Cutis

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

To the Editor:

Patients with primary psychiatric disorders with dermatologic manifestations often seek treatment from dermatologists instead of psychiatrists.¹ For example, patients with delusions of parasitosis may lack insight into the underlying etiology of their disease and instead fixate on establishing an organic cause for their symptoms. As a result, it is an increasingly common practice for dermatologists to diagnose and treat psychiatric conditions.¹ The goal of this study was to evaluate trends for the top 5 antipsychotics most frequently prescribed by dermatologists in the Medicare Part D database.

In this retrospective analysis, we consulted the Medicare Provider Utilization and Payment Data for January 2013 through December 2020, which is provided to the public by the Centers for Medicare & Medicaid Services.² Only prescribing data from dermatologists were included in this study by using the built-in filter on the website to select “dermatology” as the prescriber type. All other provider types were excluded. We chose the top 5 most prescribed antipsychotics based on the number of supply days reported. Supply days—defined by Medicare as the number of days’ worth of medication that is prescribed—were used as a metric for ­utilization; therefore, each drug’s total supply days prescribed by dermatologists were calculated using this combined filter of drug name and total supply days using the database.

To analyze utilization over time, the annual average growth rate (AAGR) was calculated by determining the growth rate in total supply days annually from 2013 to 2020 and then averaging those rates to determine the overall AAGR. For greater clinical relevance, we calculated the average growth in supply days for the entire study period by determining the difference in the number of supply days for each year and then averaging these values. This was done to consider overall trends across dermatology rather than individual dermatologist prescribing patterns.

Based on our analysis, the antipsychotics most frequently prescribed by dermatologists for Medicare patients from January 2013 to December 2020 were pimozide, quetiapine, risperidone, olanzapine, and aripiprazole. The AAGR for each drug was 2.35%, 4.89%, 5.59%, 9.48%, and 20.72%, respectively, which is consistent with increased utilization over the study period for all 5 drugs (Table 1). The change in cost per supply day for the same period was 1.3%, –66.1%, –60.2%, –81.7%, and –84.3%, respectively. The net difference in cost per supply day over this entire period was $0.02, –$2.79, –$1.06, –$5.37, and –$21.22, respectively (Table 2).

To the Editor:

Patients with primary psychiatric disorders with dermatologic manifestations often seek treatment from dermatologists instead of psychiatrists.¹ For example, patients with delusions of parasitosis may lack insight into the underlying etiology of their disease and instead fixate on establishing an organic cause for their symptoms. As a result, it is an increasingly common practice for dermatologists to diagnose and treat psychiatric conditions.¹ The goal of this study was to evaluate trends for the top 5 antipsychotics most frequently prescribed by dermatologists in the Medicare Part D database.

In this retrospective analysis, we consulted the Medicare Provider Utilization and Payment Data for January 2013 through December 2020, which is provided to the public by the Centers for Medicare & Medicaid Services.² Only prescribing data from dermatologists were included in this study by using the built-in filter on the website to select “dermatology” as the prescriber type. All other provider types were excluded. We chose the top 5 most prescribed antipsychotics based on the number of supply days reported. Supply days—defined by Medicare as the number of days’ worth of medication that is prescribed—were used as a metric for ­utilization; therefore, each drug’s total supply days prescribed by dermatologists were calculated using this combined filter of drug name and total supply days using the database.

To analyze utilization over time, the annual average growth rate (AAGR) was calculated by determining the growth rate in total supply days annually from 2013 to 2020 and then averaging those rates to determine the overall AAGR. For greater clinical relevance, we calculated the average growth in supply days for the entire study period by determining the difference in the number of supply days for each year and then averaging these values. This was done to consider overall trends across dermatology rather than individual dermatologist prescribing patterns.

Based on our analysis, the antipsychotics most frequently prescribed by dermatologists for Medicare patients from January 2013 to December 2020 were pimozide, quetiapine, risperidone, olanzapine, and aripiprazole. The AAGR for each drug was 2.35%, 4.89%, 5.59%, 9.48%, and 20.72%, respectively, which is consistent with increased utilization over the study period for all 5 drugs (Table 1). The change in cost per supply day for the same period was 1.3%, –66.1%, –60.2%, –81.7%, and –84.3%, respectively. The net difference in cost per supply day over this entire period was $0.02, –$2.79, –$1.06, –$5.37, and –$21.22, respectively (Table 2).

To the Editor:

Patients with primary psychiatric disorders with dermatologic manifestations often seek treatment from dermatologists instead of psychiatrists.¹ For example, patients with delusions of parasitosis may lack insight into the underlying etiology of their disease and instead fixate on establishing an organic cause for their symptoms. As a result, it is an increasingly common practice for dermatologists to diagnose and treat psychiatric conditions.¹ The goal of this study was to evaluate trends for the top 5 antipsychotics most frequently prescribed by dermatologists in the Medicare Part D database.

In this retrospective analysis, we consulted the Medicare Provider Utilization and Payment Data for January 2013 through December 2020, which is provided to the public by the Centers for Medicare & Medicaid Services.² Only prescribing data from dermatologists were included in this study by using the built-in filter on the website to select “dermatology” as the prescriber type. All other provider types were excluded. We chose the top 5 most prescribed antipsychotics based on the number of supply days reported. Supply days—defined by Medicare as the number of days’ worth of medication that is prescribed—were used as a metric for ­utilization; therefore, each drug’s total supply days prescribed by dermatologists were calculated using this combined filter of drug name and total supply days using the database.

To analyze utilization over time, the annual average growth rate (AAGR) was calculated by determining the growth rate in total supply days annually from 2013 to 2020 and then averaging those rates to determine the overall AAGR. For greater clinical relevance, we calculated the average growth in supply days for the entire study period by determining the difference in the number of supply days for each year and then averaging these values. This was done to consider overall trends across dermatology rather than individual dermatologist prescribing patterns.

Based on our analysis, the antipsychotics most frequently prescribed by dermatologists for Medicare patients from January 2013 to December 2020 were pimozide, quetiapine, risperidone, olanzapine, and aripiprazole. The AAGR for each drug was 2.35%, 4.89%, 5.59%, 9.48%, and 20.72%, respectively, which is consistent with increased utilization over the study period for all 5 drugs (Table 1). The change in cost per supply day for the same period was 1.3%, –66.1%, –60.2%, –81.7%, and –84.3%, respectively. The net difference in cost per supply day over this entire period was $0.02, –$2.79, –$1.06, –$5.37, and –$21.22, respectively (Table 2).

To the Editor:

Gonococcal infections, which are caused by the sexually transmitted, gram-negative diplococcus Neisseria gonorrhoeae, are a current and increasing threat to public health. Between 2012 and 2021, the rate of gonococcal infection in the United States increased 137.8% in men and 64.9% in women,¹ with an estimated 1.5 million new gonococcal infections occurring each year in the United States as of 2021.²Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection (STI), and patients with gonococcal infection frequently are coinfected with Chlamydia trachomatis, which is the most common bacterial STI. Uncomplicated gonococcal infection (also known as gonorrhea) most commonly causes asymptomatic cervicovaginal infection in women and symptomatic urethral infection in men.² Other uncomplicated manifestations include rectal infection, which can be asymptomatic or manifest with anal pruritus, anal discharge, or tenesmus, and oropharyngeal infection, which can be asymptomatic or manifest with throat pain. If uncomplicated gonococcal infections are left untreated or are incompletely treated, serious complications including septic arthritis, myositis, osteomyelitis, myocarditis, endocarditis, and meningitis might occur.^2-5 Ascending, locally invasive infections can cause epididymitis or pelvic inflammatory disease, which is an important cause of infertility in women.^2,3 Gonococcal conjunctivitis also can occur, particularly when neonates are exposed to bacteria during vaginal delivery. Although rare, gonococcal bacteria can disseminate widely, with an estimated 0.5% to 3% of uncomplicated gonococcal infections progressing to disseminated gonococcal infection (DGI).^3-6 Because DGI can mimic other systemic conditions, including a variety of bacterial and viral infections as well as inflammatory conditions, it can be difficult to diagnose without a high index of clinical suspicion. We present a case of DGI diagnosed based on dermatologic expertise and pharyngeal molecular testing.

A 30-year-old man presented to the emergency department with a rash on the extremeities as well as emesis, fever, sore throat, and severe arthralgia in the wrists, hands, knees, and feet of 2 days’ duration. The patient also had experienced several months of dysuria. He reported daily use of the recreational drug ketamine, multiple new male sexual partners, and unprotected oral and receptive anal sex in recent months. He denied any history of STIs. Physical examination demonstrated tender edematous wrists and fingers, papulovesicles on erythematous bases on the palms, and purpuric macules scattered on the legs (Figure 1). The patient also had tonsillar edema with notable white tonsillar exudate.

To the Editor:

Gonococcal infections, which are caused by the sexually transmitted, gram-negative diplococcus Neisseria gonorrhoeae, are a current and increasing threat to public health. Between 2012 and 2021, the rate of gonococcal infection in the United States increased 137.8% in men and 64.9% in women,¹ with an estimated 1.5 million new gonococcal infections occurring each year in the United States as of 2021.²Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection (STI), and patients with gonococcal infection frequently are coinfected with Chlamydia trachomatis, which is the most common bacterial STI. Uncomplicated gonococcal infection (also known as gonorrhea) most commonly causes asymptomatic cervicovaginal infection in women and symptomatic urethral infection in men.² Other uncomplicated manifestations include rectal infection, which can be asymptomatic or manifest with anal pruritus, anal discharge, or tenesmus, and oropharyngeal infection, which can be asymptomatic or manifest with throat pain. If uncomplicated gonococcal infections are left untreated or are incompletely treated, serious complications including septic arthritis, myositis, osteomyelitis, myocarditis, endocarditis, and meningitis might occur.^2-5 Ascending, locally invasive infections can cause epididymitis or pelvic inflammatory disease, which is an important cause of infertility in women.^2,3 Gonococcal conjunctivitis also can occur, particularly when neonates are exposed to bacteria during vaginal delivery. Although rare, gonococcal bacteria can disseminate widely, with an estimated 0.5% to 3% of uncomplicated gonococcal infections progressing to disseminated gonococcal infection (DGI).^3-6 Because DGI can mimic other systemic conditions, including a variety of bacterial and viral infections as well as inflammatory conditions, it can be difficult to diagnose without a high index of clinical suspicion. We present a case of DGI diagnosed based on dermatologic expertise and pharyngeal molecular testing.

A 30-year-old man presented to the emergency department with a rash on the extremeities as well as emesis, fever, sore throat, and severe arthralgia in the wrists, hands, knees, and feet of 2 days’ duration. The patient also had experienced several months of dysuria. He reported daily use of the recreational drug ketamine, multiple new male sexual partners, and unprotected oral and receptive anal sex in recent months. He denied any history of STIs. Physical examination demonstrated tender edematous wrists and fingers, papulovesicles on erythematous bases on the palms, and purpuric macules scattered on the legs (Figure 1). The patient also had tonsillar edema with notable white tonsillar exudate.

To the Editor:

Gonococcal infections, which are caused by the sexually transmitted, gram-negative diplococcus Neisseria gonorrhoeae, are a current and increasing threat to public health. Between 2012 and 2021, the rate of gonococcal infection in the United States increased 137.8% in men and 64.9% in women,¹ with an estimated 1.5 million new gonococcal infections occurring each year in the United States as of 2021.²Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection (STI), and patients with gonococcal infection frequently are coinfected with Chlamydia trachomatis, which is the most common bacterial STI. Uncomplicated gonococcal infection (also known as gonorrhea) most commonly causes asymptomatic cervicovaginal infection in women and symptomatic urethral infection in men.² Other uncomplicated manifestations include rectal infection, which can be asymptomatic or manifest with anal pruritus, anal discharge, or tenesmus, and oropharyngeal infection, which can be asymptomatic or manifest with throat pain. If uncomplicated gonococcal infections are left untreated or are incompletely treated, serious complications including septic arthritis, myositis, osteomyelitis, myocarditis, endocarditis, and meningitis might occur.^2-5 Ascending, locally invasive infections can cause epididymitis or pelvic inflammatory disease, which is an important cause of infertility in women.^2,3 Gonococcal conjunctivitis also can occur, particularly when neonates are exposed to bacteria during vaginal delivery. Although rare, gonococcal bacteria can disseminate widely, with an estimated 0.5% to 3% of uncomplicated gonococcal infections progressing to disseminated gonococcal infection (DGI).^3-6 Because DGI can mimic other systemic conditions, including a variety of bacterial and viral infections as well as inflammatory conditions, it can be difficult to diagnose without a high index of clinical suspicion. We present a case of DGI diagnosed based on dermatologic expertise and pharyngeal molecular testing.

A 30-year-old man presented to the emergency department with a rash on the extremeities as well as emesis, fever, sore throat, and severe arthralgia in the wrists, hands, knees, and feet of 2 days’ duration. The patient also had experienced several months of dysuria. He reported daily use of the recreational drug ketamine, multiple new male sexual partners, and unprotected oral and receptive anal sex in recent months. He denied any history of STIs. Physical examination demonstrated tender edematous wrists and fingers, papulovesicles on erythematous bases on the palms, and purpuric macules scattered on the legs (Figure 1). The patient also had tonsillar edema with notable white tonsillar exudate.

Biologics have revolutionized dermatologic treatment, offering substantial relief from chronic and ­debilitating skin conditions such as psoriasis, hidradenitis suppurativa, atopic dermatitis (AD), chronic urticaria, and immunobullous diseases (eg, pemphigus vulgaris, bullous pemphigoid). By drastically decreasing symptom burden, biologics have the potential to transform patients’ lives by improving their overall quality of life (QOL). However, the use of biologics during ­pregnancy raises critical considerations, especially ­regarding safety.

Biologics for Cutaneous Conditions

Biologics—tumor necrosis factor (TNF) α inhibitors; IL-17, IL-23, IL-12, and IL-36 inhibitors; and agents such as omalizumab and dupilumab—have shown remarkable efficacy in controlling severe or recalcitrant dermatologic conditions and typically are more effective than traditional systemic therapies.¹ For instance, randomized clinical trials (RCTs) and real-world data have shown that patients with psoriasis can achieve considerable skin clearance with biologics, greatly enhancing QOL.² Adalimumab and secukinumab, which have been approved for use in moderate to severe cases of hidradenitis suppurativa, reduce the frequency of painful nodules and abscesses, thereby decreasing pain and improving QOL. Dupilumab, an IL-4/13 receptor antagonist, has revolutionized the treatment of AD by drastically reducing itch and skin lesions and improving QOL.³ For chronic urticaria, the anti-IgE antibody omalizumab has effectively reduced the incidence of hives and itching, providing pronounced symptom relief when traditional antihistamines fail.⁴ Use of rituximab, an anti-CD20 monoclonal antibody, has led to remission in severe cases of pemphigus vulgaris and bullous pemphigoid.⁵

Impact of Untreated Cutaneous Conditions in Pregnancy

When treating patients who are pregnant, dermatologists must consider the health of both the expectant mother and the developing fetus. This dual focus complicates decision-making, particularly with the use of biologics. Untreated cutaneous conditions can profoundly impact a pregnant patient’s health and QOL as well as lead to pregnancy complications affecting the fetus, such as preterm birth or low birth weight. In some studies, moderate to severe psoriasis has been associated with increased risk for complications during pregnancy, including preeclampsia and intrauterine growth restriction.⁶ Although specific data on hidradenitis suppurativa are lacking, the highly inflammatory nature of the condition suggests similar adverse effects on pregnancy.⁷ Atopic dermatitis can be exacerbated during pregnancy due to a shift in the immune system to become more allergic dominant.⁸ Generalized pustular psoriasis manifests with widespread pustules, fever, and systemic inflammation, posing serious risks to both the mother and the fetus if left untreated⁹; in such a life-threatening scenario, the use of potent treatments such as spesolimab, an IL-36 receptor antagonist, may be warranted. Therefore, managing these conditions effectively is crucial not only for the mother’s health but also for fetal well-being.

Which Biologics Can Dermatologists Safely Prescribe?

Despite the benefits, many dermatologists are hesitant to prescribe biologics to pregnant patients due to the lack of understanding and definitive safety data.^10,11 Although there are no RCTs that involve pregnant patients, current evidence suggests that several biologics are not teratogenic and do not cause fetal malformations. Extensive postexposure data support the safety of TNF-α inhibitors during pregnancy.¹² Research has shown that children exposed to these agents in utero have normal development, infection rates, and vaccination outcomes comparable to nonexposed children. For example, a systematic review and meta-analysis found no significant increase in the risk for major congenital malformations, spontaneous abortions, or preterm births among patients exposed to anti–TNF-α agents during pregnancy.² The Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project has provided valuable real-world data indicating that the use of TNF-α inhibitors in pregnancy, particularly during the first trimester, does not substantially elevate the risk for adverse outcomes.¹³ These findings have been corroborated by several other registry studies and RCTs, providing a robust safety profile for these agents during pregnancy.¹⁴

Similarly, postexposure data on IL-17 and IL-12/23 inhibitors indicate a favorable safety profile, though the sample sizes are smaller than those for anti–TNF-α agents.^12,14 Studies of drugs such as secukinumab (IL-17 inhibitor), guselkumab (IL-23 inhibitor), or ustekinumab (IL-12/23 inhibitor) have shown no association with teratogenic effects or increased risk for miscarriage.¹⁴ However, agents such as spesolimab (IL-36 inhibitor) are relatively new, and ongoing studies are expected to provide more comprehensive safety data.¹⁵ Similarly, omalizumab and dupilumab have not been associated with increased risk for fetal malformations or adverse pregnancy outcomes. Omalizumab, indicated for chronic urticaria, has a good safety profile in pregnancy, with no significant increase in adverse outcomes reported in studies and registries.¹⁶ Dupilumab, used for AD, has demonstrated safety in pregnancy, with ongoing studies continuing to monitor outcomes.¹⁷

Conversely, rituximab (an anti-CD20 antibody for autoimmune bullous diseases) has shown evidence of adverse pregnancy outcomes, including fetal harm.¹⁸ Its use generally is discouraged unless deemed absolutely necessary, and no safer alternatives are available. Rituximab can cross the placenta, especially in the second and third trimesters, and has been associated with B-cell depletion in the fetus, leading to potential immunosuppression and increased risk for infections.⁵

Although the data on the safety of biologics in pregnancy are largely reassuring, it is essential to recognize that potential risks have not been ruled out entirely. There are extensive safety data for anti–TNF-α inhibitors, which provides a level of confidence; although newer agents such as IL-17 and IL-23 inhibitors have shown promising early results, further research is required to solidify their safety profiles during pregnancy.

Dermatologists must balance the risks and benefits of using biologics in pregnant patients. This decision-­making process involves careful consideration of the severity of the mother’s condition, the potential risks to the fetus, and the availability of alternative treatments. For many severe dermatologic conditions, the benefits of biologics in controlling disease activity and improving QOL may outweigh the potential risks, especially when other treatments have failed or are not suitable.

Final Thoughts

The increasing use of biologics in dermatology has undoubtedly improved the management of severe skin conditions, substantially enhancing patients’ QOL. As more data become available and clinical guidelines evolve, health care providers will be better equipped to make informed decisions about the use of biologics, particularly in pregnant patients. Collaborative efforts between dermatologists, obstetricians, and researchers will help refine treatment guidelines and ensure that pregnant patients with severe dermatologic conditions receive the best possible care.

For now, although the current evidence supports the safety of many biologics during pregnancy,^10,11 individualized care and informed decision-making remain paramount. Careful management and adherence to current guidelines make it possible to navigate the complexities of treating severe dermatologic conditions in pregnant patients, ensuring the best outcomes for both mother and child.

Biologics have revolutionized dermatologic treatment, offering substantial relief from chronic and ­debilitating skin conditions such as psoriasis, hidradenitis suppurativa, atopic dermatitis (AD), chronic urticaria, and immunobullous diseases (eg, pemphigus vulgaris, bullous pemphigoid). By drastically decreasing symptom burden, biologics have the potential to transform patients’ lives by improving their overall quality of life (QOL). However, the use of biologics during ­pregnancy raises critical considerations, especially ­regarding safety.

Biologics for Cutaneous Conditions

Biologics—tumor necrosis factor (TNF) α inhibitors; IL-17, IL-23, IL-12, and IL-36 inhibitors; and agents such as omalizumab and dupilumab—have shown remarkable efficacy in controlling severe or recalcitrant dermatologic conditions and typically are more effective than traditional systemic therapies.¹ For instance, randomized clinical trials (RCTs) and real-world data have shown that patients with psoriasis can achieve considerable skin clearance with biologics, greatly enhancing QOL.² Adalimumab and secukinumab, which have been approved for use in moderate to severe cases of hidradenitis suppurativa, reduce the frequency of painful nodules and abscesses, thereby decreasing pain and improving QOL. Dupilumab, an IL-4/13 receptor antagonist, has revolutionized the treatment of AD by drastically reducing itch and skin lesions and improving QOL.³ For chronic urticaria, the anti-IgE antibody omalizumab has effectively reduced the incidence of hives and itching, providing pronounced symptom relief when traditional antihistamines fail.⁴ Use of rituximab, an anti-CD20 monoclonal antibody, has led to remission in severe cases of pemphigus vulgaris and bullous pemphigoid.⁵

Impact of Untreated Cutaneous Conditions in Pregnancy

When treating patients who are pregnant, dermatologists must consider the health of both the expectant mother and the developing fetus. This dual focus complicates decision-making, particularly with the use of biologics. Untreated cutaneous conditions can profoundly impact a pregnant patient’s health and QOL as well as lead to pregnancy complications affecting the fetus, such as preterm birth or low birth weight. In some studies, moderate to severe psoriasis has been associated with increased risk for complications during pregnancy, including preeclampsia and intrauterine growth restriction.⁶ Although specific data on hidradenitis suppurativa are lacking, the highly inflammatory nature of the condition suggests similar adverse effects on pregnancy.⁷ Atopic dermatitis can be exacerbated during pregnancy due to a shift in the immune system to become more allergic dominant.⁸ Generalized pustular psoriasis manifests with widespread pustules, fever, and systemic inflammation, posing serious risks to both the mother and the fetus if left untreated⁹; in such a life-threatening scenario, the use of potent treatments such as spesolimab, an IL-36 receptor antagonist, may be warranted. Therefore, managing these conditions effectively is crucial not only for the mother’s health but also for fetal well-being.

Which Biologics Can Dermatologists Safely Prescribe?

Despite the benefits, many dermatologists are hesitant to prescribe biologics to pregnant patients due to the lack of understanding and definitive safety data.^10,11 Although there are no RCTs that involve pregnant patients, current evidence suggests that several biologics are not teratogenic and do not cause fetal malformations. Extensive postexposure data support the safety of TNF-α inhibitors during pregnancy.¹² Research has shown that children exposed to these agents in utero have normal development, infection rates, and vaccination outcomes comparable to nonexposed children. For example, a systematic review and meta-analysis found no significant increase in the risk for major congenital malformations, spontaneous abortions, or preterm births among patients exposed to anti–TNF-α agents during pregnancy.² The Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project has provided valuable real-world data indicating that the use of TNF-α inhibitors in pregnancy, particularly during the first trimester, does not substantially elevate the risk for adverse outcomes.¹³ These findings have been corroborated by several other registry studies and RCTs, providing a robust safety profile for these agents during pregnancy.¹⁴

Similarly, postexposure data on IL-17 and IL-12/23 inhibitors indicate a favorable safety profile, though the sample sizes are smaller than those for anti–TNF-α agents.^12,14 Studies of drugs such as secukinumab (IL-17 inhibitor), guselkumab (IL-23 inhibitor), or ustekinumab (IL-12/23 inhibitor) have shown no association with teratogenic effects or increased risk for miscarriage.¹⁴ However, agents such as spesolimab (IL-36 inhibitor) are relatively new, and ongoing studies are expected to provide more comprehensive safety data.¹⁵ Similarly, omalizumab and dupilumab have not been associated with increased risk for fetal malformations or adverse pregnancy outcomes. Omalizumab, indicated for chronic urticaria, has a good safety profile in pregnancy, with no significant increase in adverse outcomes reported in studies and registries.¹⁶ Dupilumab, used for AD, has demonstrated safety in pregnancy, with ongoing studies continuing to monitor outcomes.¹⁷

Conversely, rituximab (an anti-CD20 antibody for autoimmune bullous diseases) has shown evidence of adverse pregnancy outcomes, including fetal harm.¹⁸ Its use generally is discouraged unless deemed absolutely necessary, and no safer alternatives are available. Rituximab can cross the placenta, especially in the second and third trimesters, and has been associated with B-cell depletion in the fetus, leading to potential immunosuppression and increased risk for infections.⁵

Although the data on the safety of biologics in pregnancy are largely reassuring, it is essential to recognize that potential risks have not been ruled out entirely. There are extensive safety data for anti–TNF-α inhibitors, which provides a level of confidence; although newer agents such as IL-17 and IL-23 inhibitors have shown promising early results, further research is required to solidify their safety profiles during pregnancy.

Dermatologists must balance the risks and benefits of using biologics in pregnant patients. This decision-­making process involves careful consideration of the severity of the mother’s condition, the potential risks to the fetus, and the availability of alternative treatments. For many severe dermatologic conditions, the benefits of biologics in controlling disease activity and improving QOL may outweigh the potential risks, especially when other treatments have failed or are not suitable.

Final Thoughts

The increasing use of biologics in dermatology has undoubtedly improved the management of severe skin conditions, substantially enhancing patients’ QOL. As more data become available and clinical guidelines evolve, health care providers will be better equipped to make informed decisions about the use of biologics, particularly in pregnant patients. Collaborative efforts between dermatologists, obstetricians, and researchers will help refine treatment guidelines and ensure that pregnant patients with severe dermatologic conditions receive the best possible care.

For now, although the current evidence supports the safety of many biologics during pregnancy,^10,11 individualized care and informed decision-making remain paramount. Careful management and adherence to current guidelines make it possible to navigate the complexities of treating severe dermatologic conditions in pregnant patients, ensuring the best outcomes for both mother and child.

Biologics have revolutionized dermatologic treatment, offering substantial relief from chronic and ­debilitating skin conditions such as psoriasis, hidradenitis suppurativa, atopic dermatitis (AD), chronic urticaria, and immunobullous diseases (eg, pemphigus vulgaris, bullous pemphigoid). By drastically decreasing symptom burden, biologics have the potential to transform patients’ lives by improving their overall quality of life (QOL). However, the use of biologics during ­pregnancy raises critical considerations, especially ­regarding safety.

Biologics for Cutaneous Conditions

Biologics—tumor necrosis factor (TNF) α inhibitors; IL-17, IL-23, IL-12, and IL-36 inhibitors; and agents such as omalizumab and dupilumab—have shown remarkable efficacy in controlling severe or recalcitrant dermatologic conditions and typically are more effective than traditional systemic therapies.¹ For instance, randomized clinical trials (RCTs) and real-world data have shown that patients with psoriasis can achieve considerable skin clearance with biologics, greatly enhancing QOL.² Adalimumab and secukinumab, which have been approved for use in moderate to severe cases of hidradenitis suppurativa, reduce the frequency of painful nodules and abscesses, thereby decreasing pain and improving QOL. Dupilumab, an IL-4/13 receptor antagonist, has revolutionized the treatment of AD by drastically reducing itch and skin lesions and improving QOL.³ For chronic urticaria, the anti-IgE antibody omalizumab has effectively reduced the incidence of hives and itching, providing pronounced symptom relief when traditional antihistamines fail.⁴ Use of rituximab, an anti-CD20 monoclonal antibody, has led to remission in severe cases of pemphigus vulgaris and bullous pemphigoid.⁵

Impact of Untreated Cutaneous Conditions in Pregnancy

When treating patients who are pregnant, dermatologists must consider the health of both the expectant mother and the developing fetus. This dual focus complicates decision-making, particularly with the use of biologics. Untreated cutaneous conditions can profoundly impact a pregnant patient’s health and QOL as well as lead to pregnancy complications affecting the fetus, such as preterm birth or low birth weight. In some studies, moderate to severe psoriasis has been associated with increased risk for complications during pregnancy, including preeclampsia and intrauterine growth restriction.⁶ Although specific data on hidradenitis suppurativa are lacking, the highly inflammatory nature of the condition suggests similar adverse effects on pregnancy.⁷ Atopic dermatitis can be exacerbated during pregnancy due to a shift in the immune system to become more allergic dominant.⁸ Generalized pustular psoriasis manifests with widespread pustules, fever, and systemic inflammation, posing serious risks to both the mother and the fetus if left untreated⁹; in such a life-threatening scenario, the use of potent treatments such as spesolimab, an IL-36 receptor antagonist, may be warranted. Therefore, managing these conditions effectively is crucial not only for the mother’s health but also for fetal well-being.

Which Biologics Can Dermatologists Safely Prescribe?

Despite the benefits, many dermatologists are hesitant to prescribe biologics to pregnant patients due to the lack of understanding and definitive safety data.^10,11 Although there are no RCTs that involve pregnant patients, current evidence suggests that several biologics are not teratogenic and do not cause fetal malformations. Extensive postexposure data support the safety of TNF-α inhibitors during pregnancy.¹² Research has shown that children exposed to these agents in utero have normal development, infection rates, and vaccination outcomes comparable to nonexposed children. For example, a systematic review and meta-analysis found no significant increase in the risk for major congenital malformations, spontaneous abortions, or preterm births among patients exposed to anti–TNF-α agents during pregnancy.² The Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project has provided valuable real-world data indicating that the use of TNF-α inhibitors in pregnancy, particularly during the first trimester, does not substantially elevate the risk for adverse outcomes.¹³ These findings have been corroborated by several other registry studies and RCTs, providing a robust safety profile for these agents during pregnancy.¹⁴

Similarly, postexposure data on IL-17 and IL-12/23 inhibitors indicate a favorable safety profile, though the sample sizes are smaller than those for anti–TNF-α agents.^12,14 Studies of drugs such as secukinumab (IL-17 inhibitor), guselkumab (IL-23 inhibitor), or ustekinumab (IL-12/23 inhibitor) have shown no association with teratogenic effects or increased risk for miscarriage.¹⁴ However, agents such as spesolimab (IL-36 inhibitor) are relatively new, and ongoing studies are expected to provide more comprehensive safety data.¹⁵ Similarly, omalizumab and dupilumab have not been associated with increased risk for fetal malformations or adverse pregnancy outcomes. Omalizumab, indicated for chronic urticaria, has a good safety profile in pregnancy, with no significant increase in adverse outcomes reported in studies and registries.¹⁶ Dupilumab, used for AD, has demonstrated safety in pregnancy, with ongoing studies continuing to monitor outcomes.¹⁷

Conversely, rituximab (an anti-CD20 antibody for autoimmune bullous diseases) has shown evidence of adverse pregnancy outcomes, including fetal harm.¹⁸ Its use generally is discouraged unless deemed absolutely necessary, and no safer alternatives are available. Rituximab can cross the placenta, especially in the second and third trimesters, and has been associated with B-cell depletion in the fetus, leading to potential immunosuppression and increased risk for infections.⁵

Although the data on the safety of biologics in pregnancy are largely reassuring, it is essential to recognize that potential risks have not been ruled out entirely. There are extensive safety data for anti–TNF-α inhibitors, which provides a level of confidence; although newer agents such as IL-17 and IL-23 inhibitors have shown promising early results, further research is required to solidify their safety profiles during pregnancy.

Dermatologists must balance the risks and benefits of using biologics in pregnant patients. This decision-­making process involves careful consideration of the severity of the mother’s condition, the potential risks to the fetus, and the availability of alternative treatments. For many severe dermatologic conditions, the benefits of biologics in controlling disease activity and improving QOL may outweigh the potential risks, especially when other treatments have failed or are not suitable.

Final Thoughts

The increasing use of biologics in dermatology has undoubtedly improved the management of severe skin conditions, substantially enhancing patients’ QOL. As more data become available and clinical guidelines evolve, health care providers will be better equipped to make informed decisions about the use of biologics, particularly in pregnant patients. Collaborative efforts between dermatologists, obstetricians, and researchers will help refine treatment guidelines and ensure that pregnant patients with severe dermatologic conditions receive the best possible care.

For now, although the current evidence supports the safety of many biologics during pregnancy,^10,11 individualized care and informed decision-making remain paramount. Careful management and adherence to current guidelines make it possible to navigate the complexities of treating severe dermatologic conditions in pregnant patients, ensuring the best outcomes for both mother and child.

Practice Gap

The term nail biopsy (NB) may refer to a punch, excisional, shave, or longitudinal biopsy of the nail matrix and/or nail bed.¹ Nail surgeries, including NBs, are performed relatively infrequently. In a study using data from the Medicare Provider Utilization and Payment Database 2012-2017, only 1.01% of Mohs surgeons and 0.28% of general dermatologists in the United States performed NBs. Thirty-one states had no dermatologist-performed NBs, while 3 states had no nail biopsies performed by any physician, podiatrist, nurse practitioner, or physician assistant, indicating that there is a shortage of dermatology clinicians performing nail surgeries.²

Dermatologists may not be performing NBs due to unfamiliarity with nail unit anatomy and lack of formal NB training during residency.³ In a survey of 240 dermatology residents in the United States, 58% reported performing fewer than 10 nail procedures during residency, with 25% observing only.⁴ Of those surveyed, 1% had no exposure to nail procedures during 3 years of residency. Furthermore, when asked to assess their competency in nail surgery on a scale of not competent, competent, and very competent, approximately 30% responded that they were not competent.⁴ Without sufficient education on procedures involving the nail unit, residents may be reluctant to incorporate nail surgery into their clinical practice.

Due to their complexity, NBs require the use of several specialized surgical instruments that are not used for other dermatologic procedures, and residents and attending physicians who have limited nail training may be unfamiliar with these tools. To address this educational gap, we sought to create a guide that details the surgical instruments used for the nail matrix tangential excision (shave) biopsy technique—the most common technique used in our nail specialty clinic. This guide is intended for educational use by dermatologists who wish to incorporate NB as part of their practice.

Tools and Technique

As a major referral center, our New York City–based nail specialty clinic performs a large volume of NBs, many of them performed for clinically concerning longitudinal melanonychias for which a nail matrix shave biopsy most often is performed. We utilize a standardized tray consisting of 12 surgical instruments that are needed to successfully perform a NB from start to finish (Figure). In addition to standard surgical tray items, such as sutures and tissue scissors, additional specialized instruments are necessary for NB procedures, including a nail elevator, an English nail splitter, and skin hook.

After the initial incisions are made at 45° angles to the proximal nail fold surrounding the longitudinal band, the nail elevator is used to separate the proximal nail plate from the underlying nail bed. The English nail splitter is used to create a transverse split separating the proximal from the distal nail plate, and the proximal nail plate then is retracted using a clamp. The skin hook is used to retract the proximal nail fold to expose the pigment in the nail matrix, which is biopsied using the #15 blade and sent for histopathology. The proximal nail fold and retracted nail plate then are put back in place, and absorbable sutures are used to repair the defect. In certain cases, a 3-mm punch biopsy may be used to sample the nail plate and/or the surrounding soft tissue.

Practice Implications

A guide to surgical tools used during NB procedures, including less commonly encountered tools such as a nail elevator and English nail splitter, helps to close the educational gap of NB procedures among dermatology trainees and attending physicians. In conjunction with practical training with cadavers and models, a guide to surgical tools can be reviewed by trainees before hands-on exposure to nail surgery in a clinical setting. By increasing awareness of the tools needed to complete the procedure from start to finish, dermatologists may feel more prepared and confident in their ability to perform NBs, ultimately allowing for more rapid diagnosis of nail malignancies.

Practice Gap

The term nail biopsy (NB) may refer to a punch, excisional, shave, or longitudinal biopsy of the nail matrix and/or nail bed.¹ Nail surgeries, including NBs, are performed relatively infrequently. In a study using data from the Medicare Provider Utilization and Payment Database 2012-2017, only 1.01% of Mohs surgeons and 0.28% of general dermatologists in the United States performed NBs. Thirty-one states had no dermatologist-performed NBs, while 3 states had no nail biopsies performed by any physician, podiatrist, nurse practitioner, or physician assistant, indicating that there is a shortage of dermatology clinicians performing nail surgeries.²

Dermatologists may not be performing NBs due to unfamiliarity with nail unit anatomy and lack of formal NB training during residency.³ In a survey of 240 dermatology residents in the United States, 58% reported performing fewer than 10 nail procedures during residency, with 25% observing only.⁴ Of those surveyed, 1% had no exposure to nail procedures during 3 years of residency. Furthermore, when asked to assess their competency in nail surgery on a scale of not competent, competent, and very competent, approximately 30% responded that they were not competent.⁴ Without sufficient education on procedures involving the nail unit, residents may be reluctant to incorporate nail surgery into their clinical practice.

Due to their complexity, NBs require the use of several specialized surgical instruments that are not used for other dermatologic procedures, and residents and attending physicians who have limited nail training may be unfamiliar with these tools. To address this educational gap, we sought to create a guide that details the surgical instruments used for the nail matrix tangential excision (shave) biopsy technique—the most common technique used in our nail specialty clinic. This guide is intended for educational use by dermatologists who wish to incorporate NB as part of their practice.

Tools and Technique

As a major referral center, our New York City–based nail specialty clinic performs a large volume of NBs, many of them performed for clinically concerning longitudinal melanonychias for which a nail matrix shave biopsy most often is performed. We utilize a standardized tray consisting of 12 surgical instruments that are needed to successfully perform a NB from start to finish (Figure). In addition to standard surgical tray items, such as sutures and tissue scissors, additional specialized instruments are necessary for NB procedures, including a nail elevator, an English nail splitter, and skin hook.

After the initial incisions are made at 45° angles to the proximal nail fold surrounding the longitudinal band, the nail elevator is used to separate the proximal nail plate from the underlying nail bed. The English nail splitter is used to create a transverse split separating the proximal from the distal nail plate, and the proximal nail plate then is retracted using a clamp. The skin hook is used to retract the proximal nail fold to expose the pigment in the nail matrix, which is biopsied using the #15 blade and sent for histopathology. The proximal nail fold and retracted nail plate then are put back in place, and absorbable sutures are used to repair the defect. In certain cases, a 3-mm punch biopsy may be used to sample the nail plate and/or the surrounding soft tissue.

Practice Implications

A guide to surgical tools used during NB procedures, including less commonly encountered tools such as a nail elevator and English nail splitter, helps to close the educational gap of NB procedures among dermatology trainees and attending physicians. In conjunction with practical training with cadavers and models, a guide to surgical tools can be reviewed by trainees before hands-on exposure to nail surgery in a clinical setting. By increasing awareness of the tools needed to complete the procedure from start to finish, dermatologists may feel more prepared and confident in their ability to perform NBs, ultimately allowing for more rapid diagnosis of nail malignancies.

Practice Gap

The term nail biopsy (NB) may refer to a punch, excisional, shave, or longitudinal biopsy of the nail matrix and/or nail bed.¹ Nail surgeries, including NBs, are performed relatively infrequently. In a study using data from the Medicare Provider Utilization and Payment Database 2012-2017, only 1.01% of Mohs surgeons and 0.28% of general dermatologists in the United States performed NBs. Thirty-one states had no dermatologist-performed NBs, while 3 states had no nail biopsies performed by any physician, podiatrist, nurse practitioner, or physician assistant, indicating that there is a shortage of dermatology clinicians performing nail surgeries.²

Dermatologists may not be performing NBs due to unfamiliarity with nail unit anatomy and lack of formal NB training during residency.³ In a survey of 240 dermatology residents in the United States, 58% reported performing fewer than 10 nail procedures during residency, with 25% observing only.⁴ Of those surveyed, 1% had no exposure to nail procedures during 3 years of residency. Furthermore, when asked to assess their competency in nail surgery on a scale of not competent, competent, and very competent, approximately 30% responded that they were not competent.⁴ Without sufficient education on procedures involving the nail unit, residents may be reluctant to incorporate nail surgery into their clinical practice.

Due to their complexity, NBs require the use of several specialized surgical instruments that are not used for other dermatologic procedures, and residents and attending physicians who have limited nail training may be unfamiliar with these tools. To address this educational gap, we sought to create a guide that details the surgical instruments used for the nail matrix tangential excision (shave) biopsy technique—the most common technique used in our nail specialty clinic. This guide is intended for educational use by dermatologists who wish to incorporate NB as part of their practice.

Tools and Technique

As a major referral center, our New York City–based nail specialty clinic performs a large volume of NBs, many of them performed for clinically concerning longitudinal melanonychias for which a nail matrix shave biopsy most often is performed. We utilize a standardized tray consisting of 12 surgical instruments that are needed to successfully perform a NB from start to finish (Figure). In addition to standard surgical tray items, such as sutures and tissue scissors, additional specialized instruments are necessary for NB procedures, including a nail elevator, an English nail splitter, and skin hook.

After the initial incisions are made at 45° angles to the proximal nail fold surrounding the longitudinal band, the nail elevator is used to separate the proximal nail plate from the underlying nail bed. The English nail splitter is used to create a transverse split separating the proximal from the distal nail plate, and the proximal nail plate then is retracted using a clamp. The skin hook is used to retract the proximal nail fold to expose the pigment in the nail matrix, which is biopsied using the #15 blade and sent for histopathology. The proximal nail fold and retracted nail plate then are put back in place, and absorbable sutures are used to repair the defect. In certain cases, a 3-mm punch biopsy may be used to sample the nail plate and/or the surrounding soft tissue.

Practice Implications

A guide to surgical tools used during NB procedures, including less commonly encountered tools such as a nail elevator and English nail splitter, helps to close the educational gap of NB procedures among dermatology trainees and attending physicians. In conjunction with practical training with cadavers and models, a guide to surgical tools can be reviewed by trainees before hands-on exposure to nail surgery in a clinical setting. By increasing awareness of the tools needed to complete the procedure from start to finish, dermatologists may feel more prepared and confident in their ability to perform NBs, ultimately allowing for more rapid diagnosis of nail malignancies.

Psoriasis is a chronic inflammatory disease affecting approximately 8 million adults in the United States and 2% of the global population.^1,2 Psoriasis causes pain, itching, and disfigurement and is associated with a physical, psychological, and economic burden that substantially affects health-related quality of life.^3-5

Setting treatment goals and treating to target are evidence-based approaches that have been successfully applied to several chronic diseases to improve patient outcomes, including diabetes, hypertension, and rheumatoid arthritis.^6-9 Treat-to-target strategies generally set low disease activity (or remission) as an overall goal and seek to achieve this using available therapeutic options as necessary. Introduced following the availability of biologics and targeted systemic therapies, treat-to-target strategies generally provide guidance on expectations of treatment but not specific treatments, as personalized treatment decisions depend on an assessment of individual patients and consider clinical and demographic features as well as preferences for available therapeutic options. If targets are not achieved in the assigned time span, adjustments can be made to the treatment approach in close consultation with the patient. If the target is reached, follow-up visits can be scheduled to ensure improvement is maintained or to establish if more aggressive goals could be selected.

Treat-to-target strategies for the management of psoriasis developed by the National Psoriasis Foundation (NPF) Medical Board include reducing the extent of psoriasis to 1% or lower total body surface area (BSA) after 3 months of treatment.¹⁰ Treatment targets endorsed by the European Academy of Dermatology and Venereology (EADV) in guidelines on the use of systemic therapies in psoriasis include achieving a 75% or greater reduction in Psoriasis Area and Severity Index (PASI) score within 3 to 4 months of treatment.¹¹

In clinical practice, many patients do not achieve these treatment targets, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.^12,13 Moreover, conventional topical treatments (eg, topical corticosteroids) used by most patients with psoriasis regardless of disease severity are associated with adverse events that can limit their use. Most topical corticosteroids have US Food and Drug Administration label restrictions relating to sites of application, duration and extent of use, and frequency of administration.^14,15

Tapinarof cream 1% (VTAMA [Dermavant Sciences, Inc]) is a first-in-class topical nonsteroidal aryl hydrocarbon receptor agonist that was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults¹⁶ and is being studied for the treatment of plaque psoriasis in children 2 years and older as well as for atopic dermatitis in adults and children 2 years and older. In PSOARING 1 (ClinicalTrials .gov identifier NCT03956355) and PSOARING 2 (NCT03983980)—identical 12-week pivotal phase 3 trials—monotherapy with tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy vs vehicle cream and was well tolerated in adults with mild to severe plaque psoriasis (Supplementary Figure S1).¹⁷ Lebwohl et al¹⁷ reported that significantly higher PASI75 responses were observed at week 12 with tapinarof cream vs vehicle in PSOARING 1 and PSOARING 2 (36% and 48% vs 10% and 7%, respectively; both P<.0001). A significantly higher PASI90 response of 19% and 21% at week 12 also was observed with tapinarof cream vs 2% and 3% with vehicle in PSOARING 1 and PSOARING 2, respectively (P=.0005 and P<.0001).¹⁷

In PSOARING 3 (NCT04053387)—the long-term extension trial (Supplementary Figure S1)—efficacy continued to improve or was maintained beyond the two 12-week trials, with improvements in total BSA affected and PASI scores for up to 52 weeks.¹⁸ Tapinarof cream 1% QD demonstrated positive, rapid, and durable outcomes in PSOARING 3, including high rates of complete disease clearance (Physician Global Assessment [PGA] score=0 [clear])(40.9% [312/763]), durability of response on treatment with no evidence of tachyphylaxis, and a remittive effect of approximately 4 months when off therapy (defined as maintenance of a PGA score of 0 [clear] or 1 [almost clear] after first achieving a PGA score of 0).¹⁸

Herein, we report absolute treatment targets for patients with plaque psoriasis who received tapinarof cream 1% QD in the PSOARING trials that are at least as stringent as the corresponding NPF and EADV targets of achieving a total BSA affected of 1% or lower or a PASI75 response within 3 to 4 months, respectively.

METHODS

Study Design

The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.

Trial Participants

Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.^17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.

The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.

Trial Treatment

In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.

Outcome Measures and Statistical Analyses

The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.

Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.¹⁹ The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.

Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.

Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.

RESULTS

Baseline Patient Demographics and Disease Characteristics

The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m². The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).

Efficacy

Achievement of BSA-Affected Targets—The NPF-recommended target of 1% or lower total BSA affected within 3 months was achieved by 40% of patients (KM estimate [95% CI, 37%-43%])(Figure 1). Across the total trial period of up to 52 weeks, a total BSA affected of 1% or lower was achieved by 61% of patients (561/915), with the median time to target of approximately 4 months (KM estimate: 120 days [95% CI, 113-141])(Supplementary Figure S2a). Approximately 50% of patients (455/915) achieved a total BSA affected of 0.5% or lower, with a median time to target of 199 days (KM estimate [95% CI, 172-228)(Figure 1; Supplementary Figure S2b).

Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).

Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.^10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.

Safety

Safety data for the PSOARING trials have been previously reported.^17,18 The most common treatment-emergent adverse events were folliculitis, contact dermatitis, upper respiratory tract infection, and nasopharyngitis. Treatment-emergent adverse events generally were mild or moderate in severity and did not lead to trial discontinuation.^17,18

COMMENT

Treat-to-target management approaches aim to improve patient outcomes by striving to achieve optimal goals. The treat-to-target approach supports shared decision-making between clinicians and patients based on common expectations of what constitutes treatment success.

The findings of this analysis based on pooled data from a large cohort of patients demonstrate that a high proportion of patients can achieve or exceed recommended treatment targets with tapinarof cream 1% QD and maintain improvements long-term. The NPF-recommended treatment target of 1% or lower BSA affected within approximately 3 months (90 days) of treatment was achieved by 40% of tapinarof-treated patients. In addition, 1% or lower BSA affected at any time during the trials was achieved by 61% of patients (median, approximately 4 months). The analyses also indicated that PASI total scores of 3 or lower and 2 or lower were achieved by 75% and 67% of tapinarof-treated patients, respectively, within 2 to 3 months.

These findings support the previously reported efficacy of tapinarof cream, including high rates of complete disease clearance (40.9% [312/763]), durable response following treatment interruption, an off-therapy remittive effect of approximately 4 months, and good disease control on therapy with no evidence of tachyphylaxis.^17,18

CONCLUSION

Taken together with previously reported tapinarof efficacy and safety results, our findings demonstrate that a high proportion of patients treated with tapinarof cream as monotherapy can achieve aggressive treatment targets set by both US and European guidelines developed for systemic and biologic therapies. Tapinarof cream 1% QD is an effective topical treatment option for patients with plaque psoriasis that has been approved without restrictions relating to severity or extent of disease treated, duration of use, or application sites, including application to sensitive and intertriginous skin.

Acknowledgments—Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom (United Kingdom), and was funded by Dermavant Sciences, Inc, in accordance with Good Publication Practice (GPP) guidelines.

Psoriasis is a chronic inflammatory disease affecting approximately 8 million adults in the United States and 2% of the global population.^1,2 Psoriasis causes pain, itching, and disfigurement and is associated with a physical, psychological, and economic burden that substantially affects health-related quality of life.^3-5

Setting treatment goals and treating to target are evidence-based approaches that have been successfully applied to several chronic diseases to improve patient outcomes, including diabetes, hypertension, and rheumatoid arthritis.^6-9 Treat-to-target strategies generally set low disease activity (or remission) as an overall goal and seek to achieve this using available therapeutic options as necessary. Introduced following the availability of biologics and targeted systemic therapies, treat-to-target strategies generally provide guidance on expectations of treatment but not specific treatments, as personalized treatment decisions depend on an assessment of individual patients and consider clinical and demographic features as well as preferences for available therapeutic options. If targets are not achieved in the assigned time span, adjustments can be made to the treatment approach in close consultation with the patient. If the target is reached, follow-up visits can be scheduled to ensure improvement is maintained or to establish if more aggressive goals could be selected.

Treat-to-target strategies for the management of psoriasis developed by the National Psoriasis Foundation (NPF) Medical Board include reducing the extent of psoriasis to 1% or lower total body surface area (BSA) after 3 months of treatment.¹⁰ Treatment targets endorsed by the European Academy of Dermatology and Venereology (EADV) in guidelines on the use of systemic therapies in psoriasis include achieving a 75% or greater reduction in Psoriasis Area and Severity Index (PASI) score within 3 to 4 months of treatment.¹¹

In clinical practice, many patients do not achieve these treatment targets, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.^12,13 Moreover, conventional topical treatments (eg, topical corticosteroids) used by most patients with psoriasis regardless of disease severity are associated with adverse events that can limit their use. Most topical corticosteroids have US Food and Drug Administration label restrictions relating to sites of application, duration and extent of use, and frequency of administration.^14,15

Tapinarof cream 1% (VTAMA [Dermavant Sciences, Inc]) is a first-in-class topical nonsteroidal aryl hydrocarbon receptor agonist that was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults¹⁶ and is being studied for the treatment of plaque psoriasis in children 2 years and older as well as for atopic dermatitis in adults and children 2 years and older. In PSOARING 1 (ClinicalTrials .gov identifier NCT03956355) and PSOARING 2 (NCT03983980)—identical 12-week pivotal phase 3 trials—monotherapy with tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy vs vehicle cream and was well tolerated in adults with mild to severe plaque psoriasis (Supplementary Figure S1).¹⁷ Lebwohl et al¹⁷ reported that significantly higher PASI75 responses were observed at week 12 with tapinarof cream vs vehicle in PSOARING 1 and PSOARING 2 (36% and 48% vs 10% and 7%, respectively; both P<.0001). A significantly higher PASI90 response of 19% and 21% at week 12 also was observed with tapinarof cream vs 2% and 3% with vehicle in PSOARING 1 and PSOARING 2, respectively (P=.0005 and P<.0001).¹⁷

In PSOARING 3 (NCT04053387)—the long-term extension trial (Supplementary Figure S1)—efficacy continued to improve or was maintained beyond the two 12-week trials, with improvements in total BSA affected and PASI scores for up to 52 weeks.¹⁸ Tapinarof cream 1% QD demonstrated positive, rapid, and durable outcomes in PSOARING 3, including high rates of complete disease clearance (Physician Global Assessment [PGA] score=0 [clear])(40.9% [312/763]), durability of response on treatment with no evidence of tachyphylaxis, and a remittive effect of approximately 4 months when off therapy (defined as maintenance of a PGA score of 0 [clear] or 1 [almost clear] after first achieving a PGA score of 0).¹⁸

Herein, we report absolute treatment targets for patients with plaque psoriasis who received tapinarof cream 1% QD in the PSOARING trials that are at least as stringent as the corresponding NPF and EADV targets of achieving a total BSA affected of 1% or lower or a PASI75 response within 3 to 4 months, respectively.

METHODS

Study Design

The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.

Trial Participants

Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.^17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.

The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.

Trial Treatment

In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.

Outcome Measures and Statistical Analyses

The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.

Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.¹⁹ The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.

Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.

Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.

RESULTS

Baseline Patient Demographics and Disease Characteristics

The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m². The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).

Efficacy

Achievement of BSA-Affected Targets—The NPF-recommended target of 1% or lower total BSA affected within 3 months was achieved by 40% of patients (KM estimate [95% CI, 37%-43%])(Figure 1). Across the total trial period of up to 52 weeks, a total BSA affected of 1% or lower was achieved by 61% of patients (561/915), with the median time to target of approximately 4 months (KM estimate: 120 days [95% CI, 113-141])(Supplementary Figure S2a). Approximately 50% of patients (455/915) achieved a total BSA affected of 0.5% or lower, with a median time to target of 199 days (KM estimate [95% CI, 172-228)(Figure 1; Supplementary Figure S2b).

Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).

Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.^10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.

Safety

Safety data for the PSOARING trials have been previously reported.^17,18 The most common treatment-emergent adverse events were folliculitis, contact dermatitis, upper respiratory tract infection, and nasopharyngitis. Treatment-emergent adverse events generally were mild or moderate in severity and did not lead to trial discontinuation.^17,18

COMMENT

Treat-to-target management approaches aim to improve patient outcomes by striving to achieve optimal goals. The treat-to-target approach supports shared decision-making between clinicians and patients based on common expectations of what constitutes treatment success.

The findings of this analysis based on pooled data from a large cohort of patients demonstrate that a high proportion of patients can achieve or exceed recommended treatment targets with tapinarof cream 1% QD and maintain improvements long-term. The NPF-recommended treatment target of 1% or lower BSA affected within approximately 3 months (90 days) of treatment was achieved by 40% of tapinarof-treated patients. In addition, 1% or lower BSA affected at any time during the trials was achieved by 61% of patients (median, approximately 4 months). The analyses also indicated that PASI total scores of 3 or lower and 2 or lower were achieved by 75% and 67% of tapinarof-treated patients, respectively, within 2 to 3 months.

These findings support the previously reported efficacy of tapinarof cream, including high rates of complete disease clearance (40.9% [312/763]), durable response following treatment interruption, an off-therapy remittive effect of approximately 4 months, and good disease control on therapy with no evidence of tachyphylaxis.^17,18

CONCLUSION

Taken together with previously reported tapinarof efficacy and safety results, our findings demonstrate that a high proportion of patients treated with tapinarof cream as monotherapy can achieve aggressive treatment targets set by both US and European guidelines developed for systemic and biologic therapies. Tapinarof cream 1% QD is an effective topical treatment option for patients with plaque psoriasis that has been approved without restrictions relating to severity or extent of disease treated, duration of use, or application sites, including application to sensitive and intertriginous skin.

Acknowledgments—Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom (United Kingdom), and was funded by Dermavant Sciences, Inc, in accordance with Good Publication Practice (GPP) guidelines.

Psoriasis is a chronic inflammatory disease affecting approximately 8 million adults in the United States and 2% of the global population.^1,2 Psoriasis causes pain, itching, and disfigurement and is associated with a physical, psychological, and economic burden that substantially affects health-related quality of life.^3-5

Setting treatment goals and treating to target are evidence-based approaches that have been successfully applied to several chronic diseases to improve patient outcomes, including diabetes, hypertension, and rheumatoid arthritis.^6-9 Treat-to-target strategies generally set low disease activity (or remission) as an overall goal and seek to achieve this using available therapeutic options as necessary. Introduced following the availability of biologics and targeted systemic therapies, treat-to-target strategies generally provide guidance on expectations of treatment but not specific treatments, as personalized treatment decisions depend on an assessment of individual patients and consider clinical and demographic features as well as preferences for available therapeutic options. If targets are not achieved in the assigned time span, adjustments can be made to the treatment approach in close consultation with the patient. If the target is reached, follow-up visits can be scheduled to ensure improvement is maintained or to establish if more aggressive goals could be selected.

Treat-to-target strategies for the management of psoriasis developed by the National Psoriasis Foundation (NPF) Medical Board include reducing the extent of psoriasis to 1% or lower total body surface area (BSA) after 3 months of treatment.¹⁰ Treatment targets endorsed by the European Academy of Dermatology and Venereology (EADV) in guidelines on the use of systemic therapies in psoriasis include achieving a 75% or greater reduction in Psoriasis Area and Severity Index (PASI) score within 3 to 4 months of treatment.¹¹

In clinical practice, many patients do not achieve these treatment targets, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.^12,13 Moreover, conventional topical treatments (eg, topical corticosteroids) used by most patients with psoriasis regardless of disease severity are associated with adverse events that can limit their use. Most topical corticosteroids have US Food and Drug Administration label restrictions relating to sites of application, duration and extent of use, and frequency of administration.^14,15

Tapinarof cream 1% (VTAMA [Dermavant Sciences, Inc]) is a first-in-class topical nonsteroidal aryl hydrocarbon receptor agonist that was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults¹⁶ and is being studied for the treatment of plaque psoriasis in children 2 years and older as well as for atopic dermatitis in adults and children 2 years and older. In PSOARING 1 (ClinicalTrials .gov identifier NCT03956355) and PSOARING 2 (NCT03983980)—identical 12-week pivotal phase 3 trials—monotherapy with tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy vs vehicle cream and was well tolerated in adults with mild to severe plaque psoriasis (Supplementary Figure S1).¹⁷ Lebwohl et al¹⁷ reported that significantly higher PASI75 responses were observed at week 12 with tapinarof cream vs vehicle in PSOARING 1 and PSOARING 2 (36% and 48% vs 10% and 7%, respectively; both P<.0001). A significantly higher PASI90 response of 19% and 21% at week 12 also was observed with tapinarof cream vs 2% and 3% with vehicle in PSOARING 1 and PSOARING 2, respectively (P=.0005 and P<.0001).¹⁷

In PSOARING 3 (NCT04053387)—the long-term extension trial (Supplementary Figure S1)—efficacy continued to improve or was maintained beyond the two 12-week trials, with improvements in total BSA affected and PASI scores for up to 52 weeks.¹⁸ Tapinarof cream 1% QD demonstrated positive, rapid, and durable outcomes in PSOARING 3, including high rates of complete disease clearance (Physician Global Assessment [PGA] score=0 [clear])(40.9% [312/763]), durability of response on treatment with no evidence of tachyphylaxis, and a remittive effect of approximately 4 months when off therapy (defined as maintenance of a PGA score of 0 [clear] or 1 [almost clear] after first achieving a PGA score of 0).¹⁸

Herein, we report absolute treatment targets for patients with plaque psoriasis who received tapinarof cream 1% QD in the PSOARING trials that are at least as stringent as the corresponding NPF and EADV targets of achieving a total BSA affected of 1% or lower or a PASI75 response within 3 to 4 months, respectively.

METHODS

Study Design

The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.

Trial Participants

Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.^17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.

The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.

Trial Treatment

In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.

Outcome Measures and Statistical Analyses

The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.

Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.¹⁹ The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.

Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.

Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.

RESULTS

Baseline Patient Demographics and Disease Characteristics

The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m². The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).

Efficacy

Achievement of BSA-Affected Targets—The NPF-recommended target of 1% or lower total BSA affected within 3 months was achieved by 40% of patients (KM estimate [95% CI, 37%-43%])(Figure 1). Across the total trial period of up to 52 weeks, a total BSA affected of 1% or lower was achieved by 61% of patients (561/915), with the median time to target of approximately 4 months (KM estimate: 120 days [95% CI, 113-141])(Supplementary Figure S2a). Approximately 50% of patients (455/915) achieved a total BSA affected of 0.5% or lower, with a median time to target of 199 days (KM estimate [95% CI, 172-228)(Figure 1; Supplementary Figure S2b).

Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).

Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.^10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.

Safety

Safety data for the PSOARING trials have been previously reported.^17,18 The most common treatment-emergent adverse events were folliculitis, contact dermatitis, upper respiratory tract infection, and nasopharyngitis. Treatment-emergent adverse events generally were mild or moderate in severity and did not lead to trial discontinuation.^17,18

COMMENT

Treat-to-target management approaches aim to improve patient outcomes by striving to achieve optimal goals. The treat-to-target approach supports shared decision-making between clinicians and patients based on common expectations of what constitutes treatment success.

The findings of this analysis based on pooled data from a large cohort of patients demonstrate that a high proportion of patients can achieve or exceed recommended treatment targets with tapinarof cream 1% QD and maintain improvements long-term. The NPF-recommended treatment target of 1% or lower BSA affected within approximately 3 months (90 days) of treatment was achieved by 40% of tapinarof-treated patients. In addition, 1% or lower BSA affected at any time during the trials was achieved by 61% of patients (median, approximately 4 months). The analyses also indicated that PASI total scores of 3 or lower and 2 or lower were achieved by 75% and 67% of tapinarof-treated patients, respectively, within 2 to 3 months.

These findings support the previously reported efficacy of tapinarof cream, including high rates of complete disease clearance (40.9% [312/763]), durable response following treatment interruption, an off-therapy remittive effect of approximately 4 months, and good disease control on therapy with no evidence of tachyphylaxis.^17,18

CONCLUSION

Taken together with previously reported tapinarof efficacy and safety results, our findings demonstrate that a high proportion of patients treated with tapinarof cream as monotherapy can achieve aggressive treatment targets set by both US and European guidelines developed for systemic and biologic therapies. Tapinarof cream 1% QD is an effective topical treatment option for patients with plaque psoriasis that has been approved without restrictions relating to severity or extent of disease treated, duration of use, or application sites, including application to sensitive and intertriginous skin.

Acknowledgments—Editorial and medical writing support under the guidance of the authors was provided by Melanie Govender, MSc (Med), ApotheCom (United Kingdom), and was funded by Dermavant Sciences, Inc, in accordance with Good Publication Practice (GPP) guidelines.

The Diagnosis: Nevus Sebaceus of Jadassohn

The diagnosis of nevus sebaceus of Jadassohn was made clinically based on the lesion’s appearance and presence since birth as well as the absence of systemic symptoms. Clinically, nevus sebaceus of Jadassohn typically manifests as a well-demarcated, yellow- brown plaque often located on the scalp, as was seen in our patient. The lack of pruritus and pain further supported the diagnosis in our patient. No biopsy was performed, as the presentation was considered classic for this condition. Our patient opted to forgo surgery and will be routinely monitored for any changes, as nevus sebaceus has a potential risk, albeit low, for malignant transformation later in life. No changes have been observed since the initial presentation, and regular follow-ups are planned to monitor for future developments.

Nevus sebaceus of Jadassohn is a hamartomatous lesion involving the pilosebaceous follicle and adjacent adnexal structures.^1-3 It most commonly forms on the scalp (59.3%) and is accompanied by partial or total alopecia. ^3,4 It is seen less often on the face, periauricular area, or neck^1,4; thorax or limbs⁵; and oral or genital mucosae.⁶ Nevus sebaceus of Jadassohn affects approximately 0.3% of newborns,¹ usually as a solitary lesion that can form an extensive plaque. The male-to-female occurrence ratio has been reported as equal to slightly more predominant in females; all races and ethnicities are affected.^1,5

Nevus sebaceus of Jadassohn follows 3 stages of clinical development: infantile, adolescent, and adulthood. It manifests at birth or shortly afterward as a smooth hairless patch or plaque that is yellowish and can be hyperpigmented in Black patients.⁵ It may have an oval or linear configuration, typically is asymptomatic, and often arises along the Blaschko lines when it occurs as multiple lesions (a rare manifestation).¹ During puberty, hormonal changes cause accelerated growth, sebaceous gland maturation, and epidermal hyperplasia. ⁷ Nevus sebaceus of Jadassohn often is not identified until this stage, when its classic wartlike appearance has fully developed.¹

Patients with nevus sebaceus of Jadassohn have a 10% to 20% risk for tumor development in adulthood.^2,7 Trichoblastoma and syringocystadenoma papilliferum are the most frequently described neoplasms.⁸ Basal cell carcinoma is the most common malignant secondary neoplasm with an occurrence rate of 0.8%.^6,9 However, basal cell carcinoma and trichoblastoma may share histopathologic features, which may lead to misdiagnosis and a higher reported incidence of basal cell carcinoma in adults than is accurate.²

Early prophylactic surgical removal of nevus sebaceus of Jadassohn has been recommended; however, surgical management is controversial because the risk for a benign secondary neoplasm remains relatively high while the risk for malignancy is much lower.^2,7 Surgical excision remains an acceptable option once the patient is mature enough to tolerate the procedure.¹ However, patient education regarding watchful waiting vs a surgical approach— and the risks of each—is critical to ensure shared decision-making and a management plan tailored to the individual.

The differential diagnosis includes hypertrophic lichen planus, Langerhans cell histiocytosis (Letterer-Siwe disease type), epidermal nevus, and seborrheic keratosis. Hypertrophic lichen planus often occurs symmetrically on the dorsal feet and shins with thick, scaly, and extremely pruritic plaques. The lesions often persist for an average of 6 years and may lead to multiple keratoacanthomas or follicular base squamous cell carcinomas. Langerhans cell histiocytosis (Letterer-Siwe disease type) manifests with acute, disseminated, visceral, and cutaneous lesions before 2 years of age. These lesions appear as 1- to 2-mm, pink, seborrheic papules, pustules, or vesicles on the scalp, flexural neck, axilla, perineum, and trunk; they often are associated with petechiae, purpura, scale, crust, erosion, impetiginization, and tender fissures. Epidermal nevus occurs within the first year of life and is a hamartoma of the epidermis and papillary dermis. It manifests as papillomatous pigmented linear lines along the Blaschko lines. Seborrheic keratosis manifests as well-demarcated, waxy/verrucous, brown papules with a “stuck on” appearance on hair-bearing skin sparing the mucosae. They are common benign lesions associated with sun exposure and often manifest in the fourth decade of life.¹⁰

The Diagnosis: Nevus Sebaceus of Jadassohn

The diagnosis of nevus sebaceus of Jadassohn was made clinically based on the lesion’s appearance and presence since birth as well as the absence of systemic symptoms. Clinically, nevus sebaceus of Jadassohn typically manifests as a well-demarcated, yellow- brown plaque often located on the scalp, as was seen in our patient. The lack of pruritus and pain further supported the diagnosis in our patient. No biopsy was performed, as the presentation was considered classic for this condition. Our patient opted to forgo surgery and will be routinely monitored for any changes, as nevus sebaceus has a potential risk, albeit low, for malignant transformation later in life. No changes have been observed since the initial presentation, and regular follow-ups are planned to monitor for future developments.

Nevus sebaceus of Jadassohn is a hamartomatous lesion involving the pilosebaceous follicle and adjacent adnexal structures.^1-3 It most commonly forms on the scalp (59.3%) and is accompanied by partial or total alopecia. ^3,4 It is seen less often on the face, periauricular area, or neck^1,4; thorax or limbs⁵; and oral or genital mucosae.⁶ Nevus sebaceus of Jadassohn affects approximately 0.3% of newborns,¹ usually as a solitary lesion that can form an extensive plaque. The male-to-female occurrence ratio has been reported as equal to slightly more predominant in females; all races and ethnicities are affected.^1,5

Nevus sebaceus of Jadassohn follows 3 stages of clinical development: infantile, adolescent, and adulthood. It manifests at birth or shortly afterward as a smooth hairless patch or plaque that is yellowish and can be hyperpigmented in Black patients.⁵ It may have an oval or linear configuration, typically is asymptomatic, and often arises along the Blaschko lines when it occurs as multiple lesions (a rare manifestation).¹ During puberty, hormonal changes cause accelerated growth, sebaceous gland maturation, and epidermal hyperplasia. ⁷ Nevus sebaceus of Jadassohn often is not identified until this stage, when its classic wartlike appearance has fully developed.¹

Patients with nevus sebaceus of Jadassohn have a 10% to 20% risk for tumor development in adulthood.^2,7 Trichoblastoma and syringocystadenoma papilliferum are the most frequently described neoplasms.⁸ Basal cell carcinoma is the most common malignant secondary neoplasm with an occurrence rate of 0.8%.^6,9 However, basal cell carcinoma and trichoblastoma may share histopathologic features, which may lead to misdiagnosis and a higher reported incidence of basal cell carcinoma in adults than is accurate.²

Early prophylactic surgical removal of nevus sebaceus of Jadassohn has been recommended; however, surgical management is controversial because the risk for a benign secondary neoplasm remains relatively high while the risk for malignancy is much lower.^2,7 Surgical excision remains an acceptable option once the patient is mature enough to tolerate the procedure.¹ However, patient education regarding watchful waiting vs a surgical approach— and the risks of each—is critical to ensure shared decision-making and a management plan tailored to the individual.

The differential diagnosis includes hypertrophic lichen planus, Langerhans cell histiocytosis (Letterer-Siwe disease type), epidermal nevus, and seborrheic keratosis. Hypertrophic lichen planus often occurs symmetrically on the dorsal feet and shins with thick, scaly, and extremely pruritic plaques. The lesions often persist for an average of 6 years and may lead to multiple keratoacanthomas or follicular base squamous cell carcinomas. Langerhans cell histiocytosis (Letterer-Siwe disease type) manifests with acute, disseminated, visceral, and cutaneous lesions before 2 years of age. These lesions appear as 1- to 2-mm, pink, seborrheic papules, pustules, or vesicles on the scalp, flexural neck, axilla, perineum, and trunk; they often are associated with petechiae, purpura, scale, crust, erosion, impetiginization, and tender fissures. Epidermal nevus occurs within the first year of life and is a hamartoma of the epidermis and papillary dermis. It manifests as papillomatous pigmented linear lines along the Blaschko lines. Seborrheic keratosis manifests as well-demarcated, waxy/verrucous, brown papules with a “stuck on” appearance on hair-bearing skin sparing the mucosae. They are common benign lesions associated with sun exposure and often manifest in the fourth decade of life.¹⁰

The Diagnosis: Nevus Sebaceus of Jadassohn

The diagnosis of nevus sebaceus of Jadassohn was made clinically based on the lesion’s appearance and presence since birth as well as the absence of systemic symptoms. Clinically, nevus sebaceus of Jadassohn typically manifests as a well-demarcated, yellow- brown plaque often located on the scalp, as was seen in our patient. The lack of pruritus and pain further supported the diagnosis in our patient. No biopsy was performed, as the presentation was considered classic for this condition. Our patient opted to forgo surgery and will be routinely monitored for any changes, as nevus sebaceus has a potential risk, albeit low, for malignant transformation later in life. No changes have been observed since the initial presentation, and regular follow-ups are planned to monitor for future developments.

Nevus sebaceus of Jadassohn is a hamartomatous lesion involving the pilosebaceous follicle and adjacent adnexal structures.^1-3 It most commonly forms on the scalp (59.3%) and is accompanied by partial or total alopecia. ^3,4 It is seen less often on the face, periauricular area, or neck^1,4; thorax or limbs⁵; and oral or genital mucosae.⁶ Nevus sebaceus of Jadassohn affects approximately 0.3% of newborns,¹ usually as a solitary lesion that can form an extensive plaque. The male-to-female occurrence ratio has been reported as equal to slightly more predominant in females; all races and ethnicities are affected.^1,5

Nevus sebaceus of Jadassohn follows 3 stages of clinical development: infantile, adolescent, and adulthood. It manifests at birth or shortly afterward as a smooth hairless patch or plaque that is yellowish and can be hyperpigmented in Black patients.⁵ It may have an oval or linear configuration, typically is asymptomatic, and often arises along the Blaschko lines when it occurs as multiple lesions (a rare manifestation).¹ During puberty, hormonal changes cause accelerated growth, sebaceous gland maturation, and epidermal hyperplasia. ⁷ Nevus sebaceus of Jadassohn often is not identified until this stage, when its classic wartlike appearance has fully developed.¹

Patients with nevus sebaceus of Jadassohn have a 10% to 20% risk for tumor development in adulthood.^2,7 Trichoblastoma and syringocystadenoma papilliferum are the most frequently described neoplasms.⁸ Basal cell carcinoma is the most common malignant secondary neoplasm with an occurrence rate of 0.8%.^6,9 However, basal cell carcinoma and trichoblastoma may share histopathologic features, which may lead to misdiagnosis and a higher reported incidence of basal cell carcinoma in adults than is accurate.²

Early prophylactic surgical removal of nevus sebaceus of Jadassohn has been recommended; however, surgical management is controversial because the risk for a benign secondary neoplasm remains relatively high while the risk for malignancy is much lower.^2,7 Surgical excision remains an acceptable option once the patient is mature enough to tolerate the procedure.¹ However, patient education regarding watchful waiting vs a surgical approach— and the risks of each—is critical to ensure shared decision-making and a management plan tailored to the individual.

The differential diagnosis includes hypertrophic lichen planus, Langerhans cell histiocytosis (Letterer-Siwe disease type), epidermal nevus, and seborrheic keratosis. Hypertrophic lichen planus often occurs symmetrically on the dorsal feet and shins with thick, scaly, and extremely pruritic plaques. The lesions often persist for an average of 6 years and may lead to multiple keratoacanthomas or follicular base squamous cell carcinomas. Langerhans cell histiocytosis (Letterer-Siwe disease type) manifests with acute, disseminated, visceral, and cutaneous lesions before 2 years of age. These lesions appear as 1- to 2-mm, pink, seborrheic papules, pustules, or vesicles on the scalp, flexural neck, axilla, perineum, and trunk; they often are associated with petechiae, purpura, scale, crust, erosion, impetiginization, and tender fissures. Epidermal nevus occurs within the first year of life and is a hamartoma of the epidermis and papillary dermis. It manifests as papillomatous pigmented linear lines along the Blaschko lines. Seborrheic keratosis manifests as well-demarcated, waxy/verrucous, brown papules with a “stuck on” appearance on hair-bearing skin sparing the mucosae. They are common benign lesions associated with sun exposure and often manifest in the fourth decade of life.¹⁰