreen formulation and use.

Sunscreen is a cornerstone of skin cancer prevention. The first commercial sunscreen was developed nearly 100 years ago,¹ yet questions and concerns about the safety of these essential topical photoprotective agents continue to occupy our minds. This article serves as an update on some of the big sunscreen questions, as informed by the available evidence.

Are sunscreens safe?

The story of sunscreen regulation in the United States is long and dry. The major pain point is that sunscreens are regulated by the US Food and Drug Administration (FDA) as over-the-counter drugs rather than cosmetics (as in Europe).² Regulatory hurdles created a situation wherein no new active sunscreen ingredient has been approved by the FDA since 1999, except ecamsule for use in one product line. There is hope that changes enacted under the CARES Act will streamline and expedite the sunscreen approval process in the future.³

Amid the ongoing regulatory slog, the FDA became interested in learning more about sunscreen safety. Specifically, they sought to determine the GRASE (generally regarded as safe and effective) status of the active ingredients in sunscreens. In 2019, only the inorganic (physical/mineral) UV filters zinc oxide and titanium dioxide were considered GRASE.⁴ Trolamine salicylate and para-aminobenzoic acid were not GRASE, but they currently are not used in sunscreens in the United States. For all the remaining organic (chemical) filters, additional safety data were required to establish GRASE status.⁴ In 2024, the situation remains largely unchanged. Industry is working with the FDA on testing requirements.⁵

Why the focus on safety? After all, sunscreens have been used widely for decades without any major safety signals; their only well-established adverse effects are contact dermatitis and staining of clothing.⁶ Although preclinical studies raised concerns that chemical sunscreens could be associated with endocrine, reproductive, and neurologic toxicities, to date there are no high-quality human studies demonstrating negative effects.^7,8

However, exposure patterns have evolved. Sunscreen is recommended to be applied (and reapplied) daily. Also, chemical UV filters are used in many nonsunscreen products such as cosmetics, shampoos, fragrances, and plastics. In the United States, exposure to chemical sunscreens is ubiquitous; according to data from the National Health and Nutrition Examination Survey 2003-2004, oxybenzone was detected in 97% of more than 2500 urine samples, implying systemic absorption but not harm.⁹

The FDA confirmed the implication of systemic absorption via 2 maximal usage trials published in 2019 and 2020.^10,11 In both studies, several chemical sunscreens were applied at the recommended density of 2 mg/cm² to 75% of the body surface area multiple times over 4 days. For all tested organic UV filters, blood levels exceeded the predetermined FDA cutoff (0.5 ng/mL), even after one application.^10,11 What’s the takeaway? Simply that the FDA now requires additional safety data for chemical sunscreen filters⁵; the findings in no way imply any associated harm. Two potential mitigating factors are that no one applies sunscreen at 2 mg/cm², and the FDA’s blood level cutoff was a general estimate not specific to sunscreens.^4,12

Nevertheless, a good long-term safety record for sunscreens does not negate the need for enhanced safety data when there is clear evidence of systemic absorption. In the meantime, concerned patients should be counseled that the physical/mineral sunscreens containing zinc oxide and titanium dioxide are considered GRASE by the FDA; even in nanoparticle form, they generally have not been found to penetrate beneath the stratum corneum.^7,13

 

 

Does sunscreen cause frontal fibrosing alopecia?

Dermatologists are confronting the conundrum of rising cases of frontal fibrosing alopecia (FFA). Several theories on the pathogenesis of this idiopathic scarring alopecia have been raised, one of which involves increased use of sunscreen. Proposed explanations for sunscreen’s role in FFA include a lichenoid reaction inducing hair follicle autoimmunity through an unclear mechanism; a T cell–mediated allergic reaction, which is unlikely according to contact dermatitis experts¹⁴; reactive oxygen species production by titanium nanoparticles, yet titanium has been detected in hair follicles of both patients with FFA and controls¹⁵; and endocrine disruption following systemic absorption, which has not been supported by any high-quality human studies.⁷

An association between facial sunscreen use and FFA has been reported in case-control studies¹⁶; however, they have been criticized due to methodologic issues and biases, and they provide no evidence of causality.^17,18 The jury remains out on the controversial association between sunscreen and FFA, with a need for more convincing data.

Does sunscreen impact coral reef health?

Coral reefs—crucial sources of aquatic biodiversity—are under attack from several different directions including climate change and pollution. As much as 14,000 tons of sunscreen enter coral reefs each year, and chemical sunscreen filters are detectable in waterways throughout the world—even in the Arctic.^19,20 Thus, sunscreen has come under scrutiny as a potential environmental threat, particularly with coral bleaching.

Bleaching is a process in which corals exposed to an environmental stressor expel their symbiotic photosynthetic algae and turn white; if conditions fail to improve, the corals are vulnerable to death. In a highly cited 2016 study, coral larvae exposed to oxybenzone in artificial laboratory conditions displayed concentration-dependent mortality and decreased chlorophyll fluorescence, which suggested bleaching.¹⁹ These findings influenced legislation in Hawaii and other localities banning sunscreens containing oxybenzone. Problematically, the study has been criticized for acutely exposing the most susceptible coral life-forms to unrealistic oxybenzone concentrations; more broadly, there is no standardized approach to coral toxicity testing.²¹

The bigger picture (and elephant in the room) is that the primary cause of coral bleaching is undoubtedly climate change/ocean warming.⁷ More recent studies suggest that oxybenzone probably adds insult to injury for corals already debilitated by ocean warming.^22,23

It has been posited that a narrow focus on sunscreens detracts attention from the climate issue.²⁴ Individuals can take a number of actions to reduce their carbon footprint in an effort to preserve our environment, specifically coral reefs.²⁵ Concerned patients should be counseled to use sunscreens containing the physical/mineral UV filters zinc oxide and titanium dioxide, which are unlikely to contribute to coral bleaching as commercially formulated.⁷

Ongoing Questions

A lot of unknowns about sunscreen safety remain, and much hubbub has been made over studies that often are preliminary at best. At the time of this writing, absent a crystal ball, this author continues to wear chemical sunscreens; spends a lot more time worrying about their carbon footprint than what type of sunscreen to use at the beach; and believes the association of FFA with sunscreen is unlikely to be causal. Hopefully much-needed rigorous evidence will guide our future approach to sunscreen formulation and use.

SAN DIEGO — Approximately 10 years ago in France, high throughput screening in a series of cases suggested that vaccine-derived rubella virus was the surprising cause of persistent cutaneous granulomas, but an update at the annual meeting of the American Academy of Dermatology suggests this phenomenon is not as rare as once supposed.

Based on accumulating evidence, the Centers for Disease Control and Prevention (CDC) through collaborations with others also recognized this in pediatric patients with inborn errors of immunity, and it is now appropriate for clinicians to consider this etiology when no other infectious agents can be identified, according to Karolyn A. Wanat, MD, professor of dermatology, Medical College of Wisconsin, Milwaukee, who spoke about rubella as a trigger in granulomatous disease at the meeting. “This is a huge evolving area of interest,” said Dr. Wanat, who has been the first author or coauthor on several published papers, including a review article published earlier this year.

In the earliest cases, including those reported in 2014, the cutaneous granulomas presumed to be causally related to vaccine-derived rubella virus were found only in those with a primary immunodeficiency. This is no longer the case. In a collaboration among US clinics, granulomas that had persisted for years in immunocompetent adults were identified, according to Dr. Wanat, the first author of a report on these findings in four adults in 2022. In addition, it now appears that wild-type rubella virus, like vaccine-derived rubella virus, can be the source of the antigenic response that underlies the development of rubella-associated cutaneous granulomas.

The phenotype of these granulomas is comparable to granulomas associated with other infectious agents. On dermatopathology, these commonly feature a robust granulomatous inflammation with multinucleated giant cells and lymphocytic infiltrate. Necrosis and fibrosis are also common.

“These are the types of granulomas that we would be thinking infection. If tissue cultures are negative, we would probably repeat them,” she said, suggesting that suspicion of an infectious etiology would probably remain high even after multiple negative tests.

Of the cases accruing in the United States and elsewhere, most but not all have been linked to inborn errors of immunity. In a 2020 CDC review, the risk of granulomas caused by compromised immunity, such as defects in T cell function, was estimated to be in the range of 0.6% to 2.5%, Dr. Wanat said.

It is now known that primary immunodeficiency is not a prerequisite, but this should not change the perception that the rubella vaccine, which was introduced in 1979, is effective and safe, according to Dr. Wanat. The vaccine is associated with few serious adverse events and is so effective that rubella was eliminated from the United States in 2004 and from the Americas in 2015.

This makes cases of granuloma associated with wild-type rubella virus surprising, but they appear to be exceedingly rare. Whether caused by vaccine exposure or another source, the mechanism of latent development of cutaneous granulomas is consistent with other infectious sources, and is not well understood.

“Rubella is a sneaky virus that can persist in some immunoprivileged sites indefinitely,” Dr. Wanat said. These sites include the eyes, joints, and placenta.

Many initial cases of rubella-associated granulomas occurred on the arms, presumably where the vaccine was administered, despite long intervals between exposure and lesion growth. This interval is often measured in years.

With more cases, it is now understood that involvement of other organs does occur even if the skin is the most common site of antigenic response in patients with immunodeficiency. The liver and lymph nodes represent other tissues that have been affected. Even lesions in the brain have been seen on autopsy.

Based on the benefit-to-risk ratio of a highly effective and successful vaccine, however, the association with a risk of granulomas “should not raise questions” about the value of the vaccine itself, Dr. Wanat noted.

“The proportion of patients who develop these granulomas is very, very low. Yet, the vaccine provides life-long immunity,” she said.

The discovery of granulomas associated with wild type rubella infection was “shocking” based on the supposition that the rubella virus had been eliminated, but this is just one of the unexpected discoveries as the still-evolving science has traced the story of rubella-associated granulomas over the past 10 years.

Cases now include children and adults through advanced ages.

Shedding of the virus and risk of infection to others has been studied but so far, the risk — if it exists — is very low. The evidence includes the many patients who have lived with the granulomas for years, even decades, without any known spread to others.

As for ongoing work in this area, Dr. Wanat said that a histopathological case definition for rubella-associated granulomas is being developed, and she and other investigators are actively seeking new cases to better characterize the disease.

So far, optimal treatment is not well defined. A number of strategies have had limited success or are considered impractical for routine use. One example is a stem cell transplant. In a case Dr. Wanat cited, complete resolution of the skin lesions was achieved with a transplant.

“I am not suggesting that those with localized disease in the skin should undergo a transplant, but it does support the role of the immune system and the potential for a reboot to clear the skin,” she said.

Other therapies associated with benefit in at least some patients include tumor necrosis factor (TNF) inhibitors with dapsone and ribavirin. The risk of adverse events for the latter might again limit its use, Dr. Wanat said.

With awareness, the number of granulomas found to be associated with rubella virus is expected to grow. Dr. Wanat speculated that those areas of the country that not yet have documented a case will do so over time. For idiopathic cases of cutaneous granulomas, rubella should be kept in mind, she said.

Characterizing rubella-associated cutaneous granulomas as “a public health concern,” Dr. Wanat urged clinicians to consider this etiology in lesions that match the phenotype, particularly when other more common infectious agents cannot be identified.

Asked for his perspective, Jeffrey P. North, MD, managing director of the UCSF Dermatopathology, and professor of dermatology and pathology at the University of California, San Francisco, agreed that rubella should be considered as a source of granulomas with a suspected infectious etiology when a pathogen cannot be found.

“It is likely much more common than we know as it has only been recently described and testing for it is limited. I suspected there are a lot of undiagnosed patients suffering from this disease,” Dr. North said in an interview.

“One of the important points for clinicians to consider is that while this has been reported mostly in patients with some form of immunodeficiency, there have also been patients reported to have this condition with no immunodeficiency,” he added. Even though the association between rubella and granulomas was made 10 years ago, awareness is only now spreading, which means the frequency with which rubella leads to granulomas remains uncertain.

“I think we will start to get a better idea of how common this is as more people learn about and testing for it expands,” Dr. North said.

Dr. Wanat reports no potential conflicts of interest. Dr. North reports financial relationships with AdviNow and Kiniksa Pharmaceuticals.

SAN DIEGO — Approximately 10 years ago in France, high throughput screening in a series of cases suggested that vaccine-derived rubella virus was the surprising cause of persistent cutaneous granulomas, but an update at the annual meeting of the American Academy of Dermatology suggests this phenomenon is not as rare as once supposed.

Based on accumulating evidence, the Centers for Disease Control and Prevention (CDC) through collaborations with others also recognized this in pediatric patients with inborn errors of immunity, and it is now appropriate for clinicians to consider this etiology when no other infectious agents can be identified, according to Karolyn A. Wanat, MD, professor of dermatology, Medical College of Wisconsin, Milwaukee, who spoke about rubella as a trigger in granulomatous disease at the meeting. “This is a huge evolving area of interest,” said Dr. Wanat, who has been the first author or coauthor on several published papers, including a review article published earlier this year.

In the earliest cases, including those reported in 2014, the cutaneous granulomas presumed to be causally related to vaccine-derived rubella virus were found only in those with a primary immunodeficiency. This is no longer the case. In a collaboration among US clinics, granulomas that had persisted for years in immunocompetent adults were identified, according to Dr. Wanat, the first author of a report on these findings in four adults in 2022. In addition, it now appears that wild-type rubella virus, like vaccine-derived rubella virus, can be the source of the antigenic response that underlies the development of rubella-associated cutaneous granulomas.

The phenotype of these granulomas is comparable to granulomas associated with other infectious agents. On dermatopathology, these commonly feature a robust granulomatous inflammation with multinucleated giant cells and lymphocytic infiltrate. Necrosis and fibrosis are also common.

“These are the types of granulomas that we would be thinking infection. If tissue cultures are negative, we would probably repeat them,” she said, suggesting that suspicion of an infectious etiology would probably remain high even after multiple negative tests.

Of the cases accruing in the United States and elsewhere, most but not all have been linked to inborn errors of immunity. In a 2020 CDC review, the risk of granulomas caused by compromised immunity, such as defects in T cell function, was estimated to be in the range of 0.6% to 2.5%, Dr. Wanat said.

It is now known that primary immunodeficiency is not a prerequisite, but this should not change the perception that the rubella vaccine, which was introduced in 1979, is effective and safe, according to Dr. Wanat. The vaccine is associated with few serious adverse events and is so effective that rubella was eliminated from the United States in 2004 and from the Americas in 2015.

This makes cases of granuloma associated with wild-type rubella virus surprising, but they appear to be exceedingly rare. Whether caused by vaccine exposure or another source, the mechanism of latent development of cutaneous granulomas is consistent with other infectious sources, and is not well understood.

“Rubella is a sneaky virus that can persist in some immunoprivileged sites indefinitely,” Dr. Wanat said. These sites include the eyes, joints, and placenta.

Many initial cases of rubella-associated granulomas occurred on the arms, presumably where the vaccine was administered, despite long intervals between exposure and lesion growth. This interval is often measured in years.

With more cases, it is now understood that involvement of other organs does occur even if the skin is the most common site of antigenic response in patients with immunodeficiency. The liver and lymph nodes represent other tissues that have been affected. Even lesions in the brain have been seen on autopsy.

Based on the benefit-to-risk ratio of a highly effective and successful vaccine, however, the association with a risk of granulomas “should not raise questions” about the value of the vaccine itself, Dr. Wanat noted.

“The proportion of patients who develop these granulomas is very, very low. Yet, the vaccine provides life-long immunity,” she said.

The discovery of granulomas associated with wild type rubella infection was “shocking” based on the supposition that the rubella virus had been eliminated, but this is just one of the unexpected discoveries as the still-evolving science has traced the story of rubella-associated granulomas over the past 10 years.

Cases now include children and adults through advanced ages.

Shedding of the virus and risk of infection to others has been studied but so far, the risk — if it exists — is very low. The evidence includes the many patients who have lived with the granulomas for years, even decades, without any known spread to others.

As for ongoing work in this area, Dr. Wanat said that a histopathological case definition for rubella-associated granulomas is being developed, and she and other investigators are actively seeking new cases to better characterize the disease.

So far, optimal treatment is not well defined. A number of strategies have had limited success or are considered impractical for routine use. One example is a stem cell transplant. In a case Dr. Wanat cited, complete resolution of the skin lesions was achieved with a transplant.

“I am not suggesting that those with localized disease in the skin should undergo a transplant, but it does support the role of the immune system and the potential for a reboot to clear the skin,” she said.

Other therapies associated with benefit in at least some patients include tumor necrosis factor (TNF) inhibitors with dapsone and ribavirin. The risk of adverse events for the latter might again limit its use, Dr. Wanat said.

With awareness, the number of granulomas found to be associated with rubella virus is expected to grow. Dr. Wanat speculated that those areas of the country that not yet have documented a case will do so over time. For idiopathic cases of cutaneous granulomas, rubella should be kept in mind, she said.

Characterizing rubella-associated cutaneous granulomas as “a public health concern,” Dr. Wanat urged clinicians to consider this etiology in lesions that match the phenotype, particularly when other more common infectious agents cannot be identified.

Asked for his perspective, Jeffrey P. North, MD, managing director of the UCSF Dermatopathology, and professor of dermatology and pathology at the University of California, San Francisco, agreed that rubella should be considered as a source of granulomas with a suspected infectious etiology when a pathogen cannot be found.

“It is likely much more common than we know as it has only been recently described and testing for it is limited. I suspected there are a lot of undiagnosed patients suffering from this disease,” Dr. North said in an interview.

“One of the important points for clinicians to consider is that while this has been reported mostly in patients with some form of immunodeficiency, there have also been patients reported to have this condition with no immunodeficiency,” he added. Even though the association between rubella and granulomas was made 10 years ago, awareness is only now spreading, which means the frequency with which rubella leads to granulomas remains uncertain.

“I think we will start to get a better idea of how common this is as more people learn about and testing for it expands,” Dr. North said.

Dr. Wanat reports no potential conflicts of interest. Dr. North reports financial relationships with AdviNow and Kiniksa Pharmaceuticals.

SAN DIEGO — Approximately 10 years ago in France, high throughput screening in a series of cases suggested that vaccine-derived rubella virus was the surprising cause of persistent cutaneous granulomas, but an update at the annual meeting of the American Academy of Dermatology suggests this phenomenon is not as rare as once supposed.

Based on accumulating evidence, the Centers for Disease Control and Prevention (CDC) through collaborations with others also recognized this in pediatric patients with inborn errors of immunity, and it is now appropriate for clinicians to consider this etiology when no other infectious agents can be identified, according to Karolyn A. Wanat, MD, professor of dermatology, Medical College of Wisconsin, Milwaukee, who spoke about rubella as a trigger in granulomatous disease at the meeting. “This is a huge evolving area of interest,” said Dr. Wanat, who has been the first author or coauthor on several published papers, including a review article published earlier this year.

In the earliest cases, including those reported in 2014, the cutaneous granulomas presumed to be causally related to vaccine-derived rubella virus were found only in those with a primary immunodeficiency. This is no longer the case. In a collaboration among US clinics, granulomas that had persisted for years in immunocompetent adults were identified, according to Dr. Wanat, the first author of a report on these findings in four adults in 2022. In addition, it now appears that wild-type rubella virus, like vaccine-derived rubella virus, can be the source of the antigenic response that underlies the development of rubella-associated cutaneous granulomas.

The phenotype of these granulomas is comparable to granulomas associated with other infectious agents. On dermatopathology, these commonly feature a robust granulomatous inflammation with multinucleated giant cells and lymphocytic infiltrate. Necrosis and fibrosis are also common.

“These are the types of granulomas that we would be thinking infection. If tissue cultures are negative, we would probably repeat them,” she said, suggesting that suspicion of an infectious etiology would probably remain high even after multiple negative tests.

Of the cases accruing in the United States and elsewhere, most but not all have been linked to inborn errors of immunity. In a 2020 CDC review, the risk of granulomas caused by compromised immunity, such as defects in T cell function, was estimated to be in the range of 0.6% to 2.5%, Dr. Wanat said.

It is now known that primary immunodeficiency is not a prerequisite, but this should not change the perception that the rubella vaccine, which was introduced in 1979, is effective and safe, according to Dr. Wanat. The vaccine is associated with few serious adverse events and is so effective that rubella was eliminated from the United States in 2004 and from the Americas in 2015.

This makes cases of granuloma associated with wild-type rubella virus surprising, but they appear to be exceedingly rare. Whether caused by vaccine exposure or another source, the mechanism of latent development of cutaneous granulomas is consistent with other infectious sources, and is not well understood.

“Rubella is a sneaky virus that can persist in some immunoprivileged sites indefinitely,” Dr. Wanat said. These sites include the eyes, joints, and placenta.

Many initial cases of rubella-associated granulomas occurred on the arms, presumably where the vaccine was administered, despite long intervals between exposure and lesion growth. This interval is often measured in years.

With more cases, it is now understood that involvement of other organs does occur even if the skin is the most common site of antigenic response in patients with immunodeficiency. The liver and lymph nodes represent other tissues that have been affected. Even lesions in the brain have been seen on autopsy.

Based on the benefit-to-risk ratio of a highly effective and successful vaccine, however, the association with a risk of granulomas “should not raise questions” about the value of the vaccine itself, Dr. Wanat noted.

“The proportion of patients who develop these granulomas is very, very low. Yet, the vaccine provides life-long immunity,” she said.

The discovery of granulomas associated with wild type rubella infection was “shocking” based on the supposition that the rubella virus had been eliminated, but this is just one of the unexpected discoveries as the still-evolving science has traced the story of rubella-associated granulomas over the past 10 years.

Cases now include children and adults through advanced ages.

Shedding of the virus and risk of infection to others has been studied but so far, the risk — if it exists — is very low. The evidence includes the many patients who have lived with the granulomas for years, even decades, without any known spread to others.

As for ongoing work in this area, Dr. Wanat said that a histopathological case definition for rubella-associated granulomas is being developed, and she and other investigators are actively seeking new cases to better characterize the disease.

So far, optimal treatment is not well defined. A number of strategies have had limited success or are considered impractical for routine use. One example is a stem cell transplant. In a case Dr. Wanat cited, complete resolution of the skin lesions was achieved with a transplant.

“I am not suggesting that those with localized disease in the skin should undergo a transplant, but it does support the role of the immune system and the potential for a reboot to clear the skin,” she said.

Other therapies associated with benefit in at least some patients include tumor necrosis factor (TNF) inhibitors with dapsone and ribavirin. The risk of adverse events for the latter might again limit its use, Dr. Wanat said.

With awareness, the number of granulomas found to be associated with rubella virus is expected to grow. Dr. Wanat speculated that those areas of the country that not yet have documented a case will do so over time. For idiopathic cases of cutaneous granulomas, rubella should be kept in mind, she said.

Characterizing rubella-associated cutaneous granulomas as “a public health concern,” Dr. Wanat urged clinicians to consider this etiology in lesions that match the phenotype, particularly when other more common infectious agents cannot be identified.

Asked for his perspective, Jeffrey P. North, MD, managing director of the UCSF Dermatopathology, and professor of dermatology and pathology at the University of California, San Francisco, agreed that rubella should be considered as a source of granulomas with a suspected infectious etiology when a pathogen cannot be found.

“It is likely much more common than we know as it has only been recently described and testing for it is limited. I suspected there are a lot of undiagnosed patients suffering from this disease,” Dr. North said in an interview.

“One of the important points for clinicians to consider is that while this has been reported mostly in patients with some form of immunodeficiency, there have also been patients reported to have this condition with no immunodeficiency,” he added. Even though the association between rubella and granulomas was made 10 years ago, awareness is only now spreading, which means the frequency with which rubella leads to granulomas remains uncertain.

“I think we will start to get a better idea of how common this is as more people learn about and testing for it expands,” Dr. North said.

Dr. Wanat reports no potential conflicts of interest. Dr. North reports financial relationships with AdviNow and Kiniksa Pharmaceuticals.

Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.

In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.

Morsa Images/DigitalVision/Getty Images

The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).

“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.

“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”

These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:

• Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
• Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
• Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
• The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.

Trying Locum Tenens Early in Career

According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.

In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.

Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).

“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”

A version of this article appeared on Medscape.com.

Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.

In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.

Morsa Images/DigitalVision/Getty Images

The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).

“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.

“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”

These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:

• Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
• Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
• Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
• The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.

Trying Locum Tenens Early in Career

According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.

In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.

Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).

“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”

A version of this article appeared on Medscape.com.

Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.

In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.

Morsa Images/DigitalVision/Getty Images

The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).

“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.

“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”

These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:

• Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
• Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
• Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
• The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.

Trying Locum Tenens Early in Career

According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.

In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.

Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).

“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”

A version of this article appeared on Medscape.com.

Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.

We’re not talking theory or hoped-for breakthroughs in the next decade. These technologies are already a reality for many doctors and expected to grow rapidly in the next 1-3 years.

Are you ready? Let’s find out.

1. Artificial Intelligence (AI) Medical Scribes

You may already be using this or, at the very least, have heard about it.

Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.

“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.

Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”

Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.

“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”

Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”

2. Three-Dimensional (3D) Printing

Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.

“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”

Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.

“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.

The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.

3. Drones

For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.

Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.

Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.

“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.

According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.

4. Portable Ultrasound

Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.

AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.

“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.

More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.

5. Virtual Reality (VR)

When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.

“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.

Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.

“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”

Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.

Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.

A version of this article appeared on Medscape.com.

Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.

We’re not talking theory or hoped-for breakthroughs in the next decade. These technologies are already a reality for many doctors and expected to grow rapidly in the next 1-3 years.

Are you ready? Let’s find out.

1. Artificial Intelligence (AI) Medical Scribes

You may already be using this or, at the very least, have heard about it.

Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.

“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.

Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”

Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.

“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”

Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”

2. Three-Dimensional (3D) Printing

Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.

“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”

Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.

“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.

The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.

3. Drones

For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.

Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.

Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.

“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.

According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.

4. Portable Ultrasound

Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.

AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.

“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.

More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.

5. Virtual Reality (VR)

When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.

“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.

Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.

“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”

Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.

Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.

A version of this article appeared on Medscape.com.

Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.

We’re not talking theory or hoped-for breakthroughs in the next decade. These technologies are already a reality for many doctors and expected to grow rapidly in the next 1-3 years.

Are you ready? Let’s find out.

1. Artificial Intelligence (AI) Medical Scribes

You may already be using this or, at the very least, have heard about it.

Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.

“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.

Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”

Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.

“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”

Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”

2. Three-Dimensional (3D) Printing

Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.

“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”

Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.

“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.

The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.

3. Drones

For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.

Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.

Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.

“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.

According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.

4. Portable Ultrasound

Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.

AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.

“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.

More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.

5. Virtual Reality (VR)

When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.

“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.

Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.

“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”

Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.

Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.

A version of this article appeared on Medscape.com.

In an extension study of patients with dystrophic epidermolysis bullosa (DEB) treated with the topical gene therapy beremagene geperpavec, wound closure rates and adverse events were similar to those seen in the phase 3 study and no new safety signals were identified.

The results were presented by Amy S. Paller, MD, during a late-breaking session at the annual meeting of the American Academy of Dermatology.

In May 2023, beremagene geperpavec, marketed as Vyjuvek (formerly known as B-VEC) was approved by the US Food and Drug Administration (FDA) for the treatment of wounds in patients 6 months of age and older with DEB, a rare genetic blistering disorder caused by COL7A1 gene variants. The therapy uses a nonreplicating herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure. It is designed to be used repetitively, to heal a single wound, or on more than one wound.

In the pivotal study of patients with DEB, the gene therapy, delivered in a topical gel, was administered once a week for 6 months to one wound and placebo was applied to another wound for each participant. The proportion of wounds treated with beremagene geperpavec that healed was significantly higher than among placebo-treated wounds at 3 and 6 months (68% vs. 23% at 3 months, P = .003) and 65% vs. 26% at 6 months (P = .012), with no serious adverse events related to treatment.

The prospective, open label, uncontrolled extension study included 24 patients from the phase 3 study and 23 treatment-naive patients from five US sites. Their mean age was 16 years (range, 6 months to 46 years).

Of the 47 patients, 29 (62%) were on treatment for more than 1 year (the longest was about 2 years), and the mean duration of treatment was 475 days; 5 patients withdrew from the study for reasons not related to treatment.

Their types of adverse events (AEs) were similar to those seen in the phase 3 study and were consistent with what would be expected in patients with DEB, said Dr. Paller, professor and chair of dermatology, Northwestern University, Chicago. One patient experienced two wound hemorrhages that were possibly related to treatment, but there were no treatment-related AEs, no deaths or treatment discontinuations because of an AE, and no serious AEs thought to be related to treatment.

Wounds that were evaluated in the phase 3 study showed “a high durability of closure with continued treatment,” according to Dr. Paller. There were enough data on 19 of the 24 patients who had been in the phase 3 trial to evaluate wound closure, defined as “complete wound closure based on comparison to the exact wound area selected at baseline” at the beginning of the phase 3 study.

In the extension study, wound closure rates were almost 90% at baseline, 84.2% at 3 months, 61.1% at 6 months, 82.4% at 9 months, and 62.5% at 12 months, which was comparable to the rates observed in the third (86.4%) and sixth (73.7%) months of the phase 3 study, Dr. Paller said.

Patient-reported outcomes indicated that quality of life and satisfaction with treatment were preserved with continued treatment.The extension study was terminated in July 2023, after FDA approval, when patients could be transitioned to the commercially available treatment.Dr. Paller disclosed being an investigator (funds to institution) for multiple pharmaceutical companies, including the manufacturer of beremagene geperpavec, Krystal Biotech, which funded the study.

In an extension study of patients with dystrophic epidermolysis bullosa (DEB) treated with the topical gene therapy beremagene geperpavec, wound closure rates and adverse events were similar to those seen in the phase 3 study and no new safety signals were identified.

The results were presented by Amy S. Paller, MD, during a late-breaking session at the annual meeting of the American Academy of Dermatology.

In May 2023, beremagene geperpavec, marketed as Vyjuvek (formerly known as B-VEC) was approved by the US Food and Drug Administration (FDA) for the treatment of wounds in patients 6 months of age and older with DEB, a rare genetic blistering disorder caused by COL7A1 gene variants. The therapy uses a nonreplicating herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure. It is designed to be used repetitively, to heal a single wound, or on more than one wound.

In the pivotal study of patients with DEB, the gene therapy, delivered in a topical gel, was administered once a week for 6 months to one wound and placebo was applied to another wound for each participant. The proportion of wounds treated with beremagene geperpavec that healed was significantly higher than among placebo-treated wounds at 3 and 6 months (68% vs. 23% at 3 months, P = .003) and 65% vs. 26% at 6 months (P = .012), with no serious adverse events related to treatment.

The prospective, open label, uncontrolled extension study included 24 patients from the phase 3 study and 23 treatment-naive patients from five US sites. Their mean age was 16 years (range, 6 months to 46 years).

Of the 47 patients, 29 (62%) were on treatment for more than 1 year (the longest was about 2 years), and the mean duration of treatment was 475 days; 5 patients withdrew from the study for reasons not related to treatment.

Their types of adverse events (AEs) were similar to those seen in the phase 3 study and were consistent with what would be expected in patients with DEB, said Dr. Paller, professor and chair of dermatology, Northwestern University, Chicago. One patient experienced two wound hemorrhages that were possibly related to treatment, but there were no treatment-related AEs, no deaths or treatment discontinuations because of an AE, and no serious AEs thought to be related to treatment.

Wounds that were evaluated in the phase 3 study showed “a high durability of closure with continued treatment,” according to Dr. Paller. There were enough data on 19 of the 24 patients who had been in the phase 3 trial to evaluate wound closure, defined as “complete wound closure based on comparison to the exact wound area selected at baseline” at the beginning of the phase 3 study.

In the extension study, wound closure rates were almost 90% at baseline, 84.2% at 3 months, 61.1% at 6 months, 82.4% at 9 months, and 62.5% at 12 months, which was comparable to the rates observed in the third (86.4%) and sixth (73.7%) months of the phase 3 study, Dr. Paller said.

Patient-reported outcomes indicated that quality of life and satisfaction with treatment were preserved with continued treatment.The extension study was terminated in July 2023, after FDA approval, when patients could be transitioned to the commercially available treatment.Dr. Paller disclosed being an investigator (funds to institution) for multiple pharmaceutical companies, including the manufacturer of beremagene geperpavec, Krystal Biotech, which funded the study.

In an extension study of patients with dystrophic epidermolysis bullosa (DEB) treated with the topical gene therapy beremagene geperpavec, wound closure rates and adverse events were similar to those seen in the phase 3 study and no new safety signals were identified.

The results were presented by Amy S. Paller, MD, during a late-breaking session at the annual meeting of the American Academy of Dermatology.

In May 2023, beremagene geperpavec, marketed as Vyjuvek (formerly known as B-VEC) was approved by the US Food and Drug Administration (FDA) for the treatment of wounds in patients 6 months of age and older with DEB, a rare genetic blistering disorder caused by COL7A1 gene variants. The therapy uses a nonreplicating herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure. It is designed to be used repetitively, to heal a single wound, or on more than one wound.

In the pivotal study of patients with DEB, the gene therapy, delivered in a topical gel, was administered once a week for 6 months to one wound and placebo was applied to another wound for each participant. The proportion of wounds treated with beremagene geperpavec that healed was significantly higher than among placebo-treated wounds at 3 and 6 months (68% vs. 23% at 3 months, P = .003) and 65% vs. 26% at 6 months (P = .012), with no serious adverse events related to treatment.

The prospective, open label, uncontrolled extension study included 24 patients from the phase 3 study and 23 treatment-naive patients from five US sites. Their mean age was 16 years (range, 6 months to 46 years).

Of the 47 patients, 29 (62%) were on treatment for more than 1 year (the longest was about 2 years), and the mean duration of treatment was 475 days; 5 patients withdrew from the study for reasons not related to treatment.

Their types of adverse events (AEs) were similar to those seen in the phase 3 study and were consistent with what would be expected in patients with DEB, said Dr. Paller, professor and chair of dermatology, Northwestern University, Chicago. One patient experienced two wound hemorrhages that were possibly related to treatment, but there were no treatment-related AEs, no deaths or treatment discontinuations because of an AE, and no serious AEs thought to be related to treatment.

Wounds that were evaluated in the phase 3 study showed “a high durability of closure with continued treatment,” according to Dr. Paller. There were enough data on 19 of the 24 patients who had been in the phase 3 trial to evaluate wound closure, defined as “complete wound closure based on comparison to the exact wound area selected at baseline” at the beginning of the phase 3 study.

In the extension study, wound closure rates were almost 90% at baseline, 84.2% at 3 months, 61.1% at 6 months, 82.4% at 9 months, and 62.5% at 12 months, which was comparable to the rates observed in the third (86.4%) and sixth (73.7%) months of the phase 3 study, Dr. Paller said.

Patient-reported outcomes indicated that quality of life and satisfaction with treatment were preserved with continued treatment.The extension study was terminated in July 2023, after FDA approval, when patients could be transitioned to the commercially available treatment.Dr. Paller disclosed being an investigator (funds to institution) for multiple pharmaceutical companies, including the manufacturer of beremagene geperpavec, Krystal Biotech, which funded the study.

A significant proportion of patients with moderate to severe plaque psoriasis achieved at least a 75% improvement in the Psoriasis Area and Severity Score (PASI 75) compared with those on placebo after 12 weeks of treatment with an investigational oral tyrosine kinase 2 (TYK2) inhibitor, in a phase 2 study presented during a late breaker presentation at the annual meeting of the American Academy of Dermatology.

ESK-001 is a highly-selective TYK2 inhibitor that “reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-alpha,” according to Alumis, the company developing ESK-001.

The STRIDE trial enrolled 228 adults (mean age, 48 years) with a mean PASI score of 17.8 at baseline, randomized to one of five doses of ESK-001, or placebo. Nearly 70% of those enrolled were men, 82.5% were White, nearly 6% were Asian, and about 4% were Black.

The proportion of patients achieving at least a PASI-75 at 12 weeks, the primary endpoint, ranged from 19.4% among those on the lower dose (10 mg a day) to 56.4% among those on 20 mg twice a day and those on 40 mg once a day, and 64.1% among those on 40 mg twice a day, the highest dose evaluated, compared with 0% of those on placebo.

In addition, 38.5% and 15.4% of those on the highest dose achieved a PASI 90 and PASI 100, respectively, at 12 weeks, according to results presented at the meeting by Kim A. Papp, MD.

Improvements in static Physician’s Global Assessment (sPGA) scores, a secondary endpoint, at 12 weeks were also observed; including 59% of those on the highest dose (40 mg twice a day) achieving an sPGA of 0/1 at 12 weeks, according to Dr. Papp, president of Probity Medical Research, in Waterloo, Ontario, and a study investigator.

Treatment was “generally safe and well tolerated” at all doses, and most treatment-emergent adverse events were “mild to moderate” and self-limited, he said.

The most frequent treatment emergent adverse events included headache and nasopharyngitis (also reported in the placebo group), and upper respiratory tract infections. No cases of treatment-related serious adverse events were reported, and there were no cases of MACE (major adverse cardiovascular events), serious infections, thromboses related to treatment, or lab or ECG findings of concern.

In an ongoing open label extension study, 165 patients on 40 mg once a day and those on 40 mg twice a day are continuing to be evaluated, and at week 16, have continued to show significant efficacy, with a favorable risk-benefit profile to date, according to Dr. Papp.

ESK-001 is also being evaluated in a phase 2b study of patients with systemic lupus erythematosus, and a phase 2 proof-of-concept study of patients with non-infectious uveitis, according to Alumis.

In addition to being an investigator for Alumis, Dr. Papp disclosed serving as an adviser, consultant, investigator, and/or speaker for multiple other pharmaceutical companies.

A significant proportion of patients with moderate to severe plaque psoriasis achieved at least a 75% improvement in the Psoriasis Area and Severity Score (PASI 75) compared with those on placebo after 12 weeks of treatment with an investigational oral tyrosine kinase 2 (TYK2) inhibitor, in a phase 2 study presented during a late breaker presentation at the annual meeting of the American Academy of Dermatology.

ESK-001 is a highly-selective TYK2 inhibitor that “reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-alpha,” according to Alumis, the company developing ESK-001.

The STRIDE trial enrolled 228 adults (mean age, 48 years) with a mean PASI score of 17.8 at baseline, randomized to one of five doses of ESK-001, or placebo. Nearly 70% of those enrolled were men, 82.5% were White, nearly 6% were Asian, and about 4% were Black.

The proportion of patients achieving at least a PASI-75 at 12 weeks, the primary endpoint, ranged from 19.4% among those on the lower dose (10 mg a day) to 56.4% among those on 20 mg twice a day and those on 40 mg once a day, and 64.1% among those on 40 mg twice a day, the highest dose evaluated, compared with 0% of those on placebo.

In addition, 38.5% and 15.4% of those on the highest dose achieved a PASI 90 and PASI 100, respectively, at 12 weeks, according to results presented at the meeting by Kim A. Papp, MD.

Improvements in static Physician’s Global Assessment (sPGA) scores, a secondary endpoint, at 12 weeks were also observed; including 59% of those on the highest dose (40 mg twice a day) achieving an sPGA of 0/1 at 12 weeks, according to Dr. Papp, president of Probity Medical Research, in Waterloo, Ontario, and a study investigator.

Treatment was “generally safe and well tolerated” at all doses, and most treatment-emergent adverse events were “mild to moderate” and self-limited, he said.

The most frequent treatment emergent adverse events included headache and nasopharyngitis (also reported in the placebo group), and upper respiratory tract infections. No cases of treatment-related serious adverse events were reported, and there were no cases of MACE (major adverse cardiovascular events), serious infections, thromboses related to treatment, or lab or ECG findings of concern.

In an ongoing open label extension study, 165 patients on 40 mg once a day and those on 40 mg twice a day are continuing to be evaluated, and at week 16, have continued to show significant efficacy, with a favorable risk-benefit profile to date, according to Dr. Papp.

ESK-001 is also being evaluated in a phase 2b study of patients with systemic lupus erythematosus, and a phase 2 proof-of-concept study of patients with non-infectious uveitis, according to Alumis.

In addition to being an investigator for Alumis, Dr. Papp disclosed serving as an adviser, consultant, investigator, and/or speaker for multiple other pharmaceutical companies.

A significant proportion of patients with moderate to severe plaque psoriasis achieved at least a 75% improvement in the Psoriasis Area and Severity Score (PASI 75) compared with those on placebo after 12 weeks of treatment with an investigational oral tyrosine kinase 2 (TYK2) inhibitor, in a phase 2 study presented during a late breaker presentation at the annual meeting of the American Academy of Dermatology.

ESK-001 is a highly-selective TYK2 inhibitor that “reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-alpha,” according to Alumis, the company developing ESK-001.

The STRIDE trial enrolled 228 adults (mean age, 48 years) with a mean PASI score of 17.8 at baseline, randomized to one of five doses of ESK-001, or placebo. Nearly 70% of those enrolled were men, 82.5% were White, nearly 6% were Asian, and about 4% were Black.

The proportion of patients achieving at least a PASI-75 at 12 weeks, the primary endpoint, ranged from 19.4% among those on the lower dose (10 mg a day) to 56.4% among those on 20 mg twice a day and those on 40 mg once a day, and 64.1% among those on 40 mg twice a day, the highest dose evaluated, compared with 0% of those on placebo.

In addition, 38.5% and 15.4% of those on the highest dose achieved a PASI 90 and PASI 100, respectively, at 12 weeks, according to results presented at the meeting by Kim A. Papp, MD.

Improvements in static Physician’s Global Assessment (sPGA) scores, a secondary endpoint, at 12 weeks were also observed; including 59% of those on the highest dose (40 mg twice a day) achieving an sPGA of 0/1 at 12 weeks, according to Dr. Papp, president of Probity Medical Research, in Waterloo, Ontario, and a study investigator.

Treatment was “generally safe and well tolerated” at all doses, and most treatment-emergent adverse events were “mild to moderate” and self-limited, he said.

The most frequent treatment emergent adverse events included headache and nasopharyngitis (also reported in the placebo group), and upper respiratory tract infections. No cases of treatment-related serious adverse events were reported, and there were no cases of MACE (major adverse cardiovascular events), serious infections, thromboses related to treatment, or lab or ECG findings of concern.

In an ongoing open label extension study, 165 patients on 40 mg once a day and those on 40 mg twice a day are continuing to be evaluated, and at week 16, have continued to show significant efficacy, with a favorable risk-benefit profile to date, according to Dr. Papp.

ESK-001 is also being evaluated in a phase 2b study of patients with systemic lupus erythematosus, and a phase 2 proof-of-concept study of patients with non-infectious uveitis, according to Alumis.

In addition to being an investigator for Alumis, Dr. Papp disclosed serving as an adviser, consultant, investigator, and/or speaker for multiple other pharmaceutical companies.

The Food and Drug Administration (FDA) has issued a complete response letter regarding the Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), which is under review for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), requesting more information from the manufacturer.

Pz-cel, which comprises autologous, COL7A1 gene–corrected epidermal sheets, is being evaluated for its ability to enable normal type VII collagen expression in a patient’s skin cells and to facilitate wound healing and pain reduction in wounds in patients with RDEB after a one-time application procedure. The cause of RDEB is a defect in the COL7A1 gene that “results in the inability to produce type VII collagen,” a press release from the manufacturer noted.

On April 22, 2024, the manufacturer Abeona Therapeutics announced that following a meeting with the FDA in March and in a subsequent request for information, the agency requires additional information to satisfy certain Chemistry Manufacturing and Controls requirements before the BLA for pz-cel can be approved. According to a press release from the company, the information pertains to validation requirements for certain manufacturing and release testing methods, including some that were observed during the FDA’s pre-licensing inspection.

The complete response letter did not identify any issues related to the clinical efficacy or safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support approval, according to the company.

The company anticipates completing the BLA resubmission in the third quarter of 2024. The application is supported by clinical efficacy and safety data from the pivotal phase 3 VIITAL study and a phase 1/2a study in patients with RDEB.

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

The Food and Drug Administration (FDA) has issued a complete response letter regarding the Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), which is under review for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), requesting more information from the manufacturer.

Pz-cel, which comprises autologous, COL7A1 gene–corrected epidermal sheets, is being evaluated for its ability to enable normal type VII collagen expression in a patient’s skin cells and to facilitate wound healing and pain reduction in wounds in patients with RDEB after a one-time application procedure. The cause of RDEB is a defect in the COL7A1 gene that “results in the inability to produce type VII collagen,” a press release from the manufacturer noted.

On April 22, 2024, the manufacturer Abeona Therapeutics announced that following a meeting with the FDA in March and in a subsequent request for information, the agency requires additional information to satisfy certain Chemistry Manufacturing and Controls requirements before the BLA for pz-cel can be approved. According to a press release from the company, the information pertains to validation requirements for certain manufacturing and release testing methods, including some that were observed during the FDA’s pre-licensing inspection.

The complete response letter did not identify any issues related to the clinical efficacy or safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support approval, according to the company.

The company anticipates completing the BLA resubmission in the third quarter of 2024. The application is supported by clinical efficacy and safety data from the pivotal phase 3 VIITAL study and a phase 1/2a study in patients with RDEB.

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

The Food and Drug Administration (FDA) has issued a complete response letter regarding the Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), which is under review for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), requesting more information from the manufacturer.

Pz-cel, which comprises autologous, COL7A1 gene–corrected epidermal sheets, is being evaluated for its ability to enable normal type VII collagen expression in a patient’s skin cells and to facilitate wound healing and pain reduction in wounds in patients with RDEB after a one-time application procedure. The cause of RDEB is a defect in the COL7A1 gene that “results in the inability to produce type VII collagen,” a press release from the manufacturer noted.

On April 22, 2024, the manufacturer Abeona Therapeutics announced that following a meeting with the FDA in March and in a subsequent request for information, the agency requires additional information to satisfy certain Chemistry Manufacturing and Controls requirements before the BLA for pz-cel can be approved. According to a press release from the company, the information pertains to validation requirements for certain manufacturing and release testing methods, including some that were observed during the FDA’s pre-licensing inspection.

The complete response letter did not identify any issues related to the clinical efficacy or safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support approval, according to the company.

The company anticipates completing the BLA resubmission in the third quarter of 2024. The application is supported by clinical efficacy and safety data from the pivotal phase 3 VIITAL study and a phase 1/2a study in patients with RDEB.

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

To the Editor:

A 56-year-old man was referred to our Grand Rounds by another dermatologist in our health system for evaluation of a red scaly rash on the trunk that had been present for more than a year. More recently, over the course of approximately 9 months he experienced recurrent painful penile ulcers that lasted for approximately 4 weeks and then self-resolved. He had a medical history of central retinal vein occlusion, primary hyperparathyroidism, and nonspecific colitis. A family history was notable for lung cancer in the patient’s father and myelodysplastic syndrome and breast cancer in his mother; however, there was no family history of a similar rash. A bacterial culture of the penile ulcer was negative. Testing for antibodies against HIV and herpes simplex virus (HSV) types 1 and 2 was negative. Results of a serum VDRL test were nonreactive, which ruled out syphilis. The patient was treated by the referring dermatologist with azithromycin for possible chancroid without relief.

The patient was being followed by the referring dermatologist who initially was concerned for Degos disease based on clinical examination findings, prompting biopsy of a lesion on the back, which revealed vacuolar interface dermatitis, a sparse superficial perivascular lymphocytic infiltrate, and increased mucin—all highly suspicious for connective tissue disease (Figure 1). An antinuclear antibody test was positive, with a titer of 1:640. The patient was started on prednisone and referred to rheumatology; however, further evaluation by rheumatology for an autoimmune process—including anticardiolipin antibodies—was unremarkable. A few months prior to the current presentation, he also had mildly elevated liver function test results. A colonoscopy was performed, and a biopsy revealed nonspecific colitis. A biopsy of the penile ulcer also was nonspecific, showing only ulceration and acute and chronic inflammation. No epidermal interface change was seen. Results from a Grocott-Gomori methenamine-silver stain, Treponema pallidum immunostain, and HSV polymerase chain reaction were negative for fungal organisms, spirochetes, and HSV, respectively. The differential diagnosis included trauma, aphthous ulceration, and Behçet disease. Behçet disease was suspected by the referring dermatologist, and the patient was treated with colchicine, prednisone, pimecrolimus cream, and topical lidocaine; however, the lesions persisted, and he was subsequently referred to our Grand Rounds for further evaluation.

At the current presentation, physical examination revealed several small papules with white atrophic centers and erythematous rims on the trunk and extremities (Figure 2A). An ulceration was noted on the penile shaft (Figure 2B). Further evaluation for Behçet disease, including testing for pathergy and HLA-B51, was negative. Degos disease was strongly suspected clinically, and a repeat biopsy was performed of a lesion on the abdomen, which revealed central epidermal necrosis, atrophy, and parakeratosis with an underlying wedge-shaped dermal infarct surrounded by multiple small occluded dermal vessels, perivascular inflammation, and dermal edema (Figure 3). Direct immunofluorescence was performed using antibodies against IgG, IgA, IgM, fibrinogen, albumin, and C3, which was negative. These findings from direct immunofluorescence and histopathology as well as the clinical presentation were considered compatible with Degos disease. The patient was started on aspirin and pentoxifylline. Pentoxifylline 400 mg twice daily appeared to lessen some of the pain. Pain management specialists started the patient on gabapentin.

Approximately 4 months after the Grand Rounds evaluation, during which time he continued treatment with pentoxifylline, he was admitted to the hospital for intractable nausea and vomiting. His condition acutely declined due to bowel perforation, and he was started on eculizumab 1200 mg every 14 days. Because of an increased risk for meningococcal meningitis while on this medication, he also was given erythromycin 500 mg twice daily prophylactically. He was being followed by hematology for the vasculopathy, and they were planning to monitor for any disease changes with computed tomography of the chest, abdomen, and pelvis every 3 months, as well as echocardiogram every 6 months for any development of pericardial or pleural fibrosis. Approximately 1 month later, the patient was admitted to the hospital again but died after 1 week from gastrointestinal complications (approximately 22 months after the onset of the rash).

Degos disease (atrophic papulosis) is a rare small vessel vasculopathy of unknown etiology, but complement-mediated endothelial injury plays a role.^1,2 It typically occurs in the fourth decade of life, with a slight female predominance.^3,4 The skin lesions are characteristic and described as 5- to 10-mm papules with atrophic white centers and erythematous telangiectatic rims, most commonly on the upper body and typically sparing the head, palms, and soles.¹ Penile ulceration is an uncommon cutaneous feature, with only a few cases reported in the literature.^5,6 Approximately one-third of patients will have only skin lesions, but two-thirds will develop systemic involvement 1 to 2 years after onset, with the gastrointestinal tract and central nervous system most commonly involved. For those with systemic involvement, the 5-year survival rate is approximately 55%, and the most common causes of death are bowel perforation, peritonitis, and stroke.^3,4 Because some patients appear to never develop systemic complications, Theodoridis et al⁴ proposed that the disease be classified as either malignant atrophic papulosis or benign atrophic papulosis to indicate the malignant systemic form and the benign cutaneous form, respectively.

The histopathology of Degos disease changes as the lesions evolve.⁷ Early lesions show a superficial and deep perivascular and periadnexal lymphocytic infiltrate, possible interface dermatitis, and dermal mucin resembling lupus. The more fully developed lesions show a greater degree of inflammation and interface change as well as lymphocytic vasculitis. This stage also may have epidermal atrophy and early papillary dermal sclerosis resembling lichen sclerosus. The late-stage lesions, clinically observed as papules with atrophic white centers and surrounding erythema, show the classic pathology of wedge-shaped dermal sclerosis and central epidermal atrophy with surrounding hyperkeratosis. Interface dermatitis and dermal mucin can be seen in all stages, though mucin is diminished in the later stage.

Effective treatment options are limited; however, antithrombotics or compounds that facilitate blood perfusion, such as aspirin or pentoxifylline, initially can be used.¹ Eculizumab, a humanized monoclonal antibody that prevents the cleavage of C5, has been used for salvage therapy,⁸ as in our case. Treprostinil, a prostacyclin analog that causes arterial vasodilation and inhibition of platelet aggregation, has been reported to improve bowel and cutaneous lesions, functional status, and neurologic symptoms.⁹

Our case highlights important features of Degos disease. First, it is important for both the clinician and the pathologist to recognize that the histopathology of Degos disease changes as the lesions evolve. In our case, although the lesions were characteristic of Degos disease clinically, the initial biopsy was suspicious for connective tissue disease, which led to an autoimmune evaluation that ultimately was unremarkable. Recognizing that early lesions of Degos disease can resemble connective tissue disease histologically could have prevented this delay in diagnosis. However, Degos disease has been reported in association with autoimmune diseases.¹⁰ Second, although penile ulceration is uncommon, it can be a prominent cutaneous manifestation of the disease. Finally, eculizumab and treprostinil are therapeutic options that have shown some efficacy in improving symptoms and cutaneous lesions.^8,9

To the Editor:

A 56-year-old man was referred to our Grand Rounds by another dermatologist in our health system for evaluation of a red scaly rash on the trunk that had been present for more than a year. More recently, over the course of approximately 9 months he experienced recurrent painful penile ulcers that lasted for approximately 4 weeks and then self-resolved. He had a medical history of central retinal vein occlusion, primary hyperparathyroidism, and nonspecific colitis. A family history was notable for lung cancer in the patient’s father and myelodysplastic syndrome and breast cancer in his mother; however, there was no family history of a similar rash. A bacterial culture of the penile ulcer was negative. Testing for antibodies against HIV and herpes simplex virus (HSV) types 1 and 2 was negative. Results of a serum VDRL test were nonreactive, which ruled out syphilis. The patient was treated by the referring dermatologist with azithromycin for possible chancroid without relief.

The patient was being followed by the referring dermatologist who initially was concerned for Degos disease based on clinical examination findings, prompting biopsy of a lesion on the back, which revealed vacuolar interface dermatitis, a sparse superficial perivascular lymphocytic infiltrate, and increased mucin—all highly suspicious for connective tissue disease (Figure 1). An antinuclear antibody test was positive, with a titer of 1:640. The patient was started on prednisone and referred to rheumatology; however, further evaluation by rheumatology for an autoimmune process—including anticardiolipin antibodies—was unremarkable. A few months prior to the current presentation, he also had mildly elevated liver function test results. A colonoscopy was performed, and a biopsy revealed nonspecific colitis. A biopsy of the penile ulcer also was nonspecific, showing only ulceration and acute and chronic inflammation. No epidermal interface change was seen. Results from a Grocott-Gomori methenamine-silver stain, Treponema pallidum immunostain, and HSV polymerase chain reaction were negative for fungal organisms, spirochetes, and HSV, respectively. The differential diagnosis included trauma, aphthous ulceration, and Behçet disease. Behçet disease was suspected by the referring dermatologist, and the patient was treated with colchicine, prednisone, pimecrolimus cream, and topical lidocaine; however, the lesions persisted, and he was subsequently referred to our Grand Rounds for further evaluation.

At the current presentation, physical examination revealed several small papules with white atrophic centers and erythematous rims on the trunk and extremities (Figure 2A). An ulceration was noted on the penile shaft (Figure 2B). Further evaluation for Behçet disease, including testing for pathergy and HLA-B51, was negative. Degos disease was strongly suspected clinically, and a repeat biopsy was performed of a lesion on the abdomen, which revealed central epidermal necrosis, atrophy, and parakeratosis with an underlying wedge-shaped dermal infarct surrounded by multiple small occluded dermal vessels, perivascular inflammation, and dermal edema (Figure 3). Direct immunofluorescence was performed using antibodies against IgG, IgA, IgM, fibrinogen, albumin, and C3, which was negative. These findings from direct immunofluorescence and histopathology as well as the clinical presentation were considered compatible with Degos disease. The patient was started on aspirin and pentoxifylline. Pentoxifylline 400 mg twice daily appeared to lessen some of the pain. Pain management specialists started the patient on gabapentin.

Approximately 4 months after the Grand Rounds evaluation, during which time he continued treatment with pentoxifylline, he was admitted to the hospital for intractable nausea and vomiting. His condition acutely declined due to bowel perforation, and he was started on eculizumab 1200 mg every 14 days. Because of an increased risk for meningococcal meningitis while on this medication, he also was given erythromycin 500 mg twice daily prophylactically. He was being followed by hematology for the vasculopathy, and they were planning to monitor for any disease changes with computed tomography of the chest, abdomen, and pelvis every 3 months, as well as echocardiogram every 6 months for any development of pericardial or pleural fibrosis. Approximately 1 month later, the patient was admitted to the hospital again but died after 1 week from gastrointestinal complications (approximately 22 months after the onset of the rash).

Degos disease (atrophic papulosis) is a rare small vessel vasculopathy of unknown etiology, but complement-mediated endothelial injury plays a role.^1,2 It typically occurs in the fourth decade of life, with a slight female predominance.^3,4 The skin lesions are characteristic and described as 5- to 10-mm papules with atrophic white centers and erythematous telangiectatic rims, most commonly on the upper body and typically sparing the head, palms, and soles.¹ Penile ulceration is an uncommon cutaneous feature, with only a few cases reported in the literature.^5,6 Approximately one-third of patients will have only skin lesions, but two-thirds will develop systemic involvement 1 to 2 years after onset, with the gastrointestinal tract and central nervous system most commonly involved. For those with systemic involvement, the 5-year survival rate is approximately 55%, and the most common causes of death are bowel perforation, peritonitis, and stroke.^3,4 Because some patients appear to never develop systemic complications, Theodoridis et al⁴ proposed that the disease be classified as either malignant atrophic papulosis or benign atrophic papulosis to indicate the malignant systemic form and the benign cutaneous form, respectively.

The histopathology of Degos disease changes as the lesions evolve.⁷ Early lesions show a superficial and deep perivascular and periadnexal lymphocytic infiltrate, possible interface dermatitis, and dermal mucin resembling lupus. The more fully developed lesions show a greater degree of inflammation and interface change as well as lymphocytic vasculitis. This stage also may have epidermal atrophy and early papillary dermal sclerosis resembling lichen sclerosus. The late-stage lesions, clinically observed as papules with atrophic white centers and surrounding erythema, show the classic pathology of wedge-shaped dermal sclerosis and central epidermal atrophy with surrounding hyperkeratosis. Interface dermatitis and dermal mucin can be seen in all stages, though mucin is diminished in the later stage.

Effective treatment options are limited; however, antithrombotics or compounds that facilitate blood perfusion, such as aspirin or pentoxifylline, initially can be used.¹ Eculizumab, a humanized monoclonal antibody that prevents the cleavage of C5, has been used for salvage therapy,⁸ as in our case. Treprostinil, a prostacyclin analog that causes arterial vasodilation and inhibition of platelet aggregation, has been reported to improve bowel and cutaneous lesions, functional status, and neurologic symptoms.⁹

Our case highlights important features of Degos disease. First, it is important for both the clinician and the pathologist to recognize that the histopathology of Degos disease changes as the lesions evolve. In our case, although the lesions were characteristic of Degos disease clinically, the initial biopsy was suspicious for connective tissue disease, which led to an autoimmune evaluation that ultimately was unremarkable. Recognizing that early lesions of Degos disease can resemble connective tissue disease histologically could have prevented this delay in diagnosis. However, Degos disease has been reported in association with autoimmune diseases.¹⁰ Second, although penile ulceration is uncommon, it can be a prominent cutaneous manifestation of the disease. Finally, eculizumab and treprostinil are therapeutic options that have shown some efficacy in improving symptoms and cutaneous lesions.^8,9

To the Editor:

A 56-year-old man was referred to our Grand Rounds by another dermatologist in our health system for evaluation of a red scaly rash on the trunk that had been present for more than a year. More recently, over the course of approximately 9 months he experienced recurrent painful penile ulcers that lasted for approximately 4 weeks and then self-resolved. He had a medical history of central retinal vein occlusion, primary hyperparathyroidism, and nonspecific colitis. A family history was notable for lung cancer in the patient’s father and myelodysplastic syndrome and breast cancer in his mother; however, there was no family history of a similar rash. A bacterial culture of the penile ulcer was negative. Testing for antibodies against HIV and herpes simplex virus (HSV) types 1 and 2 was negative. Results of a serum VDRL test were nonreactive, which ruled out syphilis. The patient was treated by the referring dermatologist with azithromycin for possible chancroid without relief.

The patient was being followed by the referring dermatologist who initially was concerned for Degos disease based on clinical examination findings, prompting biopsy of a lesion on the back, which revealed vacuolar interface dermatitis, a sparse superficial perivascular lymphocytic infiltrate, and increased mucin—all highly suspicious for connective tissue disease (Figure 1). An antinuclear antibody test was positive, with a titer of 1:640. The patient was started on prednisone and referred to rheumatology; however, further evaluation by rheumatology for an autoimmune process—including anticardiolipin antibodies—was unremarkable. A few months prior to the current presentation, he also had mildly elevated liver function test results. A colonoscopy was performed, and a biopsy revealed nonspecific colitis. A biopsy of the penile ulcer also was nonspecific, showing only ulceration and acute and chronic inflammation. No epidermal interface change was seen. Results from a Grocott-Gomori methenamine-silver stain, Treponema pallidum immunostain, and HSV polymerase chain reaction were negative for fungal organisms, spirochetes, and HSV, respectively. The differential diagnosis included trauma, aphthous ulceration, and Behçet disease. Behçet disease was suspected by the referring dermatologist, and the patient was treated with colchicine, prednisone, pimecrolimus cream, and topical lidocaine; however, the lesions persisted, and he was subsequently referred to our Grand Rounds for further evaluation.

At the current presentation, physical examination revealed several small papules with white atrophic centers and erythematous rims on the trunk and extremities (Figure 2A). An ulceration was noted on the penile shaft (Figure 2B). Further evaluation for Behçet disease, including testing for pathergy and HLA-B51, was negative. Degos disease was strongly suspected clinically, and a repeat biopsy was performed of a lesion on the abdomen, which revealed central epidermal necrosis, atrophy, and parakeratosis with an underlying wedge-shaped dermal infarct surrounded by multiple small occluded dermal vessels, perivascular inflammation, and dermal edema (Figure 3). Direct immunofluorescence was performed using antibodies against IgG, IgA, IgM, fibrinogen, albumin, and C3, which was negative. These findings from direct immunofluorescence and histopathology as well as the clinical presentation were considered compatible with Degos disease. The patient was started on aspirin and pentoxifylline. Pentoxifylline 400 mg twice daily appeared to lessen some of the pain. Pain management specialists started the patient on gabapentin.

Approximately 4 months after the Grand Rounds evaluation, during which time he continued treatment with pentoxifylline, he was admitted to the hospital for intractable nausea and vomiting. His condition acutely declined due to bowel perforation, and he was started on eculizumab 1200 mg every 14 days. Because of an increased risk for meningococcal meningitis while on this medication, he also was given erythromycin 500 mg twice daily prophylactically. He was being followed by hematology for the vasculopathy, and they were planning to monitor for any disease changes with computed tomography of the chest, abdomen, and pelvis every 3 months, as well as echocardiogram every 6 months for any development of pericardial or pleural fibrosis. Approximately 1 month later, the patient was admitted to the hospital again but died after 1 week from gastrointestinal complications (approximately 22 months after the onset of the rash).

Degos disease (atrophic papulosis) is a rare small vessel vasculopathy of unknown etiology, but complement-mediated endothelial injury plays a role.^1,2 It typically occurs in the fourth decade of life, with a slight female predominance.^3,4 The skin lesions are characteristic and described as 5- to 10-mm papules with atrophic white centers and erythematous telangiectatic rims, most commonly on the upper body and typically sparing the head, palms, and soles.¹ Penile ulceration is an uncommon cutaneous feature, with only a few cases reported in the literature.^5,6 Approximately one-third of patients will have only skin lesions, but two-thirds will develop systemic involvement 1 to 2 years after onset, with the gastrointestinal tract and central nervous system most commonly involved. For those with systemic involvement, the 5-year survival rate is approximately 55%, and the most common causes of death are bowel perforation, peritonitis, and stroke.^3,4 Because some patients appear to never develop systemic complications, Theodoridis et al⁴ proposed that the disease be classified as either malignant atrophic papulosis or benign atrophic papulosis to indicate the malignant systemic form and the benign cutaneous form, respectively.

The histopathology of Degos disease changes as the lesions evolve.⁷ Early lesions show a superficial and deep perivascular and periadnexal lymphocytic infiltrate, possible interface dermatitis, and dermal mucin resembling lupus. The more fully developed lesions show a greater degree of inflammation and interface change as well as lymphocytic vasculitis. This stage also may have epidermal atrophy and early papillary dermal sclerosis resembling lichen sclerosus. The late-stage lesions, clinically observed as papules with atrophic white centers and surrounding erythema, show the classic pathology of wedge-shaped dermal sclerosis and central epidermal atrophy with surrounding hyperkeratosis. Interface dermatitis and dermal mucin can be seen in all stages, though mucin is diminished in the later stage.

Effective treatment options are limited; however, antithrombotics or compounds that facilitate blood perfusion, such as aspirin or pentoxifylline, initially can be used.¹ Eculizumab, a humanized monoclonal antibody that prevents the cleavage of C5, has been used for salvage therapy,⁸ as in our case. Treprostinil, a prostacyclin analog that causes arterial vasodilation and inhibition of platelet aggregation, has been reported to improve bowel and cutaneous lesions, functional status, and neurologic symptoms.⁹

Our case highlights important features of Degos disease. First, it is important for both the clinician and the pathologist to recognize that the histopathology of Degos disease changes as the lesions evolve. In our case, although the lesions were characteristic of Degos disease clinically, the initial biopsy was suspicious for connective tissue disease, which led to an autoimmune evaluation that ultimately was unremarkable. Recognizing that early lesions of Degos disease can resemble connective tissue disease histologically could have prevented this delay in diagnosis. However, Degos disease has been reported in association with autoimmune diseases.¹⁰ Second, although penile ulceration is uncommon, it can be a prominent cutaneous manifestation of the disease. Finally, eculizumab and treprostinil are therapeutic options that have shown some efficacy in improving symptoms and cutaneous lesions.^8,9