MDedge Dermatology

Cosmetic laser procedures as well as energy-based fat reduction and body-contouring devices are increasingly popular among individuals with skin of color (SOC). Innovations in cosmetic devices and procedures tailored for SOC have allowed for the optimization of outcomes in this patient population. In this article, SOC is defined as darker skin types, including Fitzpatrick skin types (FSTs) IV to VI and ethnic backgrounds such as LatinX, African American, Southeast Asian, Native American, Pacific Islander, Middle Eastern, Asian, and African. Indications for laser treatment include dermatosis papulosa nigrans (DPN), acne scars, skin rejuvenation, and hyperpigmentation. There currently are 6 procedures for nonsurgical fat reduction that are approved by the US Food and Drug Administration (FDA): high-frequency focused ultrasound, cryolipolysis, laser lipolysis, injection lipolysis, radiofrequency lipolysis, and magnetic resonance contouring (Supplementary Table S1).¹

In this review, our initial focus is cosmetic laser ­procedures, encompassing FDA-cleared indications along with the associated risks and benefits in SOC populations. Subsequently, we delve into the realms of energy-based fat reduction and body contouring, offering a comprehensive overview of these noninvasive therapies and addressing considerations for efficacy and safety in these patients.

Dermatosis Papulosa Nigra

In patients with SOC, scissor excision, curettage, or electrodesiccation are the mainstay treatments for removal of DPN (Figure 1). Curettage and electrodesiccation can cause temporary postinflammatory hyperpigmentation (PIH) in these populations, while cryotherapy is not a preferred method in patients with SOC due to the possibility of cryotherapy-induced depigmentation. In a 14-patient split-face study comparing the 532-nm potassium titanyl phosphate (KTP) laser vs electrodesiccation in FSTs IV to VI, the KTP-treated side showed an improvement rate of 96%, while the electrodesiccation side showed an improvement rate of 79%. There was a statistically significant favorable experience for KTP with regard to pain tolerability (P=.002).² Complete resolution of lesions may be seen after 3 to 4 sessions at 4-week intervals. Additionally, the 1064-nm Nd:YAG laser was assessed for treatment of DPN in 2 patients, with 70% to 90% of lesions resolved after a single treatment with no complications.³

Most dermatologists still rely on curettage and electrodesiccation instead of laser therapy to remove DPNs in patients with SOC. The use of the Nd:YAG laser is promising yet expensive for the provider both to purchase and maintain. Electrodesiccation has been used by dermatology practices for decades and can be used without permanent discoloration. To minimize the risk for PIH, we recommend application of a healing ointment such as petroleum jelly or aloe vera gel to the treated lesions as well as lightening agents for PIH and daily use of sunscreen. Overall, providers do not need to purchase an expensive laser device for DPN removal.

Acne Scars

The invention of fractional technology in the early 2000s and its favorable safety profile have changed how dermatologists treat scarring in patients with SOC.^4,5 In fact, nonablative fractional (NAF) resurfacing is a preferred treatment modality for management of acne scars in patients with SOC.⁶ In one study of the 1550-nm erbium-doped fiber laser for treatment of acne scars (3 treatments at intervals of 2-3 weeks) in 10 Japanese patients, clinical improvement was seen in all patients and no severe adverse effects were reported.⁷ In another study, 27 Korean patients with FSTs IV and V were treated with an NAF resurfacing device for acne scars. Excellent results were reported in 30% (8/27) of patients, substantial improvement in 59% (16/27), and moderate improvement in 11% (3/27).⁸ To evaluate outcomes in patients treated with NAF resurfacing, a retrospective review of 961 treatments showed a hyperpigmentation rate of 11.6% in those with FST IV and 33% in FST V.⁹

In one study of the short-pulsed nonablative Nd:YAG laser, 9 patients with FSTs I to V and 2 patients with FSTs IV to V underwent 8 treatments at 2-week intervals. Three blinded observers found a 29% improvement in the Global Acne Scar Severity score, while 89% (8/9) of patients self-reported subjective improvement in their acne scars.¹⁰

The 755-nm picosecond laser and diffractive lens array also have been shown to reduce the appearance of acne scars in patients with SOC, as shown via serial photography in a retrospective study of 56 patients with FSTs IV to VI. Transient hyperpigmentation, erythema, and edema were reported.¹¹

Nonablative laser therapy is preferred for skin rejuvenation in patients with SOC due to a reduced risk for postprocedural hyperpigmentation.¹¹ Ablative resurfacing (eg, CO₂ laser) poses major risks for postprocedural hyperpigmentation, hypopigmentation, and scar formation and therefore should be avoided in these populations.^12,13 A study involving 30 Asian patients (FSTs III-IV) demonstrated that the 1550-nm fractional laser was well tolerated, though higher treatment densities and fluences may lead to temporary adverse effects such as increased redness, swelling, and pain (P<.01).¹⁴ Furthermore, greater density was shown to cause higher levels of redness, hyperpigmentation, and swelling in comparison to higher fluence settings. Of note, patient satisfaction was markedly higher in patients who underwent treatment with higher fluence settings but not in patients with higher densities (P<.05). Postprocedural hyperpigmentation was noted in 6.7% (2/30) of patients studied.¹⁴ In another study, 8 patients with FSTs II to V were treated with either the 1064-nm long-pulsed Nd:YAG laser or the grid fractional monopolar radiofrequency laser.¹⁵ All participants experienced a significant decrease in mean wrinkle count using the Lemperle wrinkle assessment (P<.05). A significant decrease in mean wrinkle assessment score from 3.5 to 3.17 in clinical assessment and a decrease from 3.165 to 2.33 for photographic assessment was noted in patients treated with the grid laser (P<.05). A similar decrease in mean wrinkle assessment score was observed in the Nd:YAG group, with a mean decrease of 3.665 to 2.83 after 2 months for clinical assessment and 3.5 to 2.67 for photographic assessment. Among all patients in the study, 68% (6/8) experienced erythema, 25% (2/8) had a burning sensation, and 25% (2/8) experienced urticaria immediately postprocedure.¹⁵

Nonablative fractional resurfacing is preferred for the management of acne scars in patients with SOC. Adverse effects such as hyperpigmentation typically are transient, and the risk may be minimized with strict photoprotective practices following the procedure. Furthermore, avoidance of topicals containing exfoliants or α-hydroxy acids applied to the treated area following the procedure also may mitigate the risk for postprocedural hyperpigmentation.¹⁶ If hyperpigmentation does occur, use of topical melanogenesis inhibitors such as hydroquinone, kojic acid, or azelaic acid has shown some utility in practice.

Skin Rejuvenation

Nonablative fractional lasers (NAFLs) continue to be popular for treatment of photoaging. One study including 10 Asian patients (FSTs III-V) assessed the 1440-nm diode-based fractional laser for facial rejuvenation.¹⁷ After 4 sessions at 2-week intervals, 80% (8/10) of patients reported decreased skin roughness after both the second and third treatments, while 90% (9/10) had improved texture 1 month after the final procedure. Adverse effects included moderate facial edema and one case of transient hyperpigmentation.¹⁷ Another study reported a significant reduction in pore score (P<.002), with patients noting an overall improvement in skin appearance with minimal erythema, dryness, and flaking following 6 sessions at 2-week intervals using the 1440-nm diode-based fractional laser.¹⁸

The 1550-nm diode fractional laser significantly improved skin pigmentation (P<.001) and texture (P<.001) in 10 patients with FSTs II to IV following 5 sessions at 2- to 3-week intervals, with self-resolving erythema and edema posttreatment (Supplementary Table S2).¹⁹ Overall, NAFLs for the treatment of photoaging are effective with minimal adverse effects (eg, facial edema), which can be reduced with application of cold compression to the face and elevation of the head following treatment as well as the use of additional pillows during overnight sleep.

Laser Treatment for Hyperpigmentation Disorders

Melasma—The FDA recently approved fractional photothermolysis for the treatment of melasma; however, due to the risk for hyperpigmentation given its pathogenesis linked to hyperactive melanocytes, this laser is not considered a first-line therapy for melasma.²⁰ In a split-face, randomized study, 22 patients with FSTs III to V who were diagnosed with either dermal or mixed-type melasma were treated with a low-fluence Q-switched Nd:YAG laser combined with hydroquinone 2% vs hydroquinone 2% alone (Supplementary Table S3).²¹ Each patient was treated weekly for 5 consecutive weeks. The laser-treated side was found to reach an average of 92.5% improvement compared with 19.7% on the hydroquinone-only side. Three of the 22 (13.6%) patients developed mottled hypopigmentation after 5 laser treatments, and 8 (36.4%) developed confetti-type hypopigmentation. Four (18.2%) patients developed rebound hyperpigmentation, and all 22 patients experienced recurrence of melasma by 12 weeks posttreatment.²¹

First-line treatment for melasma involves the application of topical lightening agents such as hydroquinone, azelaic acid, kojic acid, retinoids, or mild topical steroids. Combining laser technology with topical medications can enhance treatment outcomes, particularly yielding positive results for patients with persistent pigmentation concerns. Notably, utilization of 650-microsecond technology with the 1064-nm Nd:YAG laser is considered superior in clinical practice, especially for patients with FSTs IV through VI.

Postinflammatory Hyperpigmentation—A retrospective evaluation of 61 patients with FSTs IV to VI with PIH treated with a 1927-nm NAFL showed a mean improvement of 43.24%, as assessed by 2 dermatologists.²² Additionally, the Nd:YAG 1064-nm 650-microsecond pulse duration laser is an emerging treatment that delivers high and low fluences between 4 J/cm² and 255 J/cm² within a single 650-microsecond pulse duration.²³ The short-pulse duration avoids overheating the skin, mitigating procedural discomfort and the risk for adverse effects commonly seen with the previous generation of low-pulsed lasers. In addition to PIH, this laser has been successfully used to treat pseudofolliculitis barbae.²⁴

Solar Lentigos—In a split-face study treating solar lentigos in Asian patients, 4 treatments with a low-pulsed KTP 532-nm laser were administered with and without a second treatment with a low-pulsed 1064-nm Nd:YAG laser.²⁵ Scoring of a modified pigment severity index and measurement of the melanin index showed that skin treated with the low-pulsed 532-nm laser alone and in combination with the low-pulsed 1064-nm Nd:YAG laser resulted in improvement at 3 months’ follow-up. However, there was no difference between the 2 sides of the face, leading the researchers to conclude that the low-pulsed 532-nm laser appears to be safe and effective for treatment of solar lentigos in Asian patients and does not require the addition of the low-pulsed 1064-nm laser.²⁵  

To avoid hyperpigmentation in patients with SOC, strict photoprotection to the treated areas should be advised. Proper cooling of the laser-treated area is required to minimize PIH, as cooling decreases tissue damage and excessive thermal injury. Test spots should be considered prior to initiation of the full laser treatment. Hydroquinone in a 4% concentration applied daily for 2 weeks preprocedure commonly is employed to reduce the risk for postprocedural hyperpigmentation in clinical practice.^26,27

Skin Tightening and Body Contouring

In general, skin-tightening and body-contouring devices are among the most sought-after procedures. Studies performed in patients with SOC are limited. Herein, we provide background on why these devices are favorable for patients with SOC and our experiences in using them. A summary of these devices can be found in Supplementary Table S4.

Radiofrequency Skin Tightening—Radiofrequency devices are utilized for skin tightening as well as mild fat reduction; they commonly are used on the abdomen, thighs, buttocks, and face.²⁸ People with SOC are more responsive to radiofrequency skin-tightening therapy due to higher baseline collagen content and dermal thickness, more sebaceous activity and skin elasticity, and more melanin content which offers protective thermal buffering.^29,30 As the radiofrequency device emits heat, penetrating deep into the dermis, it generates collagen remodeling and synthesis within 4 to 6 months posttreatment.

Nonsurgical Fat Reduction

Procedures for nonsurgical fat reduction are favorable due to minimal recovery time, manageable cost, and an in-office procedure setting. As noted previously, there are 6 FDA-indicated interventions for nonsurgical fat reduction: ultrasonography, cryolipolysis, laser lipolysis, injection lipolysis, radiofrequency lipolysis, and magnetic resonance contouring.³¹

Ultrasonography—Ultrasound devices designed for body contouring are used for skin tightening and mild fat reduction through the use of acoustic energy.³² These devices can be divided into 2 categories: high frequency and low frequency, with the high-frequency devices being the most popular. High-frequency ultrasound energy produces heat at target sites, which induces necrosis of adipocytes and stimulates collagen remodeling within the tissue matrix.³³ Tissue temperatures above 56°C stimulate adipocyte necrosis while sparing nearby nerves and vessels.²⁸ Because of the short duration of the procedure, the risk for epidermal damage is minimal. Contrary to high-frequency ultrasonography, focus-pulsed ultrasonography employs low-frequency waves to induce the mechanical disruption of adipocytes, which is generally better tolerated due to its nonthermal mechanism. The latter may be advantageous in patients with SOC due to a reduced risk for thermal injury to the epidermis. Multiple treatments often are needed at 3- to 4-week intervals, resulting in gradual improvement observed over 2 to 6 months. One study of microfocused ultrasonography in 25 Asian patients for treatment of face and neck laxity reported that skin laxity was improved or much improved in 84% (21/25) of patients following treatment.³⁴ Adverse effects were reported as mild and transient, resolving within 90 days.³⁴ Ultrasound devices also were shown to improve wrinkles, texture, and overall appearance of the skin in a 71-year-old African American woman 4 months following treatment (Figure 2). These photographs highlight the clinical utility of a microfocused ultrasound skin-tightening treatment in African American patients.

Cryolipolysis—Cryolipolysis is a noninvasive body contouring procedure that employs controlled cooling to induce subcutaneous panniculitis. Through cold-induced apoptosis of adipocytes, this procedure selectively reduces adipose tissue in localized areas such as the flank, abdomen, thighs, buttocks, back, submental area, and upper arms. The temperature used in cryolipolysis is approximately –10°C.³⁵ The lethal temperature for melanocytes is –4 °C, below which melanocyte apoptosis may be induced, resulting in depigmentation. Given the prolonged contact of the skin with a cryolipolysis device for up to 60 minutes during a body-contouring procedure, there is a risk for resultant depigmentation in darker skin types. Controlled studies are needed to fully evaluate the safety and efficacy of cryolipolysis in patients with SOC. One retrospective study of cryolipolysis applied to the abdomen and upper arm of 4122 Asian patients reported a significant (P<.05) reduction in the circumference of the abdomen and the upper-arm areas. No long-term adverse effects were reported.³⁶

Laser Lipolysis—The 1060-nm diode laser for body contouring selectively destroys adipose tissue, resulting in body contouring via thermally induced inflammation. Hyperthermic exposure for 15 minutes selectively elevates adipocyte temperature between 42°C to 47°C, which triggers apoptosis and the eventual clearance of destroyed cells from the interstitial space.³⁷ The selectivity of the 1060-nm wavelength coupled with the device’s contact cooling system preserves the overlying skin and adnexa during the procedure,³⁷ which would minimize epidermal damage that may induce dyspigmentation in patients with SOC. No notable adverse effects or dyspigmentation have been reported using this device.

Injection Lipolysis—Deoxycholic acid is an injectable adipocytolytic for the reduction of submental fat. It nonselectively lyses muscle and other adjacent nonfatty tissue. One study of 50 Indian patients demonstrated a substantial reduction of submental fat in 90% (45/50).³⁸ For each treatment, 5 mL of 30 mg/mL deoxycholic acid was injected. Serial sessions were conducted at 2-month intervals, and most (64% [32/50]) patients required 3 sessions to see a treatment effect. Adverse effects included transient swelling, lumpiness, and tenderness. A phase 2a investigation of the novel injectable small-molecule drug CBL-514 in 43 Asian and White participants found a significant improvement in the reduction in abdominal fat volume (P<.00001) and thickness (P<.0001) relative to baseline at higher doses (unit dose, 2.0 mg/cm² and 1.6 mg/cm²).³⁹ In addition to the adverse effects mentioned previously, pruritus, repeated urticaria, body rash, and fever also were reported.³⁹  

Radiofrequency Lipolysis—Radiofrequency is used for adipolysis through heat-induced apoptosis. To achieve this effect, adipose tissue must sustain a temperature of 42 °C to 45 °C for at least 15 minutes.⁴⁰ In one study, 4 treatments performed at 7-day intervals resulted in a statistically significant reduction in circumference to the treated areas of the inner and outer thighs without any reported adverse effects (P<0.001).⁴¹ Of note, there was 1 cm of distance between the applicator and the skin. The absence of direct contact with the skin is likely to reduce the risk for postprocedural complications in patients with SOC.

Magnetic Resonance Contouring—Magnetic resonance contouring with high-intensity focused electromagnetic technology is an emerging treatment modality for noninvasive body contouring. One distinguishing characteristic from other currently available noninvasive fat-­reduction therapies is that magnetic resonance may improve strength, tone, and muscle thickness.⁴² This modality is FDA approved for contouring of the buttocks and abdomen and employs electromagnetic energy to stimulate approximately 20,000 muscle contractions within a time frame of 30 minutes. Though the mechanisms causing benefits to muscular and adipose tissue have not been elucidated, current findings suggest that the contractions stimulate substantial lipolysis of adipocytes, resulting in the release of large amounts of free fatty acids that cause damage to nearby adipose tissue.⁴³ Multiple treatments are required over time to maintain effect. No major adverse effects have been reported. The likely mechanism of action of magnetic resonance contouring does not appear to pose an increased risk to patients with SOC.

Final Thoughts

One of the major roadblocks in distilling indications along with associated risks and benefits for nonsurgical cosmetic practices for patients with SOC is a void in the primary literature involving these populations. Clinical experience serves to address this deficit in combination with a thorough review of the literature. The 1064-nm Nd:YAG laser has shown clinical utility in the treatment of DPN, melanoma, and acne scars, but it poses financial constraints to the provider in comparison to modalities used for many years. Notably, NAF resurfacing is preferred for the management of acne scars in patients with SOC and continues to gain popularity for the treatment of photoaging. Regarding skin-tightening and body-contouring devices, studies performed in patients with SOC are limited and affected by factors such as small sample sizes, underrepresentation of FSTs IV through VI, short follow-up durations, and a lack of standardized outcome measures. Additionally, few studies assess pigmentary adverse effects or stratify results by skin type, which is critical given the higher risk for PIH in SOC. Ultrasound devices showed clinical utility in improvement of skin laxity, texture, and overall improvement. Patients with SOC respond well to skin-tightening devices due to the increased collagen synthesis. Regarding emerging devices for reduction of adipocytes, deoxycholic acid when injected showed notable improvement in fat reduction but also had adverse effects. As additional studies on cosmetic procedures in SOC emerge, an expansion of treatment options could be offered to this demographic group with confidence, provided proper treatment and follow-up protocols are in place.

Cosmetic laser procedures as well as energy-based fat reduction and body-contouring devices are increasingly popular among individuals with skin of color (SOC). Innovations in cosmetic devices and procedures tailored for SOC have allowed for the optimization of outcomes in this patient population. In this article, SOC is defined as darker skin types, including Fitzpatrick skin types (FSTs) IV to VI and ethnic backgrounds such as LatinX, African American, Southeast Asian, Native American, Pacific Islander, Middle Eastern, Asian, and African. Indications for laser treatment include dermatosis papulosa nigrans (DPN), acne scars, skin rejuvenation, and hyperpigmentation. There currently are 6 procedures for nonsurgical fat reduction that are approved by the US Food and Drug Administration (FDA): high-frequency focused ultrasound, cryolipolysis, laser lipolysis, injection lipolysis, radiofrequency lipolysis, and magnetic resonance contouring (Supplementary Table S1).¹

In this review, our initial focus is cosmetic laser ­procedures, encompassing FDA-cleared indications along with the associated risks and benefits in SOC populations. Subsequently, we delve into the realms of energy-based fat reduction and body contouring, offering a comprehensive overview of these noninvasive therapies and addressing considerations for efficacy and safety in these patients.

Dermatosis Papulosa Nigra

In patients with SOC, scissor excision, curettage, or electrodesiccation are the mainstay treatments for removal of DPN (Figure 1). Curettage and electrodesiccation can cause temporary postinflammatory hyperpigmentation (PIH) in these populations, while cryotherapy is not a preferred method in patients with SOC due to the possibility of cryotherapy-induced depigmentation. In a 14-patient split-face study comparing the 532-nm potassium titanyl phosphate (KTP) laser vs electrodesiccation in FSTs IV to VI, the KTP-treated side showed an improvement rate of 96%, while the electrodesiccation side showed an improvement rate of 79%. There was a statistically significant favorable experience for KTP with regard to pain tolerability (P=.002).² Complete resolution of lesions may be seen after 3 to 4 sessions at 4-week intervals. Additionally, the 1064-nm Nd:YAG laser was assessed for treatment of DPN in 2 patients, with 70% to 90% of lesions resolved after a single treatment with no complications.³

Most dermatologists still rely on curettage and electrodesiccation instead of laser therapy to remove DPNs in patients with SOC. The use of the Nd:YAG laser is promising yet expensive for the provider both to purchase and maintain. Electrodesiccation has been used by dermatology practices for decades and can be used without permanent discoloration. To minimize the risk for PIH, we recommend application of a healing ointment such as petroleum jelly or aloe vera gel to the treated lesions as well as lightening agents for PIH and daily use of sunscreen. Overall, providers do not need to purchase an expensive laser device for DPN removal.

Acne Scars

The invention of fractional technology in the early 2000s and its favorable safety profile have changed how dermatologists treat scarring in patients with SOC.^4,5 In fact, nonablative fractional (NAF) resurfacing is a preferred treatment modality for management of acne scars in patients with SOC.⁶ In one study of the 1550-nm erbium-doped fiber laser for treatment of acne scars (3 treatments at intervals of 2-3 weeks) in 10 Japanese patients, clinical improvement was seen in all patients and no severe adverse effects were reported.⁷ In another study, 27 Korean patients with FSTs IV and V were treated with an NAF resurfacing device for acne scars. Excellent results were reported in 30% (8/27) of patients, substantial improvement in 59% (16/27), and moderate improvement in 11% (3/27).⁸ To evaluate outcomes in patients treated with NAF resurfacing, a retrospective review of 961 treatments showed a hyperpigmentation rate of 11.6% in those with FST IV and 33% in FST V.⁹

In one study of the short-pulsed nonablative Nd:YAG laser, 9 patients with FSTs I to V and 2 patients with FSTs IV to V underwent 8 treatments at 2-week intervals. Three blinded observers found a 29% improvement in the Global Acne Scar Severity score, while 89% (8/9) of patients self-reported subjective improvement in their acne scars.¹⁰

The 755-nm picosecond laser and diffractive lens array also have been shown to reduce the appearance of acne scars in patients with SOC, as shown via serial photography in a retrospective study of 56 patients with FSTs IV to VI. Transient hyperpigmentation, erythema, and edema were reported.¹¹

Nonablative laser therapy is preferred for skin rejuvenation in patients with SOC due to a reduced risk for postprocedural hyperpigmentation.¹¹ Ablative resurfacing (eg, CO₂ laser) poses major risks for postprocedural hyperpigmentation, hypopigmentation, and scar formation and therefore should be avoided in these populations.^12,13 A study involving 30 Asian patients (FSTs III-IV) demonstrated that the 1550-nm fractional laser was well tolerated, though higher treatment densities and fluences may lead to temporary adverse effects such as increased redness, swelling, and pain (P<.01).¹⁴ Furthermore, greater density was shown to cause higher levels of redness, hyperpigmentation, and swelling in comparison to higher fluence settings. Of note, patient satisfaction was markedly higher in patients who underwent treatment with higher fluence settings but not in patients with higher densities (P<.05). Postprocedural hyperpigmentation was noted in 6.7% (2/30) of patients studied.¹⁴ In another study, 8 patients with FSTs II to V were treated with either the 1064-nm long-pulsed Nd:YAG laser or the grid fractional monopolar radiofrequency laser.¹⁵ All participants experienced a significant decrease in mean wrinkle count using the Lemperle wrinkle assessment (P<.05). A significant decrease in mean wrinkle assessment score from 3.5 to 3.17 in clinical assessment and a decrease from 3.165 to 2.33 for photographic assessment was noted in patients treated with the grid laser (P<.05). A similar decrease in mean wrinkle assessment score was observed in the Nd:YAG group, with a mean decrease of 3.665 to 2.83 after 2 months for clinical assessment and 3.5 to 2.67 for photographic assessment. Among all patients in the study, 68% (6/8) experienced erythema, 25% (2/8) had a burning sensation, and 25% (2/8) experienced urticaria immediately postprocedure.¹⁵

Nonablative fractional resurfacing is preferred for the management of acne scars in patients with SOC. Adverse effects such as hyperpigmentation typically are transient, and the risk may be minimized with strict photoprotective practices following the procedure. Furthermore, avoidance of topicals containing exfoliants or α-hydroxy acids applied to the treated area following the procedure also may mitigate the risk for postprocedural hyperpigmentation.¹⁶ If hyperpigmentation does occur, use of topical melanogenesis inhibitors such as hydroquinone, kojic acid, or azelaic acid has shown some utility in practice.

Skin Rejuvenation

Nonablative fractional lasers (NAFLs) continue to be popular for treatment of photoaging. One study including 10 Asian patients (FSTs III-V) assessed the 1440-nm diode-based fractional laser for facial rejuvenation.¹⁷ After 4 sessions at 2-week intervals, 80% (8/10) of patients reported decreased skin roughness after both the second and third treatments, while 90% (9/10) had improved texture 1 month after the final procedure. Adverse effects included moderate facial edema and one case of transient hyperpigmentation.¹⁷ Another study reported a significant reduction in pore score (P<.002), with patients noting an overall improvement in skin appearance with minimal erythema, dryness, and flaking following 6 sessions at 2-week intervals using the 1440-nm diode-based fractional laser.¹⁸

The 1550-nm diode fractional laser significantly improved skin pigmentation (P<.001) and texture (P<.001) in 10 patients with FSTs II to IV following 5 sessions at 2- to 3-week intervals, with self-resolving erythema and edema posttreatment (Supplementary Table S2).¹⁹ Overall, NAFLs for the treatment of photoaging are effective with minimal adverse effects (eg, facial edema), which can be reduced with application of cold compression to the face and elevation of the head following treatment as well as the use of additional pillows during overnight sleep.

Laser Treatment for Hyperpigmentation Disorders

Melasma—The FDA recently approved fractional photothermolysis for the treatment of melasma; however, due to the risk for hyperpigmentation given its pathogenesis linked to hyperactive melanocytes, this laser is not considered a first-line therapy for melasma.²⁰ In a split-face, randomized study, 22 patients with FSTs III to V who were diagnosed with either dermal or mixed-type melasma were treated with a low-fluence Q-switched Nd:YAG laser combined with hydroquinone 2% vs hydroquinone 2% alone (Supplementary Table S3).²¹ Each patient was treated weekly for 5 consecutive weeks. The laser-treated side was found to reach an average of 92.5% improvement compared with 19.7% on the hydroquinone-only side. Three of the 22 (13.6%) patients developed mottled hypopigmentation after 5 laser treatments, and 8 (36.4%) developed confetti-type hypopigmentation. Four (18.2%) patients developed rebound hyperpigmentation, and all 22 patients experienced recurrence of melasma by 12 weeks posttreatment.²¹

First-line treatment for melasma involves the application of topical lightening agents such as hydroquinone, azelaic acid, kojic acid, retinoids, or mild topical steroids. Combining laser technology with topical medications can enhance treatment outcomes, particularly yielding positive results for patients with persistent pigmentation concerns. Notably, utilization of 650-microsecond technology with the 1064-nm Nd:YAG laser is considered superior in clinical practice, especially for patients with FSTs IV through VI.

Postinflammatory Hyperpigmentation—A retrospective evaluation of 61 patients with FSTs IV to VI with PIH treated with a 1927-nm NAFL showed a mean improvement of 43.24%, as assessed by 2 dermatologists.²² Additionally, the Nd:YAG 1064-nm 650-microsecond pulse duration laser is an emerging treatment that delivers high and low fluences between 4 J/cm² and 255 J/cm² within a single 650-microsecond pulse duration.²³ The short-pulse duration avoids overheating the skin, mitigating procedural discomfort and the risk for adverse effects commonly seen with the previous generation of low-pulsed lasers. In addition to PIH, this laser has been successfully used to treat pseudofolliculitis barbae.²⁴

Solar Lentigos—In a split-face study treating solar lentigos in Asian patients, 4 treatments with a low-pulsed KTP 532-nm laser were administered with and without a second treatment with a low-pulsed 1064-nm Nd:YAG laser.²⁵ Scoring of a modified pigment severity index and measurement of the melanin index showed that skin treated with the low-pulsed 532-nm laser alone and in combination with the low-pulsed 1064-nm Nd:YAG laser resulted in improvement at 3 months’ follow-up. However, there was no difference between the 2 sides of the face, leading the researchers to conclude that the low-pulsed 532-nm laser appears to be safe and effective for treatment of solar lentigos in Asian patients and does not require the addition of the low-pulsed 1064-nm laser.²⁵  

To avoid hyperpigmentation in patients with SOC, strict photoprotection to the treated areas should be advised. Proper cooling of the laser-treated area is required to minimize PIH, as cooling decreases tissue damage and excessive thermal injury. Test spots should be considered prior to initiation of the full laser treatment. Hydroquinone in a 4% concentration applied daily for 2 weeks preprocedure commonly is employed to reduce the risk for postprocedural hyperpigmentation in clinical practice.^26,27

Skin Tightening and Body Contouring

In general, skin-tightening and body-contouring devices are among the most sought-after procedures. Studies performed in patients with SOC are limited. Herein, we provide background on why these devices are favorable for patients with SOC and our experiences in using them. A summary of these devices can be found in Supplementary Table S4.

Radiofrequency Skin Tightening—Radiofrequency devices are utilized for skin tightening as well as mild fat reduction; they commonly are used on the abdomen, thighs, buttocks, and face.²⁸ People with SOC are more responsive to radiofrequency skin-tightening therapy due to higher baseline collagen content and dermal thickness, more sebaceous activity and skin elasticity, and more melanin content which offers protective thermal buffering.^29,30 As the radiofrequency device emits heat, penetrating deep into the dermis, it generates collagen remodeling and synthesis within 4 to 6 months posttreatment.

Nonsurgical Fat Reduction

Procedures for nonsurgical fat reduction are favorable due to minimal recovery time, manageable cost, and an in-office procedure setting. As noted previously, there are 6 FDA-indicated interventions for nonsurgical fat reduction: ultrasonography, cryolipolysis, laser lipolysis, injection lipolysis, radiofrequency lipolysis, and magnetic resonance contouring.³¹

Ultrasonography—Ultrasound devices designed for body contouring are used for skin tightening and mild fat reduction through the use of acoustic energy.³² These devices can be divided into 2 categories: high frequency and low frequency, with the high-frequency devices being the most popular. High-frequency ultrasound energy produces heat at target sites, which induces necrosis of adipocytes and stimulates collagen remodeling within the tissue matrix.³³ Tissue temperatures above 56°C stimulate adipocyte necrosis while sparing nearby nerves and vessels.²⁸ Because of the short duration of the procedure, the risk for epidermal damage is minimal. Contrary to high-frequency ultrasonography, focus-pulsed ultrasonography employs low-frequency waves to induce the mechanical disruption of adipocytes, which is generally better tolerated due to its nonthermal mechanism. The latter may be advantageous in patients with SOC due to a reduced risk for thermal injury to the epidermis. Multiple treatments often are needed at 3- to 4-week intervals, resulting in gradual improvement observed over 2 to 6 months. One study of microfocused ultrasonography in 25 Asian patients for treatment of face and neck laxity reported that skin laxity was improved or much improved in 84% (21/25) of patients following treatment.³⁴ Adverse effects were reported as mild and transient, resolving within 90 days.³⁴ Ultrasound devices also were shown to improve wrinkles, texture, and overall appearance of the skin in a 71-year-old African American woman 4 months following treatment (Figure 2). These photographs highlight the clinical utility of a microfocused ultrasound skin-tightening treatment in African American patients.

Cryolipolysis—Cryolipolysis is a noninvasive body contouring procedure that employs controlled cooling to induce subcutaneous panniculitis. Through cold-induced apoptosis of adipocytes, this procedure selectively reduces adipose tissue in localized areas such as the flank, abdomen, thighs, buttocks, back, submental area, and upper arms. The temperature used in cryolipolysis is approximately –10°C.³⁵ The lethal temperature for melanocytes is –4 °C, below which melanocyte apoptosis may be induced, resulting in depigmentation. Given the prolonged contact of the skin with a cryolipolysis device for up to 60 minutes during a body-contouring procedure, there is a risk for resultant depigmentation in darker skin types. Controlled studies are needed to fully evaluate the safety and efficacy of cryolipolysis in patients with SOC. One retrospective study of cryolipolysis applied to the abdomen and upper arm of 4122 Asian patients reported a significant (P<.05) reduction in the circumference of the abdomen and the upper-arm areas. No long-term adverse effects were reported.³⁶

Laser Lipolysis—The 1060-nm diode laser for body contouring selectively destroys adipose tissue, resulting in body contouring via thermally induced inflammation. Hyperthermic exposure for 15 minutes selectively elevates adipocyte temperature between 42°C to 47°C, which triggers apoptosis and the eventual clearance of destroyed cells from the interstitial space.³⁷ The selectivity of the 1060-nm wavelength coupled with the device’s contact cooling system preserves the overlying skin and adnexa during the procedure,³⁷ which would minimize epidermal damage that may induce dyspigmentation in patients with SOC. No notable adverse effects or dyspigmentation have been reported using this device.

Injection Lipolysis—Deoxycholic acid is an injectable adipocytolytic for the reduction of submental fat. It nonselectively lyses muscle and other adjacent nonfatty tissue. One study of 50 Indian patients demonstrated a substantial reduction of submental fat in 90% (45/50).³⁸ For each treatment, 5 mL of 30 mg/mL deoxycholic acid was injected. Serial sessions were conducted at 2-month intervals, and most (64% [32/50]) patients required 3 sessions to see a treatment effect. Adverse effects included transient swelling, lumpiness, and tenderness. A phase 2a investigation of the novel injectable small-molecule drug CBL-514 in 43 Asian and White participants found a significant improvement in the reduction in abdominal fat volume (P<.00001) and thickness (P<.0001) relative to baseline at higher doses (unit dose, 2.0 mg/cm² and 1.6 mg/cm²).³⁹ In addition to the adverse effects mentioned previously, pruritus, repeated urticaria, body rash, and fever also were reported.³⁹  

Radiofrequency Lipolysis—Radiofrequency is used for adipolysis through heat-induced apoptosis. To achieve this effect, adipose tissue must sustain a temperature of 42 °C to 45 °C for at least 15 minutes.⁴⁰ In one study, 4 treatments performed at 7-day intervals resulted in a statistically significant reduction in circumference to the treated areas of the inner and outer thighs without any reported adverse effects (P<0.001).⁴¹ Of note, there was 1 cm of distance between the applicator and the skin. The absence of direct contact with the skin is likely to reduce the risk for postprocedural complications in patients with SOC.

Magnetic Resonance Contouring—Magnetic resonance contouring with high-intensity focused electromagnetic technology is an emerging treatment modality for noninvasive body contouring. One distinguishing characteristic from other currently available noninvasive fat-­reduction therapies is that magnetic resonance may improve strength, tone, and muscle thickness.⁴² This modality is FDA approved for contouring of the buttocks and abdomen and employs electromagnetic energy to stimulate approximately 20,000 muscle contractions within a time frame of 30 minutes. Though the mechanisms causing benefits to muscular and adipose tissue have not been elucidated, current findings suggest that the contractions stimulate substantial lipolysis of adipocytes, resulting in the release of large amounts of free fatty acids that cause damage to nearby adipose tissue.⁴³ Multiple treatments are required over time to maintain effect. No major adverse effects have been reported. The likely mechanism of action of magnetic resonance contouring does not appear to pose an increased risk to patients with SOC.

Final Thoughts

One of the major roadblocks in distilling indications along with associated risks and benefits for nonsurgical cosmetic practices for patients with SOC is a void in the primary literature involving these populations. Clinical experience serves to address this deficit in combination with a thorough review of the literature. The 1064-nm Nd:YAG laser has shown clinical utility in the treatment of DPN, melanoma, and acne scars, but it poses financial constraints to the provider in comparison to modalities used for many years. Notably, NAF resurfacing is preferred for the management of acne scars in patients with SOC and continues to gain popularity for the treatment of photoaging. Regarding skin-tightening and body-contouring devices, studies performed in patients with SOC are limited and affected by factors such as small sample sizes, underrepresentation of FSTs IV through VI, short follow-up durations, and a lack of standardized outcome measures. Additionally, few studies assess pigmentary adverse effects or stratify results by skin type, which is critical given the higher risk for PIH in SOC. Ultrasound devices showed clinical utility in improvement of skin laxity, texture, and overall improvement. Patients with SOC respond well to skin-tightening devices due to the increased collagen synthesis. Regarding emerging devices for reduction of adipocytes, deoxycholic acid when injected showed notable improvement in fat reduction but also had adverse effects. As additional studies on cosmetic procedures in SOC emerge, an expansion of treatment options could be offered to this demographic group with confidence, provided proper treatment and follow-up protocols are in place.

Cosmetic laser procedures as well as energy-based fat reduction and body-contouring devices are increasingly popular among individuals with skin of color (SOC). Innovations in cosmetic devices and procedures tailored for SOC have allowed for the optimization of outcomes in this patient population. In this article, SOC is defined as darker skin types, including Fitzpatrick skin types (FSTs) IV to VI and ethnic backgrounds such as LatinX, African American, Southeast Asian, Native American, Pacific Islander, Middle Eastern, Asian, and African. Indications for laser treatment include dermatosis papulosa nigrans (DPN), acne scars, skin rejuvenation, and hyperpigmentation. There currently are 6 procedures for nonsurgical fat reduction that are approved by the US Food and Drug Administration (FDA): high-frequency focused ultrasound, cryolipolysis, laser lipolysis, injection lipolysis, radiofrequency lipolysis, and magnetic resonance contouring (Supplementary Table S1).¹

In this review, our initial focus is cosmetic laser ­procedures, encompassing FDA-cleared indications along with the associated risks and benefits in SOC populations. Subsequently, we delve into the realms of energy-based fat reduction and body contouring, offering a comprehensive overview of these noninvasive therapies and addressing considerations for efficacy and safety in these patients.

Dermatosis Papulosa Nigra

In patients with SOC, scissor excision, curettage, or electrodesiccation are the mainstay treatments for removal of DPN (Figure 1). Curettage and electrodesiccation can cause temporary postinflammatory hyperpigmentation (PIH) in these populations, while cryotherapy is not a preferred method in patients with SOC due to the possibility of cryotherapy-induced depigmentation. In a 14-patient split-face study comparing the 532-nm potassium titanyl phosphate (KTP) laser vs electrodesiccation in FSTs IV to VI, the KTP-treated side showed an improvement rate of 96%, while the electrodesiccation side showed an improvement rate of 79%. There was a statistically significant favorable experience for KTP with regard to pain tolerability (P=.002).² Complete resolution of lesions may be seen after 3 to 4 sessions at 4-week intervals. Additionally, the 1064-nm Nd:YAG laser was assessed for treatment of DPN in 2 patients, with 70% to 90% of lesions resolved after a single treatment with no complications.³

Most dermatologists still rely on curettage and electrodesiccation instead of laser therapy to remove DPNs in patients with SOC. The use of the Nd:YAG laser is promising yet expensive for the provider both to purchase and maintain. Electrodesiccation has been used by dermatology practices for decades and can be used without permanent discoloration. To minimize the risk for PIH, we recommend application of a healing ointment such as petroleum jelly or aloe vera gel to the treated lesions as well as lightening agents for PIH and daily use of sunscreen. Overall, providers do not need to purchase an expensive laser device for DPN removal.

Acne Scars

The invention of fractional technology in the early 2000s and its favorable safety profile have changed how dermatologists treat scarring in patients with SOC.^4,5 In fact, nonablative fractional (NAF) resurfacing is a preferred treatment modality for management of acne scars in patients with SOC.⁶ In one study of the 1550-nm erbium-doped fiber laser for treatment of acne scars (3 treatments at intervals of 2-3 weeks) in 10 Japanese patients, clinical improvement was seen in all patients and no severe adverse effects were reported.⁷ In another study, 27 Korean patients with FSTs IV and V were treated with an NAF resurfacing device for acne scars. Excellent results were reported in 30% (8/27) of patients, substantial improvement in 59% (16/27), and moderate improvement in 11% (3/27).⁸ To evaluate outcomes in patients treated with NAF resurfacing, a retrospective review of 961 treatments showed a hyperpigmentation rate of 11.6% in those with FST IV and 33% in FST V.⁹

In one study of the short-pulsed nonablative Nd:YAG laser, 9 patients with FSTs I to V and 2 patients with FSTs IV to V underwent 8 treatments at 2-week intervals. Three blinded observers found a 29% improvement in the Global Acne Scar Severity score, while 89% (8/9) of patients self-reported subjective improvement in their acne scars.¹⁰

The 755-nm picosecond laser and diffractive lens array also have been shown to reduce the appearance of acne scars in patients with SOC, as shown via serial photography in a retrospective study of 56 patients with FSTs IV to VI. Transient hyperpigmentation, erythema, and edema were reported.¹¹

Nonablative laser therapy is preferred for skin rejuvenation in patients with SOC due to a reduced risk for postprocedural hyperpigmentation.¹¹ Ablative resurfacing (eg, CO₂ laser) poses major risks for postprocedural hyperpigmentation, hypopigmentation, and scar formation and therefore should be avoided in these populations.^12,13 A study involving 30 Asian patients (FSTs III-IV) demonstrated that the 1550-nm fractional laser was well tolerated, though higher treatment densities and fluences may lead to temporary adverse effects such as increased redness, swelling, and pain (P<.01).¹⁴ Furthermore, greater density was shown to cause higher levels of redness, hyperpigmentation, and swelling in comparison to higher fluence settings. Of note, patient satisfaction was markedly higher in patients who underwent treatment with higher fluence settings but not in patients with higher densities (P<.05). Postprocedural hyperpigmentation was noted in 6.7% (2/30) of patients studied.¹⁴ In another study, 8 patients with FSTs II to V were treated with either the 1064-nm long-pulsed Nd:YAG laser or the grid fractional monopolar radiofrequency laser.¹⁵ All participants experienced a significant decrease in mean wrinkle count using the Lemperle wrinkle assessment (P<.05). A significant decrease in mean wrinkle assessment score from 3.5 to 3.17 in clinical assessment and a decrease from 3.165 to 2.33 for photographic assessment was noted in patients treated with the grid laser (P<.05). A similar decrease in mean wrinkle assessment score was observed in the Nd:YAG group, with a mean decrease of 3.665 to 2.83 after 2 months for clinical assessment and 3.5 to 2.67 for photographic assessment. Among all patients in the study, 68% (6/8) experienced erythema, 25% (2/8) had a burning sensation, and 25% (2/8) experienced urticaria immediately postprocedure.¹⁵

Nonablative fractional resurfacing is preferred for the management of acne scars in patients with SOC. Adverse effects such as hyperpigmentation typically are transient, and the risk may be minimized with strict photoprotective practices following the procedure. Furthermore, avoidance of topicals containing exfoliants or α-hydroxy acids applied to the treated area following the procedure also may mitigate the risk for postprocedural hyperpigmentation.¹⁶ If hyperpigmentation does occur, use of topical melanogenesis inhibitors such as hydroquinone, kojic acid, or azelaic acid has shown some utility in practice.

Skin Rejuvenation

Nonablative fractional lasers (NAFLs) continue to be popular for treatment of photoaging. One study including 10 Asian patients (FSTs III-V) assessed the 1440-nm diode-based fractional laser for facial rejuvenation.¹⁷ After 4 sessions at 2-week intervals, 80% (8/10) of patients reported decreased skin roughness after both the second and third treatments, while 90% (9/10) had improved texture 1 month after the final procedure. Adverse effects included moderate facial edema and one case of transient hyperpigmentation.¹⁷ Another study reported a significant reduction in pore score (P<.002), with patients noting an overall improvement in skin appearance with minimal erythema, dryness, and flaking following 6 sessions at 2-week intervals using the 1440-nm diode-based fractional laser.¹⁸

The 1550-nm diode fractional laser significantly improved skin pigmentation (P<.001) and texture (P<.001) in 10 patients with FSTs II to IV following 5 sessions at 2- to 3-week intervals, with self-resolving erythema and edema posttreatment (Supplementary Table S2).¹⁹ Overall, NAFLs for the treatment of photoaging are effective with minimal adverse effects (eg, facial edema), which can be reduced with application of cold compression to the face and elevation of the head following treatment as well as the use of additional pillows during overnight sleep.

Laser Treatment for Hyperpigmentation Disorders

Melasma—The FDA recently approved fractional photothermolysis for the treatment of melasma; however, due to the risk for hyperpigmentation given its pathogenesis linked to hyperactive melanocytes, this laser is not considered a first-line therapy for melasma.²⁰ In a split-face, randomized study, 22 patients with FSTs III to V who were diagnosed with either dermal or mixed-type melasma were treated with a low-fluence Q-switched Nd:YAG laser combined with hydroquinone 2% vs hydroquinone 2% alone (Supplementary Table S3).²¹ Each patient was treated weekly for 5 consecutive weeks. The laser-treated side was found to reach an average of 92.5% improvement compared with 19.7% on the hydroquinone-only side. Three of the 22 (13.6%) patients developed mottled hypopigmentation after 5 laser treatments, and 8 (36.4%) developed confetti-type hypopigmentation. Four (18.2%) patients developed rebound hyperpigmentation, and all 22 patients experienced recurrence of melasma by 12 weeks posttreatment.²¹

First-line treatment for melasma involves the application of topical lightening agents such as hydroquinone, azelaic acid, kojic acid, retinoids, or mild topical steroids. Combining laser technology with topical medications can enhance treatment outcomes, particularly yielding positive results for patients with persistent pigmentation concerns. Notably, utilization of 650-microsecond technology with the 1064-nm Nd:YAG laser is considered superior in clinical practice, especially for patients with FSTs IV through VI.

Postinflammatory Hyperpigmentation—A retrospective evaluation of 61 patients with FSTs IV to VI with PIH treated with a 1927-nm NAFL showed a mean improvement of 43.24%, as assessed by 2 dermatologists.²² Additionally, the Nd:YAG 1064-nm 650-microsecond pulse duration laser is an emerging treatment that delivers high and low fluences between 4 J/cm² and 255 J/cm² within a single 650-microsecond pulse duration.²³ The short-pulse duration avoids overheating the skin, mitigating procedural discomfort and the risk for adverse effects commonly seen with the previous generation of low-pulsed lasers. In addition to PIH, this laser has been successfully used to treat pseudofolliculitis barbae.²⁴

Solar Lentigos—In a split-face study treating solar lentigos in Asian patients, 4 treatments with a low-pulsed KTP 532-nm laser were administered with and without a second treatment with a low-pulsed 1064-nm Nd:YAG laser.²⁵ Scoring of a modified pigment severity index and measurement of the melanin index showed that skin treated with the low-pulsed 532-nm laser alone and in combination with the low-pulsed 1064-nm Nd:YAG laser resulted in improvement at 3 months’ follow-up. However, there was no difference between the 2 sides of the face, leading the researchers to conclude that the low-pulsed 532-nm laser appears to be safe and effective for treatment of solar lentigos in Asian patients and does not require the addition of the low-pulsed 1064-nm laser.²⁵  

To avoid hyperpigmentation in patients with SOC, strict photoprotection to the treated areas should be advised. Proper cooling of the laser-treated area is required to minimize PIH, as cooling decreases tissue damage and excessive thermal injury. Test spots should be considered prior to initiation of the full laser treatment. Hydroquinone in a 4% concentration applied daily for 2 weeks preprocedure commonly is employed to reduce the risk for postprocedural hyperpigmentation in clinical practice.^26,27

Skin Tightening and Body Contouring

In general, skin-tightening and body-contouring devices are among the most sought-after procedures. Studies performed in patients with SOC are limited. Herein, we provide background on why these devices are favorable for patients with SOC and our experiences in using them. A summary of these devices can be found in Supplementary Table S4.

Radiofrequency Skin Tightening—Radiofrequency devices are utilized for skin tightening as well as mild fat reduction; they commonly are used on the abdomen, thighs, buttocks, and face.²⁸ People with SOC are more responsive to radiofrequency skin-tightening therapy due to higher baseline collagen content and dermal thickness, more sebaceous activity and skin elasticity, and more melanin content which offers protective thermal buffering.^29,30 As the radiofrequency device emits heat, penetrating deep into the dermis, it generates collagen remodeling and synthesis within 4 to 6 months posttreatment.

Nonsurgical Fat Reduction

Procedures for nonsurgical fat reduction are favorable due to minimal recovery time, manageable cost, and an in-office procedure setting. As noted previously, there are 6 FDA-indicated interventions for nonsurgical fat reduction: ultrasonography, cryolipolysis, laser lipolysis, injection lipolysis, radiofrequency lipolysis, and magnetic resonance contouring.³¹

Ultrasonography—Ultrasound devices designed for body contouring are used for skin tightening and mild fat reduction through the use of acoustic energy.³² These devices can be divided into 2 categories: high frequency and low frequency, with the high-frequency devices being the most popular. High-frequency ultrasound energy produces heat at target sites, which induces necrosis of adipocytes and stimulates collagen remodeling within the tissue matrix.³³ Tissue temperatures above 56°C stimulate adipocyte necrosis while sparing nearby nerves and vessels.²⁸ Because of the short duration of the procedure, the risk for epidermal damage is minimal. Contrary to high-frequency ultrasonography, focus-pulsed ultrasonography employs low-frequency waves to induce the mechanical disruption of adipocytes, which is generally better tolerated due to its nonthermal mechanism. The latter may be advantageous in patients with SOC due to a reduced risk for thermal injury to the epidermis. Multiple treatments often are needed at 3- to 4-week intervals, resulting in gradual improvement observed over 2 to 6 months. One study of microfocused ultrasonography in 25 Asian patients for treatment of face and neck laxity reported that skin laxity was improved or much improved in 84% (21/25) of patients following treatment.³⁴ Adverse effects were reported as mild and transient, resolving within 90 days.³⁴ Ultrasound devices also were shown to improve wrinkles, texture, and overall appearance of the skin in a 71-year-old African American woman 4 months following treatment (Figure 2). These photographs highlight the clinical utility of a microfocused ultrasound skin-tightening treatment in African American patients.

Cryolipolysis—Cryolipolysis is a noninvasive body contouring procedure that employs controlled cooling to induce subcutaneous panniculitis. Through cold-induced apoptosis of adipocytes, this procedure selectively reduces adipose tissue in localized areas such as the flank, abdomen, thighs, buttocks, back, submental area, and upper arms. The temperature used in cryolipolysis is approximately –10°C.³⁵ The lethal temperature for melanocytes is –4 °C, below which melanocyte apoptosis may be induced, resulting in depigmentation. Given the prolonged contact of the skin with a cryolipolysis device for up to 60 minutes during a body-contouring procedure, there is a risk for resultant depigmentation in darker skin types. Controlled studies are needed to fully evaluate the safety and efficacy of cryolipolysis in patients with SOC. One retrospective study of cryolipolysis applied to the abdomen and upper arm of 4122 Asian patients reported a significant (P<.05) reduction in the circumference of the abdomen and the upper-arm areas. No long-term adverse effects were reported.³⁶

Laser Lipolysis—The 1060-nm diode laser for body contouring selectively destroys adipose tissue, resulting in body contouring via thermally induced inflammation. Hyperthermic exposure for 15 minutes selectively elevates adipocyte temperature between 42°C to 47°C, which triggers apoptosis and the eventual clearance of destroyed cells from the interstitial space.³⁷ The selectivity of the 1060-nm wavelength coupled with the device’s contact cooling system preserves the overlying skin and adnexa during the procedure,³⁷ which would minimize epidermal damage that may induce dyspigmentation in patients with SOC. No notable adverse effects or dyspigmentation have been reported using this device.

Injection Lipolysis—Deoxycholic acid is an injectable adipocytolytic for the reduction of submental fat. It nonselectively lyses muscle and other adjacent nonfatty tissue. One study of 50 Indian patients demonstrated a substantial reduction of submental fat in 90% (45/50).³⁸ For each treatment, 5 mL of 30 mg/mL deoxycholic acid was injected. Serial sessions were conducted at 2-month intervals, and most (64% [32/50]) patients required 3 sessions to see a treatment effect. Adverse effects included transient swelling, lumpiness, and tenderness. A phase 2a investigation of the novel injectable small-molecule drug CBL-514 in 43 Asian and White participants found a significant improvement in the reduction in abdominal fat volume (P<.00001) and thickness (P<.0001) relative to baseline at higher doses (unit dose, 2.0 mg/cm² and 1.6 mg/cm²).³⁹ In addition to the adverse effects mentioned previously, pruritus, repeated urticaria, body rash, and fever also were reported.³⁹  

Radiofrequency Lipolysis—Radiofrequency is used for adipolysis through heat-induced apoptosis. To achieve this effect, adipose tissue must sustain a temperature of 42 °C to 45 °C for at least 15 minutes.⁴⁰ In one study, 4 treatments performed at 7-day intervals resulted in a statistically significant reduction in circumference to the treated areas of the inner and outer thighs without any reported adverse effects (P<0.001).⁴¹ Of note, there was 1 cm of distance between the applicator and the skin. The absence of direct contact with the skin is likely to reduce the risk for postprocedural complications in patients with SOC.

Magnetic Resonance Contouring—Magnetic resonance contouring with high-intensity focused electromagnetic technology is an emerging treatment modality for noninvasive body contouring. One distinguishing characteristic from other currently available noninvasive fat-­reduction therapies is that magnetic resonance may improve strength, tone, and muscle thickness.⁴² This modality is FDA approved for contouring of the buttocks and abdomen and employs electromagnetic energy to stimulate approximately 20,000 muscle contractions within a time frame of 30 minutes. Though the mechanisms causing benefits to muscular and adipose tissue have not been elucidated, current findings suggest that the contractions stimulate substantial lipolysis of adipocytes, resulting in the release of large amounts of free fatty acids that cause damage to nearby adipose tissue.⁴³ Multiple treatments are required over time to maintain effect. No major adverse effects have been reported. The likely mechanism of action of magnetic resonance contouring does not appear to pose an increased risk to patients with SOC.

Final Thoughts

One of the major roadblocks in distilling indications along with associated risks and benefits for nonsurgical cosmetic practices for patients with SOC is a void in the primary literature involving these populations. Clinical experience serves to address this deficit in combination with a thorough review of the literature. The 1064-nm Nd:YAG laser has shown clinical utility in the treatment of DPN, melanoma, and acne scars, but it poses financial constraints to the provider in comparison to modalities used for many years. Notably, NAF resurfacing is preferred for the management of acne scars in patients with SOC and continues to gain popularity for the treatment of photoaging. Regarding skin-tightening and body-contouring devices, studies performed in patients with SOC are limited and affected by factors such as small sample sizes, underrepresentation of FSTs IV through VI, short follow-up durations, and a lack of standardized outcome measures. Additionally, few studies assess pigmentary adverse effects or stratify results by skin type, which is critical given the higher risk for PIH in SOC. Ultrasound devices showed clinical utility in improvement of skin laxity, texture, and overall improvement. Patients with SOC respond well to skin-tightening devices due to the increased collagen synthesis. Regarding emerging devices for reduction of adipocytes, deoxycholic acid when injected showed notable improvement in fat reduction but also had adverse effects. As additional studies on cosmetic procedures in SOC emerge, an expansion of treatment options could be offered to this demographic group with confidence, provided proper treatment and follow-up protocols are in place.

Personal electronic devices have become more common as consumer-driven health and entertainment practices continue to increase in popularity. A wide variety of devices including smartphones, headphones and earbuds, fitness watches, and continuous glucose monitors (CGMs) allow consumers to collect data and personalize their daily activities and health practices. The global market for fitness tracking devices alone was valued at $62.03 billion in 2024 and is projected to grow to $290.85 billion by 2032.¹ Accordingly, the growing demand for continuous data tracking has led to new and prolonged skin contact with these devices, which have become emerging sources of allergic contact dermatitis (ACD). In this article, we provide a summary of the potential allergenicity of personal electronic devices with a focus on wearable devices, including clinical manifestations, reported allergens, and patch testing and management considerations (Table^2-28).

Earbuds and Headphones

Wireless earbuds and headphones are used for listening to media and may contain microphones for voice calls. Earbuds are inserted into the ears while headphones are worn over the ears with a connecting band across the scalp. These devices frequently are worn during physical activity and thus in the setting of moist sweaty environments and mechanical friction on the skin. Depending on the style of the earbuds or headphones, associated ACD may manifest as acute or chronic pruritic eczema involving the inner and/or outer ears and potentially the periauricular areas or scalp.² In a reported case of earbud ACD, the patient first presented to an otolaryngologist before being referred to a dermatologist for further evaluation and patch testing.⁹ Clinicians may be unfamiliar with these devices as a source of ACD or may potentially overlook inner ear canal manifestations, which may delay diagnosis.

Allergens reported in earbuds include (meth)acrylates,^4-6 nickel, gold,⁸ and silicone.⁹ Apple AirPods and Samsung Galaxy Buds disclose the presence of acrylates and nickel.^5,6 Cases also have been reported of ACD to gold earbud microphones⁸ and unknown allergens within silicone tips.^4,9 Acrylates, named the 2012 Allergen of the Year by the American Contact Dermatitis Society,²⁹ are used in a wide variety of consumer products as adhesives and coatings and are among the most frequently suspected headphone allergens.⁴ While fully polymerized acrylates theoretically are nonallergenic, residual acrylic monomers are potent allergens that may be found in in these products due to incomplete curing or polymer breakdown.²⁹ It remains unclear whether earbud allergen concentrations are sufficient to induce sensitization or merely elicit ACD in previously sensitized users.²⁹ Among patients with earbud ACD, the finding of inconsistent patch test reactions/cross-reactions led to the hypothesis that these headphones may contain an unidentified proprietary (meth)acrylate.⁴

Headphones, often utilized by runners and gymgoers for their comfort and fit, also have gained recent attention for their unique allergen profiles. In 2024, a case series described primary sensitization to octylisothiazolinone causing severe headphone-related ACD.³ This preservative, which is in the same family as methylchloroisothiazolinone/methylisothiazolinone, is used as a biocide in the leather or faux leather that encases the foam padding of headphones.³ Another case report highlighted ACD caused by methylisothiazolinone, methylchloroisothiazolinone, and octylisothiazolinone present in various components of a pair of headphones.² These cases are notable, as European legislation limiting the use of methylchloroisothiazolinone/methylisothiazolinone in personal care products does not apply to inclusion of isothiazolinones in other product categories, such as detergents, paints, glues, and personal electronic devices.

Mobile Phones

Mobile phones are a staple in modern society, used for a multitude of tasks including communication, internet browsing, entertainment, and activity tracking. In the early 2000s, mobile phone ACD primarily manifested on the lateral face, ears, and periauricular regions,¹² as well as the thighs from carriage in pants pockets. Early cases of mobile phone ACD were attributed to metals including chromium¹⁶ and nickel.¹⁴ At that time, lengthy and frequent phone calls with the device against the ear were thought to increase exposure to metal allergens.³⁰ More recently, as the utility of these devices has evolved, ACD has been reported to manifest on the fingers and hands associated with contact with cell phone cases, accessories, and screen protectors (Figure). In one report, a 17-year-old boy with chronic eczema of the palms was diagnosed with ACD to the rubber-related chemicals paraphenylenediamine and N-cyclohexyl-N-phenyl-4-phenylenediamine, confirmed via chemical analysis to be present in a phone case the patient used during daily gaming.¹⁷ Similarly, another case of palmar ACD resulted from thiuram rubber accelerators in a phone case.¹⁸ Most recently, a Japanese patient with a history of skin reactions to costume jewelry developed ACD involving the proximal middle finger due to exposure to nickel in a ring-grip phone case.¹¹ While the European Union has enacted regulations regarding maximum nickel leaching in products that come into direct and prolonged contact with the skin, such regulations have not been implemented in Japan or the United States.¹¹ International e-commerce makes these grips widely available, even in regions where strict metal regulations are in place. As screen time increases, it is important to consider all phone-related exposures including components of the case, screen protector, and main device body.

Watches

Smart watches and fitness bands are widely available to consumers and serve a variety of health and lifestyle functions. Features include fitness tracking, notification management, mobile payment, electrocardiography, navigation, and sleep and oxygen sensors. Multiple companies have produced hand- and wrist-based sensors for detailed wellness tracking within these categories. Allergic contact dermatitis to smart watches and wristbands manifests as eczematous lesions on the wrist (dorsal,^21,22 volar,²⁰ or circumferential involvement^23,24).

(Meth)acrylates used to adhere screen protectors, house lithium ion batteries, and bind metal to plastic have been reported to cause ACD in smart watch users.^22,25 In addition, there are at least 2 published reports of ACD to nickel in Apple Watches.^21,31 Apple, having sold more than 229 million watches worldwide, has acknowledged the presence of trace acrylates and nickel in their watches (the latter falling below European Registration, Evaluation, Authorization, and Restriction of Chemicals limits).³² Hosoki et al²⁰ identified ACD resulting from chromium exposure in the clasp of an Apple Watch band, which remains unreported by the manufacturer as a potential allergen.

Continuous Glucose Monitors

Continuous glucose monitoring systems provide users with dynamic information on their glycemic status and are associated with lower glycated hemoglobin and reduced episodes of hypoglycemia in patients with diabetes.³³ Recently, growing interest in personalized health monitoring and performance optimization has expanded CGM use to individuals without diabetes; there are 2 over-the-counter CGM options currently available in the United States.³⁴

Allergic contact dermatitis to CGMs in patients with diabetes is well characterized, manifesting as pruritic acute or chronic dermatitis at the sensor site.²⁷ To date, we are unaware of published cases of ACD associated with use of CGM in individuals without diabetes; however, wearing a CGM during athletic activities and sweating could potentially increase adhesive degradation and/or penetration of allergens in the skin.⁶

Isobornyl acrylate, named the 2020 Allergen of the Year,³⁵ is the most well-known contact allergen in glucose sensors.^36,33 Initially suspected as a component of the CGM skin adhesive, isobornyl acrylate was found to leach from the device body onto the skin in users of one CGM device.³⁶ Other reported allergens in CGM devices include colophony and related rosin derivatives, ethyl cyanoacrylate, and several chemicals that are not available as commercial patch test substances.²⁷ Understanding these potential allergens is important for patch testing considerations as CGM use increases in individuals without diabetes.

Final Thoughts

Allergic contact dermatitis to personal electronic devices including wearables, sensors, and fitness trackers is an emerging problem that should be considered in cases of dermatitis of the wrists, hands, face, ears, or in any area that comes into contact with such devices. Although in-depth studies are lacking, certain wearable devices appear to introduce continuous, low-level allergen exposure that may be below the sensitization threshold but still is capable of eliciting ACD in previously sensitized users.^21,26 Furthermore, increased allergen exposure is facilitated by prolonged skin contact, mechanical friction, and sweat.

Comprehensive patch testing often is necessary to diagnose cases of ACD to personal electronic devices.³³ The thin-layer rapid use epicutaneous (T.R.U.E.) test does not include (meth)acrylates, which repeatedly have come up as culprit allergens.³⁷ Isobornyl acrylate, a key allergen related to CGMs, is absent from standard patch test series.²⁶ Nickel remains a common culprit in these devices despite adherence to European regulations.²¹ Since there is no obligation for manufacturers to declare all possible ingredients, chemical analysis can be useful in identifying potential allergens and directing the patch test strategy, but this is not feasible in general clinical practice outside the research setting.²

Following patch testing, patient education is essential to managing personal electronic device—induced ACD. Informed patients should switch to products that do not contain their triggers—although this may be more easily said than done, since incomplete ingredient disclosure from manufacturers may necessitate a frustrating and expensive trial-and-error approach. As wearable technology proliferates, device composition and potential contact allergen transparency must be prioritized by manufacturers and regulatory bodies. Until then, clinicians should stay on their toes regarding new and emerging clinical presentations and contact allergens in hopes of improving patient outcomes.

Personal electronic devices have become more common as consumer-driven health and entertainment practices continue to increase in popularity. A wide variety of devices including smartphones, headphones and earbuds, fitness watches, and continuous glucose monitors (CGMs) allow consumers to collect data and personalize their daily activities and health practices. The global market for fitness tracking devices alone was valued at $62.03 billion in 2024 and is projected to grow to $290.85 billion by 2032.¹ Accordingly, the growing demand for continuous data tracking has led to new and prolonged skin contact with these devices, which have become emerging sources of allergic contact dermatitis (ACD). In this article, we provide a summary of the potential allergenicity of personal electronic devices with a focus on wearable devices, including clinical manifestations, reported allergens, and patch testing and management considerations (Table^2-28).

Earbuds and Headphones

Wireless earbuds and headphones are used for listening to media and may contain microphones for voice calls. Earbuds are inserted into the ears while headphones are worn over the ears with a connecting band across the scalp. These devices frequently are worn during physical activity and thus in the setting of moist sweaty environments and mechanical friction on the skin. Depending on the style of the earbuds or headphones, associated ACD may manifest as acute or chronic pruritic eczema involving the inner and/or outer ears and potentially the periauricular areas or scalp.² In a reported case of earbud ACD, the patient first presented to an otolaryngologist before being referred to a dermatologist for further evaluation and patch testing.⁹ Clinicians may be unfamiliar with these devices as a source of ACD or may potentially overlook inner ear canal manifestations, which may delay diagnosis.

Allergens reported in earbuds include (meth)acrylates,^4-6 nickel, gold,⁸ and silicone.⁹ Apple AirPods and Samsung Galaxy Buds disclose the presence of acrylates and nickel.^5,6 Cases also have been reported of ACD to gold earbud microphones⁸ and unknown allergens within silicone tips.^4,9 Acrylates, named the 2012 Allergen of the Year by the American Contact Dermatitis Society,²⁹ are used in a wide variety of consumer products as adhesives and coatings and are among the most frequently suspected headphone allergens.⁴ While fully polymerized acrylates theoretically are nonallergenic, residual acrylic monomers are potent allergens that may be found in in these products due to incomplete curing or polymer breakdown.²⁹ It remains unclear whether earbud allergen concentrations are sufficient to induce sensitization or merely elicit ACD in previously sensitized users.²⁹ Among patients with earbud ACD, the finding of inconsistent patch test reactions/cross-reactions led to the hypothesis that these headphones may contain an unidentified proprietary (meth)acrylate.⁴

Headphones, often utilized by runners and gymgoers for their comfort and fit, also have gained recent attention for their unique allergen profiles. In 2024, a case series described primary sensitization to octylisothiazolinone causing severe headphone-related ACD.³ This preservative, which is in the same family as methylchloroisothiazolinone/methylisothiazolinone, is used as a biocide in the leather or faux leather that encases the foam padding of headphones.³ Another case report highlighted ACD caused by methylisothiazolinone, methylchloroisothiazolinone, and octylisothiazolinone present in various components of a pair of headphones.² These cases are notable, as European legislation limiting the use of methylchloroisothiazolinone/methylisothiazolinone in personal care products does not apply to inclusion of isothiazolinones in other product categories, such as detergents, paints, glues, and personal electronic devices.

Mobile Phones

Mobile phones are a staple in modern society, used for a multitude of tasks including communication, internet browsing, entertainment, and activity tracking. In the early 2000s, mobile phone ACD primarily manifested on the lateral face, ears, and periauricular regions,¹² as well as the thighs from carriage in pants pockets. Early cases of mobile phone ACD were attributed to metals including chromium¹⁶ and nickel.¹⁴ At that time, lengthy and frequent phone calls with the device against the ear were thought to increase exposure to metal allergens.³⁰ More recently, as the utility of these devices has evolved, ACD has been reported to manifest on the fingers and hands associated with contact with cell phone cases, accessories, and screen protectors (Figure). In one report, a 17-year-old boy with chronic eczema of the palms was diagnosed with ACD to the rubber-related chemicals paraphenylenediamine and N-cyclohexyl-N-phenyl-4-phenylenediamine, confirmed via chemical analysis to be present in a phone case the patient used during daily gaming.¹⁷ Similarly, another case of palmar ACD resulted from thiuram rubber accelerators in a phone case.¹⁸ Most recently, a Japanese patient with a history of skin reactions to costume jewelry developed ACD involving the proximal middle finger due to exposure to nickel in a ring-grip phone case.¹¹ While the European Union has enacted regulations regarding maximum nickel leaching in products that come into direct and prolonged contact with the skin, such regulations have not been implemented in Japan or the United States.¹¹ International e-commerce makes these grips widely available, even in regions where strict metal regulations are in place. As screen time increases, it is important to consider all phone-related exposures including components of the case, screen protector, and main device body.

Watches

Smart watches and fitness bands are widely available to consumers and serve a variety of health and lifestyle functions. Features include fitness tracking, notification management, mobile payment, electrocardiography, navigation, and sleep and oxygen sensors. Multiple companies have produced hand- and wrist-based sensors for detailed wellness tracking within these categories. Allergic contact dermatitis to smart watches and wristbands manifests as eczematous lesions on the wrist (dorsal,^21,22 volar,²⁰ or circumferential involvement^23,24).

(Meth)acrylates used to adhere screen protectors, house lithium ion batteries, and bind metal to plastic have been reported to cause ACD in smart watch users.^22,25 In addition, there are at least 2 published reports of ACD to nickel in Apple Watches.^21,31 Apple, having sold more than 229 million watches worldwide, has acknowledged the presence of trace acrylates and nickel in their watches (the latter falling below European Registration, Evaluation, Authorization, and Restriction of Chemicals limits).³² Hosoki et al²⁰ identified ACD resulting from chromium exposure in the clasp of an Apple Watch band, which remains unreported by the manufacturer as a potential allergen.

Continuous Glucose Monitors

Continuous glucose monitoring systems provide users with dynamic information on their glycemic status and are associated with lower glycated hemoglobin and reduced episodes of hypoglycemia in patients with diabetes.³³ Recently, growing interest in personalized health monitoring and performance optimization has expanded CGM use to individuals without diabetes; there are 2 over-the-counter CGM options currently available in the United States.³⁴

Allergic contact dermatitis to CGMs in patients with diabetes is well characterized, manifesting as pruritic acute or chronic dermatitis at the sensor site.²⁷ To date, we are unaware of published cases of ACD associated with use of CGM in individuals without diabetes; however, wearing a CGM during athletic activities and sweating could potentially increase adhesive degradation and/or penetration of allergens in the skin.⁶

Isobornyl acrylate, named the 2020 Allergen of the Year,³⁵ is the most well-known contact allergen in glucose sensors.^36,33 Initially suspected as a component of the CGM skin adhesive, isobornyl acrylate was found to leach from the device body onto the skin in users of one CGM device.³⁶ Other reported allergens in CGM devices include colophony and related rosin derivatives, ethyl cyanoacrylate, and several chemicals that are not available as commercial patch test substances.²⁷ Understanding these potential allergens is important for patch testing considerations as CGM use increases in individuals without diabetes.

Final Thoughts

Allergic contact dermatitis to personal electronic devices including wearables, sensors, and fitness trackers is an emerging problem that should be considered in cases of dermatitis of the wrists, hands, face, ears, or in any area that comes into contact with such devices. Although in-depth studies are lacking, certain wearable devices appear to introduce continuous, low-level allergen exposure that may be below the sensitization threshold but still is capable of eliciting ACD in previously sensitized users.^21,26 Furthermore, increased allergen exposure is facilitated by prolonged skin contact, mechanical friction, and sweat.

Comprehensive patch testing often is necessary to diagnose cases of ACD to personal electronic devices.³³ The thin-layer rapid use epicutaneous (T.R.U.E.) test does not include (meth)acrylates, which repeatedly have come up as culprit allergens.³⁷ Isobornyl acrylate, a key allergen related to CGMs, is absent from standard patch test series.²⁶ Nickel remains a common culprit in these devices despite adherence to European regulations.²¹ Since there is no obligation for manufacturers to declare all possible ingredients, chemical analysis can be useful in identifying potential allergens and directing the patch test strategy, but this is not feasible in general clinical practice outside the research setting.²

Following patch testing, patient education is essential to managing personal electronic device—induced ACD. Informed patients should switch to products that do not contain their triggers—although this may be more easily said than done, since incomplete ingredient disclosure from manufacturers may necessitate a frustrating and expensive trial-and-error approach. As wearable technology proliferates, device composition and potential contact allergen transparency must be prioritized by manufacturers and regulatory bodies. Until then, clinicians should stay on their toes regarding new and emerging clinical presentations and contact allergens in hopes of improving patient outcomes.

Personal electronic devices have become more common as consumer-driven health and entertainment practices continue to increase in popularity. A wide variety of devices including smartphones, headphones and earbuds, fitness watches, and continuous glucose monitors (CGMs) allow consumers to collect data and personalize their daily activities and health practices. The global market for fitness tracking devices alone was valued at $62.03 billion in 2024 and is projected to grow to $290.85 billion by 2032.¹ Accordingly, the growing demand for continuous data tracking has led to new and prolonged skin contact with these devices, which have become emerging sources of allergic contact dermatitis (ACD). In this article, we provide a summary of the potential allergenicity of personal electronic devices with a focus on wearable devices, including clinical manifestations, reported allergens, and patch testing and management considerations (Table^2-28).

Earbuds and Headphones

Wireless earbuds and headphones are used for listening to media and may contain microphones for voice calls. Earbuds are inserted into the ears while headphones are worn over the ears with a connecting band across the scalp. These devices frequently are worn during physical activity and thus in the setting of moist sweaty environments and mechanical friction on the skin. Depending on the style of the earbuds or headphones, associated ACD may manifest as acute or chronic pruritic eczema involving the inner and/or outer ears and potentially the periauricular areas or scalp.² In a reported case of earbud ACD, the patient first presented to an otolaryngologist before being referred to a dermatologist for further evaluation and patch testing.⁹ Clinicians may be unfamiliar with these devices as a source of ACD or may potentially overlook inner ear canal manifestations, which may delay diagnosis.

Allergens reported in earbuds include (meth)acrylates,^4-6 nickel, gold,⁸ and silicone.⁹ Apple AirPods and Samsung Galaxy Buds disclose the presence of acrylates and nickel.^5,6 Cases also have been reported of ACD to gold earbud microphones⁸ and unknown allergens within silicone tips.^4,9 Acrylates, named the 2012 Allergen of the Year by the American Contact Dermatitis Society,²⁹ are used in a wide variety of consumer products as adhesives and coatings and are among the most frequently suspected headphone allergens.⁴ While fully polymerized acrylates theoretically are nonallergenic, residual acrylic monomers are potent allergens that may be found in in these products due to incomplete curing or polymer breakdown.²⁹ It remains unclear whether earbud allergen concentrations are sufficient to induce sensitization or merely elicit ACD in previously sensitized users.²⁹ Among patients with earbud ACD, the finding of inconsistent patch test reactions/cross-reactions led to the hypothesis that these headphones may contain an unidentified proprietary (meth)acrylate.⁴

Headphones, often utilized by runners and gymgoers for their comfort and fit, also have gained recent attention for their unique allergen profiles. In 2024, a case series described primary sensitization to octylisothiazolinone causing severe headphone-related ACD.³ This preservative, which is in the same family as methylchloroisothiazolinone/methylisothiazolinone, is used as a biocide in the leather or faux leather that encases the foam padding of headphones.³ Another case report highlighted ACD caused by methylisothiazolinone, methylchloroisothiazolinone, and octylisothiazolinone present in various components of a pair of headphones.² These cases are notable, as European legislation limiting the use of methylchloroisothiazolinone/methylisothiazolinone in personal care products does not apply to inclusion of isothiazolinones in other product categories, such as detergents, paints, glues, and personal electronic devices.

Mobile Phones

Mobile phones are a staple in modern society, used for a multitude of tasks including communication, internet browsing, entertainment, and activity tracking. In the early 2000s, mobile phone ACD primarily manifested on the lateral face, ears, and periauricular regions,¹² as well as the thighs from carriage in pants pockets. Early cases of mobile phone ACD were attributed to metals including chromium¹⁶ and nickel.¹⁴ At that time, lengthy and frequent phone calls with the device against the ear were thought to increase exposure to metal allergens.³⁰ More recently, as the utility of these devices has evolved, ACD has been reported to manifest on the fingers and hands associated with contact with cell phone cases, accessories, and screen protectors (Figure). In one report, a 17-year-old boy with chronic eczema of the palms was diagnosed with ACD to the rubber-related chemicals paraphenylenediamine and N-cyclohexyl-N-phenyl-4-phenylenediamine, confirmed via chemical analysis to be present in a phone case the patient used during daily gaming.¹⁷ Similarly, another case of palmar ACD resulted from thiuram rubber accelerators in a phone case.¹⁸ Most recently, a Japanese patient with a history of skin reactions to costume jewelry developed ACD involving the proximal middle finger due to exposure to nickel in a ring-grip phone case.¹¹ While the European Union has enacted regulations regarding maximum nickel leaching in products that come into direct and prolonged contact with the skin, such regulations have not been implemented in Japan or the United States.¹¹ International e-commerce makes these grips widely available, even in regions where strict metal regulations are in place. As screen time increases, it is important to consider all phone-related exposures including components of the case, screen protector, and main device body.

Watches

Smart watches and fitness bands are widely available to consumers and serve a variety of health and lifestyle functions. Features include fitness tracking, notification management, mobile payment, electrocardiography, navigation, and sleep and oxygen sensors. Multiple companies have produced hand- and wrist-based sensors for detailed wellness tracking within these categories. Allergic contact dermatitis to smart watches and wristbands manifests as eczematous lesions on the wrist (dorsal,^21,22 volar,²⁰ or circumferential involvement^23,24).

(Meth)acrylates used to adhere screen protectors, house lithium ion batteries, and bind metal to plastic have been reported to cause ACD in smart watch users.^22,25 In addition, there are at least 2 published reports of ACD to nickel in Apple Watches.^21,31 Apple, having sold more than 229 million watches worldwide, has acknowledged the presence of trace acrylates and nickel in their watches (the latter falling below European Registration, Evaluation, Authorization, and Restriction of Chemicals limits).³² Hosoki et al²⁰ identified ACD resulting from chromium exposure in the clasp of an Apple Watch band, which remains unreported by the manufacturer as a potential allergen.

Continuous Glucose Monitors

Continuous glucose monitoring systems provide users with dynamic information on their glycemic status and are associated with lower glycated hemoglobin and reduced episodes of hypoglycemia in patients with diabetes.³³ Recently, growing interest in personalized health monitoring and performance optimization has expanded CGM use to individuals without diabetes; there are 2 over-the-counter CGM options currently available in the United States.³⁴

Allergic contact dermatitis to CGMs in patients with diabetes is well characterized, manifesting as pruritic acute or chronic dermatitis at the sensor site.²⁷ To date, we are unaware of published cases of ACD associated with use of CGM in individuals without diabetes; however, wearing a CGM during athletic activities and sweating could potentially increase adhesive degradation and/or penetration of allergens in the skin.⁶

Isobornyl acrylate, named the 2020 Allergen of the Year,³⁵ is the most well-known contact allergen in glucose sensors.^36,33 Initially suspected as a component of the CGM skin adhesive, isobornyl acrylate was found to leach from the device body onto the skin in users of one CGM device.³⁶ Other reported allergens in CGM devices include colophony and related rosin derivatives, ethyl cyanoacrylate, and several chemicals that are not available as commercial patch test substances.²⁷ Understanding these potential allergens is important for patch testing considerations as CGM use increases in individuals without diabetes.

Final Thoughts

Allergic contact dermatitis to personal electronic devices including wearables, sensors, and fitness trackers is an emerging problem that should be considered in cases of dermatitis of the wrists, hands, face, ears, or in any area that comes into contact with such devices. Although in-depth studies are lacking, certain wearable devices appear to introduce continuous, low-level allergen exposure that may be below the sensitization threshold but still is capable of eliciting ACD in previously sensitized users.^21,26 Furthermore, increased allergen exposure is facilitated by prolonged skin contact, mechanical friction, and sweat.

Comprehensive patch testing often is necessary to diagnose cases of ACD to personal electronic devices.³³ The thin-layer rapid use epicutaneous (T.R.U.E.) test does not include (meth)acrylates, which repeatedly have come up as culprit allergens.³⁷ Isobornyl acrylate, a key allergen related to CGMs, is absent from standard patch test series.²⁶ Nickel remains a common culprit in these devices despite adherence to European regulations.²¹ Since there is no obligation for manufacturers to declare all possible ingredients, chemical analysis can be useful in identifying potential allergens and directing the patch test strategy, but this is not feasible in general clinical practice outside the research setting.²

Following patch testing, patient education is essential to managing personal electronic device—induced ACD. Informed patients should switch to products that do not contain their triggers—although this may be more easily said than done, since incomplete ingredient disclosure from manufacturers may necessitate a frustrating and expensive trial-and-error approach. As wearable technology proliferates, device composition and potential contact allergen transparency must be prioritized by manufacturers and regulatory bodies. Until then, clinicians should stay on their toes regarding new and emerging clinical presentations and contact allergens in hopes of improving patient outcomes.

Practice Gap

Many dermatology practices utilize pens and markers to label biopsy specimen containers, but the ink may have variable susceptibility to fading and smearing when exposed to moisture before processing. Specimen containers often are placed in plastic bags for transport. If formalin accidentally spills into the bag during this time, the labels may be exposed to moisture for hours, overnight, or even over a weekend. Effective labeling with formalin-resistant ink is crucial for maintaining the clarity of anatomic location and planning treatment, especially when multiple samples are obtained.

The Technique

We tested 12 pens and markers commonly used when labeling specimen containers to determine their susceptibility to fading due to accidental formalin exposure (Figure). Various inks were allowed to dry on sample specimen labels for 5 minutes before a thin layer of 10% buffered formalin was evenly distributed over the dried ink. Photographs of the labels were taken at baseline as well as 15 minutes, 1 hour, 3 hours, and 24 hours after formalin exposure.

Fading was observed in both the skin marker and gel panes after 15 minutes and peaked after 1 hour. Gel pens were most susceptible to fading on exposure to formalin, and the level of fading varied by ink color, with certain colors disappearing almost entirely (Figure). The solvent-resistant marker had a robust defense to formalin, as did both ballpoint pens.

Practice Implications

Given our findings, dermatology practices should avoid using gel pens to label specimen containers. Solvent-resistant markers performed as expected; however, ballpoint pens appeared to withstand formalin exposure to a similar degree and often are more readily available. Labeling biopsy specimens with an appropriate ink ensures that each sample is clearly identified with the appropriate anatomic location and any other relevant patient information.

Practice Gap

Many dermatology practices utilize pens and markers to label biopsy specimen containers, but the ink may have variable susceptibility to fading and smearing when exposed to moisture before processing. Specimen containers often are placed in plastic bags for transport. If formalin accidentally spills into the bag during this time, the labels may be exposed to moisture for hours, overnight, or even over a weekend. Effective labeling with formalin-resistant ink is crucial for maintaining the clarity of anatomic location and planning treatment, especially when multiple samples are obtained.

The Technique

We tested 12 pens and markers commonly used when labeling specimen containers to determine their susceptibility to fading due to accidental formalin exposure (Figure). Various inks were allowed to dry on sample specimen labels for 5 minutes before a thin layer of 10% buffered formalin was evenly distributed over the dried ink. Photographs of the labels were taken at baseline as well as 15 minutes, 1 hour, 3 hours, and 24 hours after formalin exposure.

Fading was observed in both the skin marker and gel panes after 15 minutes and peaked after 1 hour. Gel pens were most susceptible to fading on exposure to formalin, and the level of fading varied by ink color, with certain colors disappearing almost entirely (Figure). The solvent-resistant marker had a robust defense to formalin, as did both ballpoint pens.

Practice Implications

Given our findings, dermatology practices should avoid using gel pens to label specimen containers. Solvent-resistant markers performed as expected; however, ballpoint pens appeared to withstand formalin exposure to a similar degree and often are more readily available. Labeling biopsy specimens with an appropriate ink ensures that each sample is clearly identified with the appropriate anatomic location and any other relevant patient information.

Practice Gap

Many dermatology practices utilize pens and markers to label biopsy specimen containers, but the ink may have variable susceptibility to fading and smearing when exposed to moisture before processing. Specimen containers often are placed in plastic bags for transport. If formalin accidentally spills into the bag during this time, the labels may be exposed to moisture for hours, overnight, or even over a weekend. Effective labeling with formalin-resistant ink is crucial for maintaining the clarity of anatomic location and planning treatment, especially when multiple samples are obtained.

The Technique

We tested 12 pens and markers commonly used when labeling specimen containers to determine their susceptibility to fading due to accidental formalin exposure (Figure). Various inks were allowed to dry on sample specimen labels for 5 minutes before a thin layer of 10% buffered formalin was evenly distributed over the dried ink. Photographs of the labels were taken at baseline as well as 15 minutes, 1 hour, 3 hours, and 24 hours after formalin exposure.

Fading was observed in both the skin marker and gel panes after 15 minutes and peaked after 1 hour. Gel pens were most susceptible to fading on exposure to formalin, and the level of fading varied by ink color, with certain colors disappearing almost entirely (Figure). The solvent-resistant marker had a robust defense to formalin, as did both ballpoint pens.

Practice Implications

Given our findings, dermatology practices should avoid using gel pens to label specimen containers. Solvent-resistant markers performed as expected; however, ballpoint pens appeared to withstand formalin exposure to a similar degree and often are more readily available. Labeling biopsy specimens with an appropriate ink ensures that each sample is clearly identified with the appropriate anatomic location and any other relevant patient information.

The umbrella term skin of color (SOC) includes individuals identifying as Black/African, Hispanic, Asian, Native American, Middle Eastern, and Mediterranean as well as multiracial groups. While the Fitzpatrick skin typing system is not an accurate proxy for describing skin tone, SOC populations typically correspond to Fitzpatrick skin types IV to VI, and clinical researchers often report the Fitzpatrick skin type of their study populations.¹

Over the past several decades, the underrepresentation of diverse skin tones in educational resources has limited clinical training.² For example, only 10.3% of conditions featured in contemporary dermatology textbooks are shown in darker skin tones.³ This educational resource gap has spurred a transformative movement toward inclusivity in dermatologic education, research, and clinical practice. Notable examples include VisualDx⁴ and Dermatology for Skin of Color.⁵ In addition, Cutis began publishing the Dx Across the Skin Color Spectrum fact sheet series in 2022 to highlight differences in how cutaneous conditions manifest in various skin tones (https://www.mdedge.com/cutis/dx-across-skin-color-spectrum).

These resources play a critical role in advancing dermatologic knowledge, ensuring that dermatologists and other health care professionals are well equipped to diagnose and treat dermatologic conditions in SOC populations with accuracy and cultural humility. These innovations also have enhanced our understanding of how common dermatologic conditions manifest and respond to treatment in SOC populations. Herein, we highlight advances in diagnostic and therapeutic approaches for the most common concerns among SOC populations in the United States, including acne vulgaris, atopic dermatitis (AD), seborrheic dermatitis (SD), melasma, postinflammatory hyperpigmentation, psoriasis, and seborrheic keratosis.

Chief Concerns Common Among SOC Populations in the United States

Acne Vulgaris—In patients with SOC, acne frequently results in pigmentary changes and scarring that can manifest as both hypertrophic and keloidal scars.⁶ Clinical evidence from randomized controlled studies supports the use of topical dapsone gel as a safe and effective frontline treatment for acne in patients with SOC.^7,8 Notably, the US Food and Drug Administration–approved 1726-nm laser with a contact-cooling sapphire window has demonstrated safety and efficacy in the management of acne across Fitzpatrick skin types II to VI.^9-11 To manage atrophic acne scars, cutting-edge laser and radiofrequency devices including erbium-doped yttrium aluminum garnet, fractional CO₂, and picosecond lasers have been effectively employed in SOC populations. When these energy-based treatments are combined with cooling systems, they substantially reduce the risk for thermal damage in darker skin tones.^12,13

Atopic Dermatitis—While epidemiologic data indicate that Black patients experience a higher prevalence (19.3%) of AD than Asian (17.8%), White (16.1%), or Hispanic (7.8%) groups in the United States, this disparity may be influenced by factors such as access to care and environmental stressors, which require further study.^14-16 The pathogenesis of AD involves a complex interaction between skin barrier dysfunction, immune dysregulation, and environmental triggers, with patients with SOC exhibiting distinct endotypes.^14,17 For example, East Asian individuals have elevated T_H17-related cytokines and a blended T_H17/T_H2 AD-psoriasis endotype,^14,18 while Black individuals have greater T_H2 skewing and filaggrin variations and higher serum IgE levels.¹⁷ Diagnostic advancements, including a modified Eczema Area and Severity Index using grayscale rather than erythema-based assessments for patients with SOC as well as a novel SOC dermatology atlas that includes AD have increased equity in disease evaluation.^19,20 Recent clinical trials support the efficacy of topical crisaborole, topical ruxolitinib, and biologics such as dupilumab, tralokinumab, lebrikizumab, and fezakinumab for AD in SOC populations, with dupilumab also improving postinflammatory hyperpigmentation.^20-22

Seborrheic Dermatitis—Seborrheic dermatitis is common in patients with SOC, though its manifestations vary by racial/ethnic background.²³ In Black patients, petaloid SD is more prevalent and can resemble secondary syphilis, making accurate diagnosis essential to rule out potential mimickers.²⁴ Effective treatments remain limited, as current therapies often fail to address both the underlying yeast-driven inflammation and the resulting pigmentary changes that commonly affect SOC populations.²⁵ Roflumilast foam 0.3%, a phosphodiesterase 4 inhibitor, has emerged as a promising option, offering both anti-inflammatory benefits and improvements in pigmentary alterations—making it particularly valuable for treatment of SD in patients with SOC.²⁶

Melasma—Melasma is more prevalent in women with darker skin types, particularly those of African descent and those from East and Southeast Asia or Latin America.^27,28 Standard treatments including hydroquinone, retinoids, azelaic acid, kojic acid, ascorbic acid, arbutin, alpha hydroxy acids, niacinamide, and the Kligman formula (5% hydroquinone, 0.1% tretinoin, and 0.1% dexamethasone) remain therapeutic foundations in patients with SOC.²⁹ Newer alternatives that are effective in SOC populations include topical metformin 30%30; topical isobutylamido thiazolyl resorcinol or thiamidol31; and tranexamic acid cream 5%, which has comparable efficacy to hydroquinone 4% with fewer adverse effects.³² Laser therapies such as the 675-nm and 1064-nm Q-switched neodymium-doped yttrium aluminum garnet lasers, offer effective pigment reduction and are safe in darker skin tones.^33,34

Postinflammatory Hyperpigmentation—Postinflammatory hyperpigmentation, often triggered by acne in SOC populations,²³ manifests as brown, tan, or gray discoloration and is managed using similar topical agents as melasma, with the 1927-nm laser providing an additional treatment option for patients with SOC.^27,35,36

Psoriasis—In patients with SOC, psoriasis often manifests with thicker plaques, increased scaling, and greater body surface area involvement, leading to considerable quality-of-life implications.³⁷ Although prevalence is highest in White populations (3.6%), Asian (2.5%) and Hispanic/Latino (1.9%) patients experience increased disease severity, potentially explaining why psoriasis is among the top chief complaints for these racial/ ethnic groups in the United States.^23,38 Greater diversity in clinical trials has improved our understanding of the efficacy of biologics for psoriasis in SOC populations. The VISIBLE trial—the first SOC-exclusive psoriasis trial—demonstrated a Psoriasis Area and Severity Index 90 response in 57.1% (44/77) of participants receiving guselkumab vs 3.8% (1/26) of participants receiving placebo by week 16 (P<.001).³⁹ Other biologics such as risankizumab, secukinumab, and brodalumab also have shown efficacy in SOC populations.^40-42 Additionally, topical therapies such as calcipotriene-betamethasone dipropionate cream/aerosol foam and halobetasol propionatetazarotene lotion have proven effective, with minimal adverse effects and low discontinuation rates in patients with SOC.^43-46

Seborrheic Keratosis—In SOC, seborrheic keratosis (SK) often appears as a variant known as dermatosis papulosa nigra (DPN), manifesting as small, benign, hyperpigmented papules, particularly on the face and neck.⁴⁷ Dermatosis papulosa nigra is common in Black, Hispanic, and some Asian populations, with variations in color and distribution among different racial/ethnic groups.⁴⁸ For example, in Korean populations, SKs commonly affect males, and in contrast to the dark brown color common in White populations, SKs in Korean patients often appear lighter brown or sometimes pink.⁴⁹ In contrast to the verrucous and stuck-on appearance often seen in White populations, South Asian populations more often have variants including pedunculated SKs, flat SKs, and stucco keratoses.⁵⁰ High-resolution dermoscopy improves differentiation from malignant lesions; however, a sudden SK eruption in any population warrants evaluation for underlying malignancy. Cryotherapy, though effective for removal of SKs, can cause pigmentary changes in SOC populations, making laser therapy and electrosurgery preferable for these patients due to the lower risk for pigmentary sequela. If hyperpigmentation occurs, topical treatments such as hydroquinone, tretinoin, or azelaic acid can help. New laser technologies and hydrogen-peroxide–based therapies offer safer and more effective removal options while minimizing pigmentary risks in SOC populations.^47,50 While DPNs are common in patients with darker skin tones, there are limited data on optimal treatment frequency, insurance coverage, and efficacy. This literature gap hinders our understanding of treatment accessibility and economic impact on our patients.⁵¹

Final Thoughts

Innovations such as standardized scoring systems and customized therapeutic strategies for conditions including acne, pigmentary disorders, and atopic dermatitis have markedly enhanced patient care and outcomes for the most common chief concerns in SOC populations. In addition, population-specific advancements have addressed unique diagnostic and therapeutic developments in Black, Asian/Pacific Islander, and Hispanic groups, from the nuanced presentations of atopic and seborrheic dermatitis in Black patients, to those of psoriasis in Asian/Pacific Islander and Hispanic populations. Finally, updated epidemiologic studies are essential to capture the current and evolving dermatologic concerns pertinent to patients with SOC, ensuring that future clinical and research efforts align with the unique needs of these populations.

The umbrella term skin of color (SOC) includes individuals identifying as Black/African, Hispanic, Asian, Native American, Middle Eastern, and Mediterranean as well as multiracial groups. While the Fitzpatrick skin typing system is not an accurate proxy for describing skin tone, SOC populations typically correspond to Fitzpatrick skin types IV to VI, and clinical researchers often report the Fitzpatrick skin type of their study populations.¹

Over the past several decades, the underrepresentation of diverse skin tones in educational resources has limited clinical training.² For example, only 10.3% of conditions featured in contemporary dermatology textbooks are shown in darker skin tones.³ This educational resource gap has spurred a transformative movement toward inclusivity in dermatologic education, research, and clinical practice. Notable examples include VisualDx⁴ and Dermatology for Skin of Color.⁵ In addition, Cutis began publishing the Dx Across the Skin Color Spectrum fact sheet series in 2022 to highlight differences in how cutaneous conditions manifest in various skin tones (https://www.mdedge.com/cutis/dx-across-skin-color-spectrum).

These resources play a critical role in advancing dermatologic knowledge, ensuring that dermatologists and other health care professionals are well equipped to diagnose and treat dermatologic conditions in SOC populations with accuracy and cultural humility. These innovations also have enhanced our understanding of how common dermatologic conditions manifest and respond to treatment in SOC populations. Herein, we highlight advances in diagnostic and therapeutic approaches for the most common concerns among SOC populations in the United States, including acne vulgaris, atopic dermatitis (AD), seborrheic dermatitis (SD), melasma, postinflammatory hyperpigmentation, psoriasis, and seborrheic keratosis.

Chief Concerns Common Among SOC Populations in the United States

Acne Vulgaris—In patients with SOC, acne frequently results in pigmentary changes and scarring that can manifest as both hypertrophic and keloidal scars.⁶ Clinical evidence from randomized controlled studies supports the use of topical dapsone gel as a safe and effective frontline treatment for acne in patients with SOC.^7,8 Notably, the US Food and Drug Administration–approved 1726-nm laser with a contact-cooling sapphire window has demonstrated safety and efficacy in the management of acne across Fitzpatrick skin types II to VI.^9-11 To manage atrophic acne scars, cutting-edge laser and radiofrequency devices including erbium-doped yttrium aluminum garnet, fractional CO₂, and picosecond lasers have been effectively employed in SOC populations. When these energy-based treatments are combined with cooling systems, they substantially reduce the risk for thermal damage in darker skin tones.^12,13

Atopic Dermatitis—While epidemiologic data indicate that Black patients experience a higher prevalence (19.3%) of AD than Asian (17.8%), White (16.1%), or Hispanic (7.8%) groups in the United States, this disparity may be influenced by factors such as access to care and environmental stressors, which require further study.^14-16 The pathogenesis of AD involves a complex interaction between skin barrier dysfunction, immune dysregulation, and environmental triggers, with patients with SOC exhibiting distinct endotypes.^14,17 For example, East Asian individuals have elevated T_H17-related cytokines and a blended T_H17/T_H2 AD-psoriasis endotype,^14,18 while Black individuals have greater T_H2 skewing and filaggrin variations and higher serum IgE levels.¹⁷ Diagnostic advancements, including a modified Eczema Area and Severity Index using grayscale rather than erythema-based assessments for patients with SOC as well as a novel SOC dermatology atlas that includes AD have increased equity in disease evaluation.^19,20 Recent clinical trials support the efficacy of topical crisaborole, topical ruxolitinib, and biologics such as dupilumab, tralokinumab, lebrikizumab, and fezakinumab for AD in SOC populations, with dupilumab also improving postinflammatory hyperpigmentation.^20-22

Seborrheic Dermatitis—Seborrheic dermatitis is common in patients with SOC, though its manifestations vary by racial/ethnic background.²³ In Black patients, petaloid SD is more prevalent and can resemble secondary syphilis, making accurate diagnosis essential to rule out potential mimickers.²⁴ Effective treatments remain limited, as current therapies often fail to address both the underlying yeast-driven inflammation and the resulting pigmentary changes that commonly affect SOC populations.²⁵ Roflumilast foam 0.3%, a phosphodiesterase 4 inhibitor, has emerged as a promising option, offering both anti-inflammatory benefits and improvements in pigmentary alterations—making it particularly valuable for treatment of SD in patients with SOC.²⁶

Melasma—Melasma is more prevalent in women with darker skin types, particularly those of African descent and those from East and Southeast Asia or Latin America.^27,28 Standard treatments including hydroquinone, retinoids, azelaic acid, kojic acid, ascorbic acid, arbutin, alpha hydroxy acids, niacinamide, and the Kligman formula (5% hydroquinone, 0.1% tretinoin, and 0.1% dexamethasone) remain therapeutic foundations in patients with SOC.²⁹ Newer alternatives that are effective in SOC populations include topical metformin 30%30; topical isobutylamido thiazolyl resorcinol or thiamidol31; and tranexamic acid cream 5%, which has comparable efficacy to hydroquinone 4% with fewer adverse effects.³² Laser therapies such as the 675-nm and 1064-nm Q-switched neodymium-doped yttrium aluminum garnet lasers, offer effective pigment reduction and are safe in darker skin tones.^33,34

Postinflammatory Hyperpigmentation—Postinflammatory hyperpigmentation, often triggered by acne in SOC populations,²³ manifests as brown, tan, or gray discoloration and is managed using similar topical agents as melasma, with the 1927-nm laser providing an additional treatment option for patients with SOC.^27,35,36

Psoriasis—In patients with SOC, psoriasis often manifests with thicker plaques, increased scaling, and greater body surface area involvement, leading to considerable quality-of-life implications.³⁷ Although prevalence is highest in White populations (3.6%), Asian (2.5%) and Hispanic/Latino (1.9%) patients experience increased disease severity, potentially explaining why psoriasis is among the top chief complaints for these racial/ ethnic groups in the United States.^23,38 Greater diversity in clinical trials has improved our understanding of the efficacy of biologics for psoriasis in SOC populations. The VISIBLE trial—the first SOC-exclusive psoriasis trial—demonstrated a Psoriasis Area and Severity Index 90 response in 57.1% (44/77) of participants receiving guselkumab vs 3.8% (1/26) of participants receiving placebo by week 16 (P<.001).³⁹ Other biologics such as risankizumab, secukinumab, and brodalumab also have shown efficacy in SOC populations.^40-42 Additionally, topical therapies such as calcipotriene-betamethasone dipropionate cream/aerosol foam and halobetasol propionatetazarotene lotion have proven effective, with minimal adverse effects and low discontinuation rates in patients with SOC.^43-46

Seborrheic Keratosis—In SOC, seborrheic keratosis (SK) often appears as a variant known as dermatosis papulosa nigra (DPN), manifesting as small, benign, hyperpigmented papules, particularly on the face and neck.⁴⁷ Dermatosis papulosa nigra is common in Black, Hispanic, and some Asian populations, with variations in color and distribution among different racial/ethnic groups.⁴⁸ For example, in Korean populations, SKs commonly affect males, and in contrast to the dark brown color common in White populations, SKs in Korean patients often appear lighter brown or sometimes pink.⁴⁹ In contrast to the verrucous and stuck-on appearance often seen in White populations, South Asian populations more often have variants including pedunculated SKs, flat SKs, and stucco keratoses.⁵⁰ High-resolution dermoscopy improves differentiation from malignant lesions; however, a sudden SK eruption in any population warrants evaluation for underlying malignancy. Cryotherapy, though effective for removal of SKs, can cause pigmentary changes in SOC populations, making laser therapy and electrosurgery preferable for these patients due to the lower risk for pigmentary sequela. If hyperpigmentation occurs, topical treatments such as hydroquinone, tretinoin, or azelaic acid can help. New laser technologies and hydrogen-peroxide–based therapies offer safer and more effective removal options while minimizing pigmentary risks in SOC populations.^47,50 While DPNs are common in patients with darker skin tones, there are limited data on optimal treatment frequency, insurance coverage, and efficacy. This literature gap hinders our understanding of treatment accessibility and economic impact on our patients.⁵¹

Final Thoughts

Innovations such as standardized scoring systems and customized therapeutic strategies for conditions including acne, pigmentary disorders, and atopic dermatitis have markedly enhanced patient care and outcomes for the most common chief concerns in SOC populations. In addition, population-specific advancements have addressed unique diagnostic and therapeutic developments in Black, Asian/Pacific Islander, and Hispanic groups, from the nuanced presentations of atopic and seborrheic dermatitis in Black patients, to those of psoriasis in Asian/Pacific Islander and Hispanic populations. Finally, updated epidemiologic studies are essential to capture the current and evolving dermatologic concerns pertinent to patients with SOC, ensuring that future clinical and research efforts align with the unique needs of these populations.

The umbrella term skin of color (SOC) includes individuals identifying as Black/African, Hispanic, Asian, Native American, Middle Eastern, and Mediterranean as well as multiracial groups. While the Fitzpatrick skin typing system is not an accurate proxy for describing skin tone, SOC populations typically correspond to Fitzpatrick skin types IV to VI, and clinical researchers often report the Fitzpatrick skin type of their study populations.¹

Over the past several decades, the underrepresentation of diverse skin tones in educational resources has limited clinical training.² For example, only 10.3% of conditions featured in contemporary dermatology textbooks are shown in darker skin tones.³ This educational resource gap has spurred a transformative movement toward inclusivity in dermatologic education, research, and clinical practice. Notable examples include VisualDx⁴ and Dermatology for Skin of Color.⁵ In addition, Cutis began publishing the Dx Across the Skin Color Spectrum fact sheet series in 2022 to highlight differences in how cutaneous conditions manifest in various skin tones (https://www.mdedge.com/cutis/dx-across-skin-color-spectrum).

These resources play a critical role in advancing dermatologic knowledge, ensuring that dermatologists and other health care professionals are well equipped to diagnose and treat dermatologic conditions in SOC populations with accuracy and cultural humility. These innovations also have enhanced our understanding of how common dermatologic conditions manifest and respond to treatment in SOC populations. Herein, we highlight advances in diagnostic and therapeutic approaches for the most common concerns among SOC populations in the United States, including acne vulgaris, atopic dermatitis (AD), seborrheic dermatitis (SD), melasma, postinflammatory hyperpigmentation, psoriasis, and seborrheic keratosis.

Chief Concerns Common Among SOC Populations in the United States

Acne Vulgaris—In patients with SOC, acne frequently results in pigmentary changes and scarring that can manifest as both hypertrophic and keloidal scars.⁶ Clinical evidence from randomized controlled studies supports the use of topical dapsone gel as a safe and effective frontline treatment for acne in patients with SOC.^7,8 Notably, the US Food and Drug Administration–approved 1726-nm laser with a contact-cooling sapphire window has demonstrated safety and efficacy in the management of acne across Fitzpatrick skin types II to VI.^9-11 To manage atrophic acne scars, cutting-edge laser and radiofrequency devices including erbium-doped yttrium aluminum garnet, fractional CO₂, and picosecond lasers have been effectively employed in SOC populations. When these energy-based treatments are combined with cooling systems, they substantially reduce the risk for thermal damage in darker skin tones.^12,13

Atopic Dermatitis—While epidemiologic data indicate that Black patients experience a higher prevalence (19.3%) of AD than Asian (17.8%), White (16.1%), or Hispanic (7.8%) groups in the United States, this disparity may be influenced by factors such as access to care and environmental stressors, which require further study.^14-16 The pathogenesis of AD involves a complex interaction between skin barrier dysfunction, immune dysregulation, and environmental triggers, with patients with SOC exhibiting distinct endotypes.^14,17 For example, East Asian individuals have elevated T_H17-related cytokines and a blended T_H17/T_H2 AD-psoriasis endotype,^14,18 while Black individuals have greater T_H2 skewing and filaggrin variations and higher serum IgE levels.¹⁷ Diagnostic advancements, including a modified Eczema Area and Severity Index using grayscale rather than erythema-based assessments for patients with SOC as well as a novel SOC dermatology atlas that includes AD have increased equity in disease evaluation.^19,20 Recent clinical trials support the efficacy of topical crisaborole, topical ruxolitinib, and biologics such as dupilumab, tralokinumab, lebrikizumab, and fezakinumab for AD in SOC populations, with dupilumab also improving postinflammatory hyperpigmentation.^20-22

Seborrheic Dermatitis—Seborrheic dermatitis is common in patients with SOC, though its manifestations vary by racial/ethnic background.²³ In Black patients, petaloid SD is more prevalent and can resemble secondary syphilis, making accurate diagnosis essential to rule out potential mimickers.²⁴ Effective treatments remain limited, as current therapies often fail to address both the underlying yeast-driven inflammation and the resulting pigmentary changes that commonly affect SOC populations.²⁵ Roflumilast foam 0.3%, a phosphodiesterase 4 inhibitor, has emerged as a promising option, offering both anti-inflammatory benefits and improvements in pigmentary alterations—making it particularly valuable for treatment of SD in patients with SOC.²⁶

Melasma—Melasma is more prevalent in women with darker skin types, particularly those of African descent and those from East and Southeast Asia or Latin America.^27,28 Standard treatments including hydroquinone, retinoids, azelaic acid, kojic acid, ascorbic acid, arbutin, alpha hydroxy acids, niacinamide, and the Kligman formula (5% hydroquinone, 0.1% tretinoin, and 0.1% dexamethasone) remain therapeutic foundations in patients with SOC.²⁹ Newer alternatives that are effective in SOC populations include topical metformin 30%30; topical isobutylamido thiazolyl resorcinol or thiamidol31; and tranexamic acid cream 5%, which has comparable efficacy to hydroquinone 4% with fewer adverse effects.³² Laser therapies such as the 675-nm and 1064-nm Q-switched neodymium-doped yttrium aluminum garnet lasers, offer effective pigment reduction and are safe in darker skin tones.^33,34

Postinflammatory Hyperpigmentation—Postinflammatory hyperpigmentation, often triggered by acne in SOC populations,²³ manifests as brown, tan, or gray discoloration and is managed using similar topical agents as melasma, with the 1927-nm laser providing an additional treatment option for patients with SOC.^27,35,36

Psoriasis—In patients with SOC, psoriasis often manifests with thicker plaques, increased scaling, and greater body surface area involvement, leading to considerable quality-of-life implications.³⁷ Although prevalence is highest in White populations (3.6%), Asian (2.5%) and Hispanic/Latino (1.9%) patients experience increased disease severity, potentially explaining why psoriasis is among the top chief complaints for these racial/ ethnic groups in the United States.^23,38 Greater diversity in clinical trials has improved our understanding of the efficacy of biologics for psoriasis in SOC populations. The VISIBLE trial—the first SOC-exclusive psoriasis trial—demonstrated a Psoriasis Area and Severity Index 90 response in 57.1% (44/77) of participants receiving guselkumab vs 3.8% (1/26) of participants receiving placebo by week 16 (P<.001).³⁹ Other biologics such as risankizumab, secukinumab, and brodalumab also have shown efficacy in SOC populations.^40-42 Additionally, topical therapies such as calcipotriene-betamethasone dipropionate cream/aerosol foam and halobetasol propionatetazarotene lotion have proven effective, with minimal adverse effects and low discontinuation rates in patients with SOC.^43-46

Seborrheic Keratosis—In SOC, seborrheic keratosis (SK) often appears as a variant known as dermatosis papulosa nigra (DPN), manifesting as small, benign, hyperpigmented papules, particularly on the face and neck.⁴⁷ Dermatosis papulosa nigra is common in Black, Hispanic, and some Asian populations, with variations in color and distribution among different racial/ethnic groups.⁴⁸ For example, in Korean populations, SKs commonly affect males, and in contrast to the dark brown color common in White populations, SKs in Korean patients often appear lighter brown or sometimes pink.⁴⁹ In contrast to the verrucous and stuck-on appearance often seen in White populations, South Asian populations more often have variants including pedunculated SKs, flat SKs, and stucco keratoses.⁵⁰ High-resolution dermoscopy improves differentiation from malignant lesions; however, a sudden SK eruption in any population warrants evaluation for underlying malignancy. Cryotherapy, though effective for removal of SKs, can cause pigmentary changes in SOC populations, making laser therapy and electrosurgery preferable for these patients due to the lower risk for pigmentary sequela. If hyperpigmentation occurs, topical treatments such as hydroquinone, tretinoin, or azelaic acid can help. New laser technologies and hydrogen-peroxide–based therapies offer safer and more effective removal options while minimizing pigmentary risks in SOC populations.^47,50 While DPNs are common in patients with darker skin tones, there are limited data on optimal treatment frequency, insurance coverage, and efficacy. This literature gap hinders our understanding of treatment accessibility and economic impact on our patients.⁵¹

Final Thoughts

Innovations such as standardized scoring systems and customized therapeutic strategies for conditions including acne, pigmentary disorders, and atopic dermatitis have markedly enhanced patient care and outcomes for the most common chief concerns in SOC populations. In addition, population-specific advancements have addressed unique diagnostic and therapeutic developments in Black, Asian/Pacific Islander, and Hispanic groups, from the nuanced presentations of atopic and seborrheic dermatitis in Black patients, to those of psoriasis in Asian/Pacific Islander and Hispanic populations. Finally, updated epidemiologic studies are essential to capture the current and evolving dermatologic concerns pertinent to patients with SOC, ensuring that future clinical and research efforts align with the unique needs of these populations.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening conditions that involve widespread necrosis of the skin and mucous membranes.¹ Guidelines for SJS and TEN recommend management in hospitals with access to inpatient dermatology to provide immediate interventions that are necessary for achieving optimal patient outcomes.² A delay in admission of 5 days or more after onset of symptoms has been associated with increases in overall mortality, bacteremia, intensive care unit (ICU) admission, and length of stay.³ Patients who are not directly admitted to specialized facilities and require transfer from other hospitals may experience delays in receiving critical interventions, further increasing the risk for mortality and complications. In this study, we analyzed the clinical outcomes of patients with SJS/TEN in relation to their admission pathway.

Methods

A single-center retrospective chart review was performed at Atrium Health Wake Forest Baptist Medical Center (AHWFBMC) in Winston-Salem, North Carolina. Participants were identified using i2b2, an informatics tool compliant with the Health Insurance Portability and Accountability Act for integrating biology and the bedside. Inclusion criteria were having a diagnosis of SJS (International Classification of Diseases, Tenth Revision, code L51.1; International Classification of Diseases, Ninth Revision, code 695.13), TEN (International Classification of Diseases, Tenth Revision, code L51.2; International Classification of Diseases, Ninth Revision, code 695.15) or Lyell syndrome from January 2012 to December 2024. Patients with erythema multiforme or bullous drug eruption were excluded, as these conditions initially were misdiagnosed as SJS or TEN. Patients with only a reported history of prior SJS or TEN also were excluded.

The following clinical outcomes were assessed: demographics, comorbidities, age at disease onset, outside hospital transfer status, complications during admission, inpatient length of stay in days, age of mortality (if applicable), culprit medications, interventions received, Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) upon admission, site of admission (eg, floor bed, ICU, medical ICU, burn unit), and length of disease process prior to hospital admission. Patients then were categorized as either direct or transfer admissions based on the initial point of care and admission process. Direct admissions included patients who presented to the AHWFBMC emergency department and were subsequently admitted. Transfer patients included patients who initially presented to an outside hospital and were transferred to AHWFBMC. Data regarding the wait time for Physician Access Line requests and the time elapsed from the initial transfer call to arrival at the tertiary hospital also were collected—this is a method that outside hospitals can use to contact physicians at the tertiary hospital for a possible transfer. Statistical analysis was performed using unpaired t tests and X² tests as necessary using GraphPad By Dotmatics Prism.

Results

A total of 112 patients were included in the analysis; of these, 71 had a diagnosis with biopsy confirmation of SJS, SJS/TEN overlap, or TEN (Table 1). Forty-one patients were excluded due to having a diagnosis of erythema multiforme or bullous drug eruption or a reported history of prior SJS or TEN without hospitalization. All biopsies were performed at AHWFBMC. Of the 71 confirmed patients with SJS/TEN, 54 (76%) were female with a mean age of 44 years. The majority of patients identified as Black (35 [49%]) or White (27 [38%]), along with Asian (7 [10%]) and other (2 [3%]). The most common comorbidity was cardiovascular disease in 42 (59%) patients, followed by type 2 diabetes in 36 (51%) patients. Among these 71 patients with SJS/TEN, 29 (41%) were directly admitted to the tertiary hospital, while 42 (59%) were transferred from outside hospitals.

Of the 71 confirmed patients with SJS/TEN, sulfonamides were identified as the most common inciting drug in 25 (41%) patients, followed by beta-lactam antibiotics in 16 (23%) patients (Table 2). This is consistent with previous literature of sulfamethoxazole with trimethoprim as the primary causative drug for SJS and TEN in the United States.¹

Clinical Outcomes—Of the 71 patients, there were 23 (32%) cases of SJS, 29 (41%) cases of SJS/TEN overlap, and 19 (27%) cases of TEN (eTable). The initial and maximum affected body surface area (BSA) was higher in transfer admissions, with a mean maximum BSA of 38.55% in the transfer group compared to 19.14% in the direct admissions. The mean SCORTEN (range, 0-5) was 1.6 overall, with a higher mean score of 1.92 in the transfer group compared to 1.07 in the direct admissions.

Transfer patients had a longer mean stay at the tertiary hospital (13.71 d) compared to direct admissions (7.17 d). The mean time from symptom onset until tertiary hospital admission was 8.5 days; transfer and direct admission patients had similar mean time from symptom onset of 9.02 days and 7.86 days, respectively. Although the duration of cutaneous symptoms from onset until tertiary hospital admission was similar (P=.283) between direct admissions (7.86 d) and transfer patients (9.02 d), the transfer group presented with greater disease severity at the time of admission. Transfer patients had a higher mean maximum BSA involvement (38.55% vs 19.14% [P=.005]), elevated SCORTEN (1.92 vs 1.07 [P=.029]), and longer mean hospital stays (13.71 d vs 7.17 d [P<.0001]) compared to direct admissions.

Despite the absence of mortality in both groups, transfer patients showed a higher number of ICU admissions (19 vs 5 [P=.014]) and burn unit admissions (9 vs 2 [P=.096]), bacteremia (16 vs 4 [P=.025]), acute kidney injury (13 vs 10 [P=.755]), acute respiratory failure (12 vs 5 [P=.272]), and transaminitis (8 vs 3 [P=.319]).

Outside Hospital Treatments—All outside hospitals provided supportive care with intravenous fluids and acetaminophen; however, further care provided at outside hospitals varied (Table 3), with transfer patients most frequently being treated with diphenhydramine (69% [29/42]), antimicrobial medications (57% [24/42]), steroids (40%), and epinephrine (10% [4/42]). Some patients may have received more than one of these treatments. Based on outside hospital treatments, the primary care teams’ main clinical concerns were allergic reactions and infection, as 33 (79%) patients received diphenhydramine (29 [89%]) or epinephrine (4 [12%]) and 24 (52%) received antimicrobial medications. Of the 42 transfer patients, 24 (57%) received or continued these medications before transfer; the medications were promptly discontinued upon tertiary hospital admission.

Once the outside hospitals contacted the tertiary hospital for a referral, the mean length of time between the transfer request and Physician Access Line call was 17.13 minutes (Table 4). Following the transfer request, the mean length of time for arrival at the tertiary hospital was 6.22 hours. The mean length of stay at the outside hospital prior to the patient being transferred was 3.84 days.

Comment

This retrospective study examined 71 patients with biopsy-confirmed SJS, SJS/TEN overlap, or TEN to evaluate differences in clinical outcomes between direct and transfer admissions. Transfer patients had a higher mean maximum affected BSA (38.55% vs 19.14% [P=.005]) and elevated SCORTEN (1.92 vs 1.07 [P=.029]); a higher number of transfer patients were admitted to the ICU (19 vs 5 [P=.014]) and burn unit (9 vs 2 [P=.096]), and this group also demonstrated longer hospitalization stays (13.71 vs 7.17 [P<.0001]). There were more complications among transfer patients, including bacteremia (16 vs 4 [P=.025]), which is consistent with findings from the existing literature.³

Once the decision for transfer of the patients included in our study was initiated and accepted, there was a prompt response and transfer of care; the mean length of time for Physician Access Line request was 17.13 minutes, and the mean transfer time to arrive at the tertiary hospital was 6.22 hours; however, patients spent an average of 3.84 days at outside hospitals, reflecting that transfer calls frequently were initiated due to urgent clinical decline of the patient rather than as an early intervention strategy. The management at outside hospitals often included the continuation of antimicrobial medications, which were discontinued upon transfer to AHWFBMC. Causative agents were either previously prescribed for a new medical condition or initiated for the management of suspected infections at outside hospitals. This may reflect the difficulty in correctly diagnosing SJS/TEN and initiating appropriate management at hospital facilities without an inpatient dermatologist.

The presence of inpatient dermatologists can improve the diagnostic accuracy and treatment of various conditions.^4,5 Dermatology consultations added or changed 77% of treatment plans for 271 hospitalized patients.⁴ The impact of this intervention is reflected by the success of early dermatology consultations in reducing the length of hospitalization and use of inappropriate treatments in the care of skin diseases.^6-8

Access to dermatologic care has been an identified need in inpatient hospitals that may limit the ability of hospitals to promptly treat serious conditions such as SJS/TEN.⁹ From an inpatient dermatology study from 2013 through 2019, 98.2% of 782 inpatient dermatologists reside in metropolitan areas, limiting the availability of care for rural patients; this study also found a decreasing number of facilities with inpatient dermatologists.¹⁰

The limitations of our study include a small sample size of 71 patients, which restricted the generalizability of our results. Our study also was based at a single tertiary center, which thereby limited the findings to this geographic area. It also was difficult to match patients by their demographic and comorbid conditions. The retrospective study design depended on the accuracy and completeness of medical records, which can introduce information bias. Future studies should compare the clinical outcomes of SJS/TEN based on burn unit and ICU admissions.

Conclusion

Prompt identification of SJS/TEN and rapid transfer to hospitals with inpatient dermatology are essential to optimize patient outcomes. Developing and validating SJS/TEN diagnosis and transfer protocols across multiple institutions may be helpful.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening conditions that involve widespread necrosis of the skin and mucous membranes.¹ Guidelines for SJS and TEN recommend management in hospitals with access to inpatient dermatology to provide immediate interventions that are necessary for achieving optimal patient outcomes.² A delay in admission of 5 days or more after onset of symptoms has been associated with increases in overall mortality, bacteremia, intensive care unit (ICU) admission, and length of stay.³ Patients who are not directly admitted to specialized facilities and require transfer from other hospitals may experience delays in receiving critical interventions, further increasing the risk for mortality and complications. In this study, we analyzed the clinical outcomes of patients with SJS/TEN in relation to their admission pathway.

Methods

A single-center retrospective chart review was performed at Atrium Health Wake Forest Baptist Medical Center (AHWFBMC) in Winston-Salem, North Carolina. Participants were identified using i2b2, an informatics tool compliant with the Health Insurance Portability and Accountability Act for integrating biology and the bedside. Inclusion criteria were having a diagnosis of SJS (International Classification of Diseases, Tenth Revision, code L51.1; International Classification of Diseases, Ninth Revision, code 695.13), TEN (International Classification of Diseases, Tenth Revision, code L51.2; International Classification of Diseases, Ninth Revision, code 695.15) or Lyell syndrome from January 2012 to December 2024. Patients with erythema multiforme or bullous drug eruption were excluded, as these conditions initially were misdiagnosed as SJS or TEN. Patients with only a reported history of prior SJS or TEN also were excluded.

The following clinical outcomes were assessed: demographics, comorbidities, age at disease onset, outside hospital transfer status, complications during admission, inpatient length of stay in days, age of mortality (if applicable), culprit medications, interventions received, Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) upon admission, site of admission (eg, floor bed, ICU, medical ICU, burn unit), and length of disease process prior to hospital admission. Patients then were categorized as either direct or transfer admissions based on the initial point of care and admission process. Direct admissions included patients who presented to the AHWFBMC emergency department and were subsequently admitted. Transfer patients included patients who initially presented to an outside hospital and were transferred to AHWFBMC. Data regarding the wait time for Physician Access Line requests and the time elapsed from the initial transfer call to arrival at the tertiary hospital also were collected—this is a method that outside hospitals can use to contact physicians at the tertiary hospital for a possible transfer. Statistical analysis was performed using unpaired t tests and X² tests as necessary using GraphPad By Dotmatics Prism.

Results

A total of 112 patients were included in the analysis; of these, 71 had a diagnosis with biopsy confirmation of SJS, SJS/TEN overlap, or TEN (Table 1). Forty-one patients were excluded due to having a diagnosis of erythema multiforme or bullous drug eruption or a reported history of prior SJS or TEN without hospitalization. All biopsies were performed at AHWFBMC. Of the 71 confirmed patients with SJS/TEN, 54 (76%) were female with a mean age of 44 years. The majority of patients identified as Black (35 [49%]) or White (27 [38%]), along with Asian (7 [10%]) and other (2 [3%]). The most common comorbidity was cardiovascular disease in 42 (59%) patients, followed by type 2 diabetes in 36 (51%) patients. Among these 71 patients with SJS/TEN, 29 (41%) were directly admitted to the tertiary hospital, while 42 (59%) were transferred from outside hospitals.

Of the 71 confirmed patients with SJS/TEN, sulfonamides were identified as the most common inciting drug in 25 (41%) patients, followed by beta-lactam antibiotics in 16 (23%) patients (Table 2). This is consistent with previous literature of sulfamethoxazole with trimethoprim as the primary causative drug for SJS and TEN in the United States.¹

Clinical Outcomes—Of the 71 patients, there were 23 (32%) cases of SJS, 29 (41%) cases of SJS/TEN overlap, and 19 (27%) cases of TEN (eTable). The initial and maximum affected body surface area (BSA) was higher in transfer admissions, with a mean maximum BSA of 38.55% in the transfer group compared to 19.14% in the direct admissions. The mean SCORTEN (range, 0-5) was 1.6 overall, with a higher mean score of 1.92 in the transfer group compared to 1.07 in the direct admissions.

Transfer patients had a longer mean stay at the tertiary hospital (13.71 d) compared to direct admissions (7.17 d). The mean time from symptom onset until tertiary hospital admission was 8.5 days; transfer and direct admission patients had similar mean time from symptom onset of 9.02 days and 7.86 days, respectively. Although the duration of cutaneous symptoms from onset until tertiary hospital admission was similar (P=.283) between direct admissions (7.86 d) and transfer patients (9.02 d), the transfer group presented with greater disease severity at the time of admission. Transfer patients had a higher mean maximum BSA involvement (38.55% vs 19.14% [P=.005]), elevated SCORTEN (1.92 vs 1.07 [P=.029]), and longer mean hospital stays (13.71 d vs 7.17 d [P<.0001]) compared to direct admissions.

Despite the absence of mortality in both groups, transfer patients showed a higher number of ICU admissions (19 vs 5 [P=.014]) and burn unit admissions (9 vs 2 [P=.096]), bacteremia (16 vs 4 [P=.025]), acute kidney injury (13 vs 10 [P=.755]), acute respiratory failure (12 vs 5 [P=.272]), and transaminitis (8 vs 3 [P=.319]).

Outside Hospital Treatments—All outside hospitals provided supportive care with intravenous fluids and acetaminophen; however, further care provided at outside hospitals varied (Table 3), with transfer patients most frequently being treated with diphenhydramine (69% [29/42]), antimicrobial medications (57% [24/42]), steroids (40%), and epinephrine (10% [4/42]). Some patients may have received more than one of these treatments. Based on outside hospital treatments, the primary care teams’ main clinical concerns were allergic reactions and infection, as 33 (79%) patients received diphenhydramine (29 [89%]) or epinephrine (4 [12%]) and 24 (52%) received antimicrobial medications. Of the 42 transfer patients, 24 (57%) received or continued these medications before transfer; the medications were promptly discontinued upon tertiary hospital admission.

Once the outside hospitals contacted the tertiary hospital for a referral, the mean length of time between the transfer request and Physician Access Line call was 17.13 minutes (Table 4). Following the transfer request, the mean length of time for arrival at the tertiary hospital was 6.22 hours. The mean length of stay at the outside hospital prior to the patient being transferred was 3.84 days.

Comment

This retrospective study examined 71 patients with biopsy-confirmed SJS, SJS/TEN overlap, or TEN to evaluate differences in clinical outcomes between direct and transfer admissions. Transfer patients had a higher mean maximum affected BSA (38.55% vs 19.14% [P=.005]) and elevated SCORTEN (1.92 vs 1.07 [P=.029]); a higher number of transfer patients were admitted to the ICU (19 vs 5 [P=.014]) and burn unit (9 vs 2 [P=.096]), and this group also demonstrated longer hospitalization stays (13.71 vs 7.17 [P<.0001]). There were more complications among transfer patients, including bacteremia (16 vs 4 [P=.025]), which is consistent with findings from the existing literature.³

Once the decision for transfer of the patients included in our study was initiated and accepted, there was a prompt response and transfer of care; the mean length of time for Physician Access Line request was 17.13 minutes, and the mean transfer time to arrive at the tertiary hospital was 6.22 hours; however, patients spent an average of 3.84 days at outside hospitals, reflecting that transfer calls frequently were initiated due to urgent clinical decline of the patient rather than as an early intervention strategy. The management at outside hospitals often included the continuation of antimicrobial medications, which were discontinued upon transfer to AHWFBMC. Causative agents were either previously prescribed for a new medical condition or initiated for the management of suspected infections at outside hospitals. This may reflect the difficulty in correctly diagnosing SJS/TEN and initiating appropriate management at hospital facilities without an inpatient dermatologist.

The presence of inpatient dermatologists can improve the diagnostic accuracy and treatment of various conditions.^4,5 Dermatology consultations added or changed 77% of treatment plans for 271 hospitalized patients.⁴ The impact of this intervention is reflected by the success of early dermatology consultations in reducing the length of hospitalization and use of inappropriate treatments in the care of skin diseases.^6-8

Access to dermatologic care has been an identified need in inpatient hospitals that may limit the ability of hospitals to promptly treat serious conditions such as SJS/TEN.⁹ From an inpatient dermatology study from 2013 through 2019, 98.2% of 782 inpatient dermatologists reside in metropolitan areas, limiting the availability of care for rural patients; this study also found a decreasing number of facilities with inpatient dermatologists.¹⁰

The limitations of our study include a small sample size of 71 patients, which restricted the generalizability of our results. Our study also was based at a single tertiary center, which thereby limited the findings to this geographic area. It also was difficult to match patients by their demographic and comorbid conditions. The retrospective study design depended on the accuracy and completeness of medical records, which can introduce information bias. Future studies should compare the clinical outcomes of SJS/TEN based on burn unit and ICU admissions.

Conclusion

Prompt identification of SJS/TEN and rapid transfer to hospitals with inpatient dermatology are essential to optimize patient outcomes. Developing and validating SJS/TEN diagnosis and transfer protocols across multiple institutions may be helpful.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening conditions that involve widespread necrosis of the skin and mucous membranes.¹ Guidelines for SJS and TEN recommend management in hospitals with access to inpatient dermatology to provide immediate interventions that are necessary for achieving optimal patient outcomes.² A delay in admission of 5 days or more after onset of symptoms has been associated with increases in overall mortality, bacteremia, intensive care unit (ICU) admission, and length of stay.³ Patients who are not directly admitted to specialized facilities and require transfer from other hospitals may experience delays in receiving critical interventions, further increasing the risk for mortality and complications. In this study, we analyzed the clinical outcomes of patients with SJS/TEN in relation to their admission pathway.

Methods

A single-center retrospective chart review was performed at Atrium Health Wake Forest Baptist Medical Center (AHWFBMC) in Winston-Salem, North Carolina. Participants were identified using i2b2, an informatics tool compliant with the Health Insurance Portability and Accountability Act for integrating biology and the bedside. Inclusion criteria were having a diagnosis of SJS (International Classification of Diseases, Tenth Revision, code L51.1; International Classification of Diseases, Ninth Revision, code 695.13), TEN (International Classification of Diseases, Tenth Revision, code L51.2; International Classification of Diseases, Ninth Revision, code 695.15) or Lyell syndrome from January 2012 to December 2024. Patients with erythema multiforme or bullous drug eruption were excluded, as these conditions initially were misdiagnosed as SJS or TEN. Patients with only a reported history of prior SJS or TEN also were excluded.

The following clinical outcomes were assessed: demographics, comorbidities, age at disease onset, outside hospital transfer status, complications during admission, inpatient length of stay in days, age of mortality (if applicable), culprit medications, interventions received, Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) upon admission, site of admission (eg, floor bed, ICU, medical ICU, burn unit), and length of disease process prior to hospital admission. Patients then were categorized as either direct or transfer admissions based on the initial point of care and admission process. Direct admissions included patients who presented to the AHWFBMC emergency department and were subsequently admitted. Transfer patients included patients who initially presented to an outside hospital and were transferred to AHWFBMC. Data regarding the wait time for Physician Access Line requests and the time elapsed from the initial transfer call to arrival at the tertiary hospital also were collected—this is a method that outside hospitals can use to contact physicians at the tertiary hospital for a possible transfer. Statistical analysis was performed using unpaired t tests and X² tests as necessary using GraphPad By Dotmatics Prism.

Results

A total of 112 patients were included in the analysis; of these, 71 had a diagnosis with biopsy confirmation of SJS, SJS/TEN overlap, or TEN (Table 1). Forty-one patients were excluded due to having a diagnosis of erythema multiforme or bullous drug eruption or a reported history of prior SJS or TEN without hospitalization. All biopsies were performed at AHWFBMC. Of the 71 confirmed patients with SJS/TEN, 54 (76%) were female with a mean age of 44 years. The majority of patients identified as Black (35 [49%]) or White (27 [38%]), along with Asian (7 [10%]) and other (2 [3%]). The most common comorbidity was cardiovascular disease in 42 (59%) patients, followed by type 2 diabetes in 36 (51%) patients. Among these 71 patients with SJS/TEN, 29 (41%) were directly admitted to the tertiary hospital, while 42 (59%) were transferred from outside hospitals.

Of the 71 confirmed patients with SJS/TEN, sulfonamides were identified as the most common inciting drug in 25 (41%) patients, followed by beta-lactam antibiotics in 16 (23%) patients (Table 2). This is consistent with previous literature of sulfamethoxazole with trimethoprim as the primary causative drug for SJS and TEN in the United States.¹

Clinical Outcomes—Of the 71 patients, there were 23 (32%) cases of SJS, 29 (41%) cases of SJS/TEN overlap, and 19 (27%) cases of TEN (eTable). The initial and maximum affected body surface area (BSA) was higher in transfer admissions, with a mean maximum BSA of 38.55% in the transfer group compared to 19.14% in the direct admissions. The mean SCORTEN (range, 0-5) was 1.6 overall, with a higher mean score of 1.92 in the transfer group compared to 1.07 in the direct admissions.

Transfer patients had a longer mean stay at the tertiary hospital (13.71 d) compared to direct admissions (7.17 d). The mean time from symptom onset until tertiary hospital admission was 8.5 days; transfer and direct admission patients had similar mean time from symptom onset of 9.02 days and 7.86 days, respectively. Although the duration of cutaneous symptoms from onset until tertiary hospital admission was similar (P=.283) between direct admissions (7.86 d) and transfer patients (9.02 d), the transfer group presented with greater disease severity at the time of admission. Transfer patients had a higher mean maximum BSA involvement (38.55% vs 19.14% [P=.005]), elevated SCORTEN (1.92 vs 1.07 [P=.029]), and longer mean hospital stays (13.71 d vs 7.17 d [P<.0001]) compared to direct admissions.

Despite the absence of mortality in both groups, transfer patients showed a higher number of ICU admissions (19 vs 5 [P=.014]) and burn unit admissions (9 vs 2 [P=.096]), bacteremia (16 vs 4 [P=.025]), acute kidney injury (13 vs 10 [P=.755]), acute respiratory failure (12 vs 5 [P=.272]), and transaminitis (8 vs 3 [P=.319]).

Outside Hospital Treatments—All outside hospitals provided supportive care with intravenous fluids and acetaminophen; however, further care provided at outside hospitals varied (Table 3), with transfer patients most frequently being treated with diphenhydramine (69% [29/42]), antimicrobial medications (57% [24/42]), steroids (40%), and epinephrine (10% [4/42]). Some patients may have received more than one of these treatments. Based on outside hospital treatments, the primary care teams’ main clinical concerns were allergic reactions and infection, as 33 (79%) patients received diphenhydramine (29 [89%]) or epinephrine (4 [12%]) and 24 (52%) received antimicrobial medications. Of the 42 transfer patients, 24 (57%) received or continued these medications before transfer; the medications were promptly discontinued upon tertiary hospital admission.

Once the outside hospitals contacted the tertiary hospital for a referral, the mean length of time between the transfer request and Physician Access Line call was 17.13 minutes (Table 4). Following the transfer request, the mean length of time for arrival at the tertiary hospital was 6.22 hours. The mean length of stay at the outside hospital prior to the patient being transferred was 3.84 days.

Comment

This retrospective study examined 71 patients with biopsy-confirmed SJS, SJS/TEN overlap, or TEN to evaluate differences in clinical outcomes between direct and transfer admissions. Transfer patients had a higher mean maximum affected BSA (38.55% vs 19.14% [P=.005]) and elevated SCORTEN (1.92 vs 1.07 [P=.029]); a higher number of transfer patients were admitted to the ICU (19 vs 5 [P=.014]) and burn unit (9 vs 2 [P=.096]), and this group also demonstrated longer hospitalization stays (13.71 vs 7.17 [P<.0001]). There were more complications among transfer patients, including bacteremia (16 vs 4 [P=.025]), which is consistent with findings from the existing literature.³

Once the decision for transfer of the patients included in our study was initiated and accepted, there was a prompt response and transfer of care; the mean length of time for Physician Access Line request was 17.13 minutes, and the mean transfer time to arrive at the tertiary hospital was 6.22 hours; however, patients spent an average of 3.84 days at outside hospitals, reflecting that transfer calls frequently were initiated due to urgent clinical decline of the patient rather than as an early intervention strategy. The management at outside hospitals often included the continuation of antimicrobial medications, which were discontinued upon transfer to AHWFBMC. Causative agents were either previously prescribed for a new medical condition or initiated for the management of suspected infections at outside hospitals. This may reflect the difficulty in correctly diagnosing SJS/TEN and initiating appropriate management at hospital facilities without an inpatient dermatologist.

The presence of inpatient dermatologists can improve the diagnostic accuracy and treatment of various conditions.^4,5 Dermatology consultations added or changed 77% of treatment plans for 271 hospitalized patients.⁴ The impact of this intervention is reflected by the success of early dermatology consultations in reducing the length of hospitalization and use of inappropriate treatments in the care of skin diseases.^6-8

Access to dermatologic care has been an identified need in inpatient hospitals that may limit the ability of hospitals to promptly treat serious conditions such as SJS/TEN.⁹ From an inpatient dermatology study from 2013 through 2019, 98.2% of 782 inpatient dermatologists reside in metropolitan areas, limiting the availability of care for rural patients; this study also found a decreasing number of facilities with inpatient dermatologists.¹⁰

The limitations of our study include a small sample size of 71 patients, which restricted the generalizability of our results. Our study also was based at a single tertiary center, which thereby limited the findings to this geographic area. It also was difficult to match patients by their demographic and comorbid conditions. The retrospective study design depended on the accuracy and completeness of medical records, which can introduce information bias. Future studies should compare the clinical outcomes of SJS/TEN based on burn unit and ICU admissions.

Conclusion

Prompt identification of SJS/TEN and rapid transfer to hospitals with inpatient dermatology are essential to optimize patient outcomes. Developing and validating SJS/TEN diagnosis and transfer protocols across multiple institutions may be helpful.

THE COMPARISON:

• A. Erythematotelangiectatic rosacea in a polygonal vascular pattern on the cheeks in a Black woman who also has eyelid hypopigmentation due to vitiligo.
• B. Rhinophymatous rosacea in a Hispanic woman who also has papules and pustules on the chin and upper lip region as well as facial scarring from severe inflammatory acne during her teen years.
• C. Papulopustular rosacea in a Hispanic man.

Rosacea is a chronic inflammatory condition characterized by facial flushing and persistent erythema of the central face, typically affecting the cheeks and nose. It also may manifest with papules, pustules, and telangiectasias. The 4 main subtypes of rosacea are erythematotelangiectatic, papulopustular, phymatous (involving thickening of the skin, often of the nose), and ocular (dry, itchy, or irritated eyes).¹ Patients also may report stinging, burning, dryness, and edema.² The etiology of rosacea is unclear but is believed to involve immune dysfunction, neurovascular dysregulation, certain microorganisms, and genetic predisposition.^1,2

Epidemiology

Rosacea often is associated with fair skin and more frequently is reported in individuals of Northern European descent.^1,2 While it may be less common in darker skin types, rosacea is not rare in patients with skin of color (SOC). A review of US outpatient data from 1993 to 2010 found that 2% of patients with rosacea were Black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino.³ Global estimates suggest that up to 40 million individuals with SOC may be affected by rosacea,⁴ with the reported prevalence as high as 10%.² Although early research linked rosacea primarily to adults older than 30 years, newer data show peak prevalence between ages 25 to 39 years, suggesting that younger adults may be affected more than previously recognized.⁵

Key Clinical Features

In addition to the traditional subtypes, updated guidelines recommend a phenotype- based approach to diagnosing rosacea focusing on observable features such as persistent redness in the central face and thickened skin rather than classifying patients into broad categories. A diagnosis can be made when at least one diagnostic feature is present (eg, fixed facial erythema or phymatous changes) or when 2 or more major features are observed (eg, papules, pustules, flushing, visible blood vessels, or ocular findings).⁶

In individuals with darker skin types, erythema may not be bright red; rather, the skin may appear pink, reddish-brown, violaceous, or dusky brown.⁷ Postinflammatory hyperpigmentation, which is common in darker skin tones, can further mask erythema.² Pressing a microscope slide or magnifying glass against the skin can help assess for blanching, which is indicative of erythema. Telangiectasias also may be more challenging to appreciate in patients with SOC and typically require bright, shadow-free lighting or dermoscopy for detection.²

Skin thickening across the cheeks and nose with overlying acneform papules can be diagnostic clues of rosacea in darker skin types and help distinguish it from acne.² It also is important to distinguish rosacea from systemic lupus erythematosus, which typically manifests as a malar rash that spares the nasolabial folds and is nonpustular. If uncertain, consider serologic testing for antinuclear antibodies, patch testing, or biopsy.⁸

Worth Noting

Treatment of rosacea is focused on managing symptoms and reducing flares. First-line strategies include behavioral modifications and trigger avoidance, such as minimizing sun exposure and avoiding consumption of alcohol and spicy foods.⁹ Gentle skin care practices are essential, including the use of light, fragrance-free, nonirritating cleansers and moisturizers at least once daily. Application of sunscreen with an SPF of at least 30 also is routinely recommended.^9,10 Additionally, patients should be counseled to avoid harsh cleansers, such as exfoliants, astringents, and chemicals that may further diminish the skin barrier.¹⁰

Treatment options approved by the US Food and Drug Administration for rosacea include oral doxycycline, oral minocycline, topical brimonidine, oxymetazoline, ivermectin, metronidazole, azelaic acid, sodium sulfacetamide/sulfur, encapsulated benzoyl peroxide cream, and minocycline.^11-13

Topical treatment options commonly used off-label for rosacea include topical clindamycin, topical retinoids, and azithromycin. Oral tetracyclines should be avoided in children and pregnant women; instead, oral erythromycin and topical metronidazole commonly are used.¹⁴

Laser or intense pulsed light therapy may be considered, although results have been mixed, and the long-term benefits are uncertain. Given the higher risk for postinflammatory hyperpigmentation in patients with SOC, these modalities should be used cautiously.¹⁵ Among the available options, the Nd:YAG laser is preferred in darker skin types due to its safety profile.¹⁶ A small case series reported successful CO2 laser treatment for rhinophyma in patients with melanated skin; however, some patients developed localized scarring, suggesting that conservative depth settings should be used to reduce risk for this adverse event.¹⁷

Health Disparity Highlight

Rosacea may be underdiagnosed in individuals with darker skin types,^2,15,18 likely due in part to reduced contrast between erythema and background skin tone, which can make features such as flushing and telangiectasias harder to appreciate.^1,10,15

Although tools to assess erythema exist, they rarely are used in everyday clinical practice.¹⁰ In patients with deeply pigmented skin, ensuring adequate examination room lighting and using dermoscopy can help identify any subtle vascular or textural changes localized across the central face. While various imaging techniques are used in clinical trials to monitor treatment response, few have been studied and optimized across a wide range of skin tones.¹⁰ There is a need for dermatologic assessment tools that better capture the degree of erythema, inflammation, and vascular features of rosacea in pigmented skin. Emerging research is focused on developing more equitable imaging technologies.¹⁹

THE COMPARISON:

• A. Erythematotelangiectatic rosacea in a polygonal vascular pattern on the cheeks in a Black woman who also has eyelid hypopigmentation due to vitiligo.
• B. Rhinophymatous rosacea in a Hispanic woman who also has papules and pustules on the chin and upper lip region as well as facial scarring from severe inflammatory acne during her teen years.
• C. Papulopustular rosacea in a Hispanic man.

Rosacea is a chronic inflammatory condition characterized by facial flushing and persistent erythema of the central face, typically affecting the cheeks and nose. It also may manifest with papules, pustules, and telangiectasias. The 4 main subtypes of rosacea are erythematotelangiectatic, papulopustular, phymatous (involving thickening of the skin, often of the nose), and ocular (dry, itchy, or irritated eyes).¹ Patients also may report stinging, burning, dryness, and edema.² The etiology of rosacea is unclear but is believed to involve immune dysfunction, neurovascular dysregulation, certain microorganisms, and genetic predisposition.^1,2

Epidemiology

Rosacea often is associated with fair skin and more frequently is reported in individuals of Northern European descent.^1,2 While it may be less common in darker skin types, rosacea is not rare in patients with skin of color (SOC). A review of US outpatient data from 1993 to 2010 found that 2% of patients with rosacea were Black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino.³ Global estimates suggest that up to 40 million individuals with SOC may be affected by rosacea,⁴ with the reported prevalence as high as 10%.² Although early research linked rosacea primarily to adults older than 30 years, newer data show peak prevalence between ages 25 to 39 years, suggesting that younger adults may be affected more than previously recognized.⁵

Key Clinical Features

In addition to the traditional subtypes, updated guidelines recommend a phenotype- based approach to diagnosing rosacea focusing on observable features such as persistent redness in the central face and thickened skin rather than classifying patients into broad categories. A diagnosis can be made when at least one diagnostic feature is present (eg, fixed facial erythema or phymatous changes) or when 2 or more major features are observed (eg, papules, pustules, flushing, visible blood vessels, or ocular findings).⁶

In individuals with darker skin types, erythema may not be bright red; rather, the skin may appear pink, reddish-brown, violaceous, or dusky brown.⁷ Postinflammatory hyperpigmentation, which is common in darker skin tones, can further mask erythema.² Pressing a microscope slide or magnifying glass against the skin can help assess for blanching, which is indicative of erythema. Telangiectasias also may be more challenging to appreciate in patients with SOC and typically require bright, shadow-free lighting or dermoscopy for detection.²

Skin thickening across the cheeks and nose with overlying acneform papules can be diagnostic clues of rosacea in darker skin types and help distinguish it from acne.² It also is important to distinguish rosacea from systemic lupus erythematosus, which typically manifests as a malar rash that spares the nasolabial folds and is nonpustular. If uncertain, consider serologic testing for antinuclear antibodies, patch testing, or biopsy.⁸

Worth Noting

Treatment of rosacea is focused on managing symptoms and reducing flares. First-line strategies include behavioral modifications and trigger avoidance, such as minimizing sun exposure and avoiding consumption of alcohol and spicy foods.⁹ Gentle skin care practices are essential, including the use of light, fragrance-free, nonirritating cleansers and moisturizers at least once daily. Application of sunscreen with an SPF of at least 30 also is routinely recommended.^9,10 Additionally, patients should be counseled to avoid harsh cleansers, such as exfoliants, astringents, and chemicals that may further diminish the skin barrier.¹⁰

Treatment options approved by the US Food and Drug Administration for rosacea include oral doxycycline, oral minocycline, topical brimonidine, oxymetazoline, ivermectin, metronidazole, azelaic acid, sodium sulfacetamide/sulfur, encapsulated benzoyl peroxide cream, and minocycline.^11-13

Topical treatment options commonly used off-label for rosacea include topical clindamycin, topical retinoids, and azithromycin. Oral tetracyclines should be avoided in children and pregnant women; instead, oral erythromycin and topical metronidazole commonly are used.¹⁴

Laser or intense pulsed light therapy may be considered, although results have been mixed, and the long-term benefits are uncertain. Given the higher risk for postinflammatory hyperpigmentation in patients with SOC, these modalities should be used cautiously.¹⁵ Among the available options, the Nd:YAG laser is preferred in darker skin types due to its safety profile.¹⁶ A small case series reported successful CO2 laser treatment for rhinophyma in patients with melanated skin; however, some patients developed localized scarring, suggesting that conservative depth settings should be used to reduce risk for this adverse event.¹⁷

Health Disparity Highlight

Rosacea may be underdiagnosed in individuals with darker skin types,^2,15,18 likely due in part to reduced contrast between erythema and background skin tone, which can make features such as flushing and telangiectasias harder to appreciate.^1,10,15

Although tools to assess erythema exist, they rarely are used in everyday clinical practice.¹⁰ In patients with deeply pigmented skin, ensuring adequate examination room lighting and using dermoscopy can help identify any subtle vascular or textural changes localized across the central face. While various imaging techniques are used in clinical trials to monitor treatment response, few have been studied and optimized across a wide range of skin tones.¹⁰ There is a need for dermatologic assessment tools that better capture the degree of erythema, inflammation, and vascular features of rosacea in pigmented skin. Emerging research is focused on developing more equitable imaging technologies.¹⁹

THE COMPARISON:

• A. Erythematotelangiectatic rosacea in a polygonal vascular pattern on the cheeks in a Black woman who also has eyelid hypopigmentation due to vitiligo.
• B. Rhinophymatous rosacea in a Hispanic woman who also has papules and pustules on the chin and upper lip region as well as facial scarring from severe inflammatory acne during her teen years.
• C. Papulopustular rosacea in a Hispanic man.

Rosacea is a chronic inflammatory condition characterized by facial flushing and persistent erythema of the central face, typically affecting the cheeks and nose. It also may manifest with papules, pustules, and telangiectasias. The 4 main subtypes of rosacea are erythematotelangiectatic, papulopustular, phymatous (involving thickening of the skin, often of the nose), and ocular (dry, itchy, or irritated eyes).¹ Patients also may report stinging, burning, dryness, and edema.² The etiology of rosacea is unclear but is believed to involve immune dysfunction, neurovascular dysregulation, certain microorganisms, and genetic predisposition.^1,2

Epidemiology

Rosacea often is associated with fair skin and more frequently is reported in individuals of Northern European descent.^1,2 While it may be less common in darker skin types, rosacea is not rare in patients with skin of color (SOC). A review of US outpatient data from 1993 to 2010 found that 2% of patients with rosacea were Black, 2.3% were Asian or Pacific Islander, and 3.9% were Hispanic or Latino.³ Global estimates suggest that up to 40 million individuals with SOC may be affected by rosacea,⁴ with the reported prevalence as high as 10%.² Although early research linked rosacea primarily to adults older than 30 years, newer data show peak prevalence between ages 25 to 39 years, suggesting that younger adults may be affected more than previously recognized.⁵

Key Clinical Features

In addition to the traditional subtypes, updated guidelines recommend a phenotype- based approach to diagnosing rosacea focusing on observable features such as persistent redness in the central face and thickened skin rather than classifying patients into broad categories. A diagnosis can be made when at least one diagnostic feature is present (eg, fixed facial erythema or phymatous changes) or when 2 or more major features are observed (eg, papules, pustules, flushing, visible blood vessels, or ocular findings).⁶

In individuals with darker skin types, erythema may not be bright red; rather, the skin may appear pink, reddish-brown, violaceous, or dusky brown.⁷ Postinflammatory hyperpigmentation, which is common in darker skin tones, can further mask erythema.² Pressing a microscope slide or magnifying glass against the skin can help assess for blanching, which is indicative of erythema. Telangiectasias also may be more challenging to appreciate in patients with SOC and typically require bright, shadow-free lighting or dermoscopy for detection.²

Skin thickening across the cheeks and nose with overlying acneform papules can be diagnostic clues of rosacea in darker skin types and help distinguish it from acne.² It also is important to distinguish rosacea from systemic lupus erythematosus, which typically manifests as a malar rash that spares the nasolabial folds and is nonpustular. If uncertain, consider serologic testing for antinuclear antibodies, patch testing, or biopsy.⁸

Worth Noting

Treatment of rosacea is focused on managing symptoms and reducing flares. First-line strategies include behavioral modifications and trigger avoidance, such as minimizing sun exposure and avoiding consumption of alcohol and spicy foods.⁹ Gentle skin care practices are essential, including the use of light, fragrance-free, nonirritating cleansers and moisturizers at least once daily. Application of sunscreen with an SPF of at least 30 also is routinely recommended.^9,10 Additionally, patients should be counseled to avoid harsh cleansers, such as exfoliants, astringents, and chemicals that may further diminish the skin barrier.¹⁰

Treatment options approved by the US Food and Drug Administration for rosacea include oral doxycycline, oral minocycline, topical brimonidine, oxymetazoline, ivermectin, metronidazole, azelaic acid, sodium sulfacetamide/sulfur, encapsulated benzoyl peroxide cream, and minocycline.^11-13

Topical treatment options commonly used off-label for rosacea include topical clindamycin, topical retinoids, and azithromycin. Oral tetracyclines should be avoided in children and pregnant women; instead, oral erythromycin and topical metronidazole commonly are used.¹⁴

Laser or intense pulsed light therapy may be considered, although results have been mixed, and the long-term benefits are uncertain. Given the higher risk for postinflammatory hyperpigmentation in patients with SOC, these modalities should be used cautiously.¹⁵ Among the available options, the Nd:YAG laser is preferred in darker skin types due to its safety profile.¹⁶ A small case series reported successful CO2 laser treatment for rhinophyma in patients with melanated skin; however, some patients developed localized scarring, suggesting that conservative depth settings should be used to reduce risk for this adverse event.¹⁷

Health Disparity Highlight

Rosacea may be underdiagnosed in individuals with darker skin types,^2,15,18 likely due in part to reduced contrast between erythema and background skin tone, which can make features such as flushing and telangiectasias harder to appreciate.^1,10,15

Although tools to assess erythema exist, they rarely are used in everyday clinical practice.¹⁰ In patients with deeply pigmented skin, ensuring adequate examination room lighting and using dermoscopy can help identify any subtle vascular or textural changes localized across the central face. While various imaging techniques are used in clinical trials to monitor treatment response, few have been studied and optimized across a wide range of skin tones.¹⁰ There is a need for dermatologic assessment tools that better capture the degree of erythema, inflammation, and vascular features of rosacea in pigmented skin. Emerging research is focused on developing more equitable imaging technologies.¹⁹

THE DIAGNOSIS: Atypical Fibroxanthoma

Given the appearance of the nodule and the absence of features of a keloid scar, a soft-tissue or adnexal tumor was suspected. Histology revealed a thin epidermis with loss of rete ridges and a Grenz zone. There was a nodular uncircumscribed dermal proliferation of spindle cells forming interweaving fascicles with elongated ovoid nuclei and prominent nucleoli (Figure). There was moderate cellular and nuclear atypia, and no necrosis was observed. The spindle cells stained positive for CD10 and negative for AE1/AE3, cytokeratin 5/6, S100, melanoma triple marker, Factor XIII 1, ERG, CD31, CD34, desmin, and smooth muscle actin; ERG, CD31, CD34, and SMA highlighted small vessels within the tumor. The histologic diagnosis was an atypical spindle cell tumor favoring atypical fibroxanthoma (AFX). The excisional biopsy margins were clear.

The patient was referred to surgical oncology to consider re-excision of margins after the diagnosis was made. A chest radiograph was clear, and magnetic resonance imaging showed mild skin thickening and image enhancement at the left shoulder—possibly a postsurgical change—with no nodularity suggesting a residual or recurrent tumor. Surgical oncology determined that the patient did not require further excision and placed him on regular follow-up every 2 to 3 months for the next 2 years.

uncertain origin that is considered to be on a spectrum with the more aggressive pleomorphic dermal sarcoma (PDS); it can be distinguished from PDS by histologic features such as nerve or vessel invasion.¹ Both entities share oncogenes (eg, tumor protein 53 gene mutations) and are histologically and immunohistochemically similar. Atypical fibroxanthoma largely is viewed as an intermediate-risk tumor that is locally aggressive but rarely metastasizes, with a reported local recurrence rate of 5% to 11% and metastasis risk of 1% to 2%. Conversely, PDS is a more aggressive diagnosis with a high risk for local recurrence and metastasis (7%-69% and 4%-20%, respectively).¹

Atypical fibroxanthomas may mimic other entities, both clinically and histologically. It commonly manifests as a flesh-colored to erythematous, sometimes ulcerated nodule on sun-exposed skin in elderly patients, leading to a broad range of clinical differential diagnoses, including other primary cutaneous malignancies (eg, squamous cell carcinoma, amelanotic melanoma), cutaneous sarcomas (eg, dermatofibrosarcoma protuberans), adnexal and other tumors (eg, pleomorphic fibroma, pilomatricoma), cutaneous metastases, and even keloid scars. As the differentials can look clinically similar, a skin biopsy may be necessary to confirm the diagnosis.

Histologically, AFX tends to show an undifferentiated pleomorphic spindle cell morphology. Notably, histology can be highly variable, with other reported histologic patterns including keloidlike, pleomorphic, epithelioid, rhabdoid, clear-cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, and osteoclast-rich patterns.² Thus, the histologic differential diagnosis also is broad, and AFX primarily is a diagnosis of exclusion without specific immunohistochemical markers that serve to exclude other diagnoses. For example, AFX tends to stain positive for CD10 and CD68, though these are not specific markers for AFX. Furthermore, although certain histologic markers may commonly be more positive in AFX than PDS (eg, CD74 stains positive in 20% of AFXs and only 1% of PDSs), this is not reliable enough to be diagnostic.³ As such, AFX is distinguished from PDS primarily by histologic features such as subcutaneous tissue invasion, vascular or perineural invasion, necrosis, or local invasion/ metastases.¹ Given the rarity of both tumors, no established management guidelines exist, although excision (wide local excision or Mohs micrographic surgery) usually is recommended, with some authors suggesting margins of 1 cm for AFX and 2 cm to 3 cm for PDS.¹

This atypical case of AFX arising in non–sun-exposed skin in a young man raises questions about whether unknown genetic factors or possibly prior immunosuppression could have contributed to the development of the tumor. A thorough history and physical examination can provide valuable clues for biopsy, including ongoing growth, absence of known prior trauma or acne at the site, and clinical appearance, such as the reddish, solitary, dome-shaped lesion in our patient.

THE DIAGNOSIS: Atypical Fibroxanthoma

Given the appearance of the nodule and the absence of features of a keloid scar, a soft-tissue or adnexal tumor was suspected. Histology revealed a thin epidermis with loss of rete ridges and a Grenz zone. There was a nodular uncircumscribed dermal proliferation of spindle cells forming interweaving fascicles with elongated ovoid nuclei and prominent nucleoli (Figure). There was moderate cellular and nuclear atypia, and no necrosis was observed. The spindle cells stained positive for CD10 and negative for AE1/AE3, cytokeratin 5/6, S100, melanoma triple marker, Factor XIII 1, ERG, CD31, CD34, desmin, and smooth muscle actin; ERG, CD31, CD34, and SMA highlighted small vessels within the tumor. The histologic diagnosis was an atypical spindle cell tumor favoring atypical fibroxanthoma (AFX). The excisional biopsy margins were clear.

The patient was referred to surgical oncology to consider re-excision of margins after the diagnosis was made. A chest radiograph was clear, and magnetic resonance imaging showed mild skin thickening and image enhancement at the left shoulder—possibly a postsurgical change—with no nodularity suggesting a residual or recurrent tumor. Surgical oncology determined that the patient did not require further excision and placed him on regular follow-up every 2 to 3 months for the next 2 years.

uncertain origin that is considered to be on a spectrum with the more aggressive pleomorphic dermal sarcoma (PDS); it can be distinguished from PDS by histologic features such as nerve or vessel invasion.¹ Both entities share oncogenes (eg, tumor protein 53 gene mutations) and are histologically and immunohistochemically similar. Atypical fibroxanthoma largely is viewed as an intermediate-risk tumor that is locally aggressive but rarely metastasizes, with a reported local recurrence rate of 5% to 11% and metastasis risk of 1% to 2%. Conversely, PDS is a more aggressive diagnosis with a high risk for local recurrence and metastasis (7%-69% and 4%-20%, respectively).¹

Atypical fibroxanthomas may mimic other entities, both clinically and histologically. It commonly manifests as a flesh-colored to erythematous, sometimes ulcerated nodule on sun-exposed skin in elderly patients, leading to a broad range of clinical differential diagnoses, including other primary cutaneous malignancies (eg, squamous cell carcinoma, amelanotic melanoma), cutaneous sarcomas (eg, dermatofibrosarcoma protuberans), adnexal and other tumors (eg, pleomorphic fibroma, pilomatricoma), cutaneous metastases, and even keloid scars. As the differentials can look clinically similar, a skin biopsy may be necessary to confirm the diagnosis.

Histologically, AFX tends to show an undifferentiated pleomorphic spindle cell morphology. Notably, histology can be highly variable, with other reported histologic patterns including keloidlike, pleomorphic, epithelioid, rhabdoid, clear-cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, and osteoclast-rich patterns.² Thus, the histologic differential diagnosis also is broad, and AFX primarily is a diagnosis of exclusion without specific immunohistochemical markers that serve to exclude other diagnoses. For example, AFX tends to stain positive for CD10 and CD68, though these are not specific markers for AFX. Furthermore, although certain histologic markers may commonly be more positive in AFX than PDS (eg, CD74 stains positive in 20% of AFXs and only 1% of PDSs), this is not reliable enough to be diagnostic.³ As such, AFX is distinguished from PDS primarily by histologic features such as subcutaneous tissue invasion, vascular or perineural invasion, necrosis, or local invasion/ metastases.¹ Given the rarity of both tumors, no established management guidelines exist, although excision (wide local excision or Mohs micrographic surgery) usually is recommended, with some authors suggesting margins of 1 cm for AFX and 2 cm to 3 cm for PDS.¹

This atypical case of AFX arising in non–sun-exposed skin in a young man raises questions about whether unknown genetic factors or possibly prior immunosuppression could have contributed to the development of the tumor. A thorough history and physical examination can provide valuable clues for biopsy, including ongoing growth, absence of known prior trauma or acne at the site, and clinical appearance, such as the reddish, solitary, dome-shaped lesion in our patient.

THE DIAGNOSIS: Atypical Fibroxanthoma

Given the appearance of the nodule and the absence of features of a keloid scar, a soft-tissue or adnexal tumor was suspected. Histology revealed a thin epidermis with loss of rete ridges and a Grenz zone. There was a nodular uncircumscribed dermal proliferation of spindle cells forming interweaving fascicles with elongated ovoid nuclei and prominent nucleoli (Figure). There was moderate cellular and nuclear atypia, and no necrosis was observed. The spindle cells stained positive for CD10 and negative for AE1/AE3, cytokeratin 5/6, S100, melanoma triple marker, Factor XIII 1, ERG, CD31, CD34, desmin, and smooth muscle actin; ERG, CD31, CD34, and SMA highlighted small vessels within the tumor. The histologic diagnosis was an atypical spindle cell tumor favoring atypical fibroxanthoma (AFX). The excisional biopsy margins were clear.

The patient was referred to surgical oncology to consider re-excision of margins after the diagnosis was made. A chest radiograph was clear, and magnetic resonance imaging showed mild skin thickening and image enhancement at the left shoulder—possibly a postsurgical change—with no nodularity suggesting a residual or recurrent tumor. Surgical oncology determined that the patient did not require further excision and placed him on regular follow-up every 2 to 3 months for the next 2 years.

uncertain origin that is considered to be on a spectrum with the more aggressive pleomorphic dermal sarcoma (PDS); it can be distinguished from PDS by histologic features such as nerve or vessel invasion.¹ Both entities share oncogenes (eg, tumor protein 53 gene mutations) and are histologically and immunohistochemically similar. Atypical fibroxanthoma largely is viewed as an intermediate-risk tumor that is locally aggressive but rarely metastasizes, with a reported local recurrence rate of 5% to 11% and metastasis risk of 1% to 2%. Conversely, PDS is a more aggressive diagnosis with a high risk for local recurrence and metastasis (7%-69% and 4%-20%, respectively).¹

Atypical fibroxanthomas may mimic other entities, both clinically and histologically. It commonly manifests as a flesh-colored to erythematous, sometimes ulcerated nodule on sun-exposed skin in elderly patients, leading to a broad range of clinical differential diagnoses, including other primary cutaneous malignancies (eg, squamous cell carcinoma, amelanotic melanoma), cutaneous sarcomas (eg, dermatofibrosarcoma protuberans), adnexal and other tumors (eg, pleomorphic fibroma, pilomatricoma), cutaneous metastases, and even keloid scars. As the differentials can look clinically similar, a skin biopsy may be necessary to confirm the diagnosis.

Histologically, AFX tends to show an undifferentiated pleomorphic spindle cell morphology. Notably, histology can be highly variable, with other reported histologic patterns including keloidlike, pleomorphic, epithelioid, rhabdoid, clear-cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, and osteoclast-rich patterns.² Thus, the histologic differential diagnosis also is broad, and AFX primarily is a diagnosis of exclusion without specific immunohistochemical markers that serve to exclude other diagnoses. For example, AFX tends to stain positive for CD10 and CD68, though these are not specific markers for AFX. Furthermore, although certain histologic markers may commonly be more positive in AFX than PDS (eg, CD74 stains positive in 20% of AFXs and only 1% of PDSs), this is not reliable enough to be diagnostic.³ As such, AFX is distinguished from PDS primarily by histologic features such as subcutaneous tissue invasion, vascular or perineural invasion, necrosis, or local invasion/ metastases.¹ Given the rarity of both tumors, no established management guidelines exist, although excision (wide local excision or Mohs micrographic surgery) usually is recommended, with some authors suggesting margins of 1 cm for AFX and 2 cm to 3 cm for PDS.¹

This atypical case of AFX arising in non–sun-exposed skin in a young man raises questions about whether unknown genetic factors or possibly prior immunosuppression could have contributed to the development of the tumor. A thorough history and physical examination can provide valuable clues for biopsy, including ongoing growth, absence of known prior trauma or acne at the site, and clinical appearance, such as the reddish, solitary, dome-shaped lesion in our patient.

To the Editor:

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is characterized by age-related morphology and distribution of lesions. Although AD can manifest at any age, it often develops during childhood, with an estimated worldwide prevalence of 15% to 25% in children and 1% to 10% in adults.¹ Clinical manifestation includes chronic or recurrent xerosis, pruritic eczematous lesions involving the flexural and extensor areas, and cutaneous infections. Immediate skin test reactivity and elevated total IgE levels can be found in up to 80% of patients.²

Although the pathogenesis of AD is complex, multifactorial, and not completely understood, some studies have highlighted the central role of a type 2 immune response, resulting in skin barrier dysfunction, cutaneous inflammation, and neuroimmune dysregulation.^3,4 The primary goals of treatment are to mitigate these factors through improvement of symptoms and long-term disease control. Topical emollients are used to repair the epidermal barrier, and topical anti-inflammatory therapy with corticosteroids or calcineurin inhibitors might be applied during flares; however, systemic treatment is essential for patients with moderate to severe AD that is not controlled with topical treatment or phototherapy.⁵

Until recently, systemic immunosuppressant agents such as corticosteroids, cyclosporine, and methotrexate were the only systemic treatment options for severe AD; however, their effectiveness is limited and they may cause serious long-term adverse events, limiting their regular usage, especially in children.⁶

Therapies that target type 2 immune responses include anti–IL-4/IL-13, anti–IL-13, and anti–IL-31 biologics. Dupilumab is a fully human monoclonal antibody targeting the type 2 immune response. This biologic directly binds to IL-4Rα,which prevents signaling by both the IL-4 and IL-13 pathways. Dupilumab was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD, with demonstrated efficacy and a favorable safety profile.⁵

In addition to biologics, Janus kinase (JAK) inhibitors belong to the small-molecule class. These drugs block the JAK/STAT intracellular signaling pathway, leading to inhibition of downstream effects triggered by several cytokines related to AD pathogenesis. Upadacitinib is an oral JAK inhibitor that was approved by the FDA in 2022 for treatment of severe AD in adults and children aged 12 years and older. This drug promotes a selective and reversible JAK-1 inhibition and has demonstrated rapid onset of action and a sustained reduction in the signs and symptoms of AD.⁷ We report the case of a child with recalcitrant severe AD that showed significant clinical improvement following off-label treatment with upadacitinib after showing a poor clinical response to dupilumab.

A 9-year-old girl presented to our pediatrics department with progressive worsening of severe AD over the previous 2 years. The patient had been diagnosed with AD at 6 months old, at which time she was treated with several prescribed moisturizers, topical and systemic corticosteroids, and calcineurin inhibitors with no clinical improvement.

The patient initially presented to us for evaluation of severe pruritus and associated sleep loss at age 7 years; physical examination revealed severe xerosis and disseminated pruritic eczematous lesions. Her SCORAD (SCORing Atopic Dermatitis) score was 70 (range, 0-103), and laboratory testing showed a high eosinophil count (1.5×10³/μL [range, 0-0.6×10³], 13%) and IgE level (1686 κU/L [range, 0-90]); a skin prick test on the forearm was positive for Blomia tropicalis.

Following her presentation with severe AD at 7 years old, the patient was prescribed systemic treatments including methotrexate and cyclosporine. During treatment with these agents, she presented to our department with several bacterial skin infections that required oral and intravenous antibiotics for treatment. These agents ultimately were discontinued after 12 months due to the adverse effects and poor clinical improvement. At age 8 years, the patient received an initial 600-mg dose of dupilumab followed by 300 mg subcutaneously every 4 weeks for 6 months along with topical corticosteroids and emollients. During treatment with dupilumab, the patient showed no clinical improvement (SCORAD score, 62). Therefore, we decided to change the dose to 200 mg every 2 weeks. The patient still showed no improvement and presented at age 9 years with moderate conjunctivitis and oculocutaneous infection caused by herpes simplex virus, which required treatment with oral acyclovir (Figure 1).

Considering the severe and refractory clinical course and the poor response to the recommended treatments for the patient’s age, oral upadacitinib was administered off label at a dose of 15 mg once daily after informed consent was obtained from her parents. She returned for follow-up once weekly for 1 month. Three days after starting treatment with upadacitinib, she showed considerable improvement in itch, and her SCORAD score decreased from 62 to 31 after 15 days. After 2 months of treatment, she reported no pruritus or sleep loss, and her SCORAD score was 4.5 (Figure 2). The results of a complete blood count, coagulation function test, and liver and kidney function tests were normal at 6-month and 12-month follow-up during upadacitinib therapy. No adverse effects were observed. The patient currently has completed 18 months of treatment, and the disease remains in complete remission.

Atopic dermatitis is highly prevalent in children. According to the International Study of Asthma and Allergies in Childhood, the prevalence of eczema in 2009 was 8.2% among children aged 6 to 7 years and 5% among adolescents aged between 13 and 14 years in Brazil; severe AD was present in 1.5% of children in both age groups.⁸

The main systemic therapies currently available for patients with severe AD are immunosuppressants, biologics, and small-molecule drugs. The considerable adverse effects of immunosuppressants limit their application. Dupilumab is considered the first-line treatment for children with severe AD. Clinical trials and case reports have demonstrated that dupilumab is effective in patients with AD, promoting notable improvement of pruritic eczematous lesions and quality-of-life scores.⁹ Dupilumab has been approved by the FDA for children older than 6 months, and some studies have shown up to a 49% reduction of pruritus in this age group.⁹ The main reported adverse effects were mild conjunctivitis and oral herpes simplex virus infection.^9,10

Upadacitinib is a reversible and selective JAK-1 inhibitor approved by the FDA for treatment of severe AD in patients aged 12 years and older. A multicenter, randomized, double-blind, placebo-controlled trial evaluated adolescents (12-17 years) and adults (18-75 years) with moderate to severe AD who were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.¹¹ A higher proportion of patients achieved an Eczema Area and Severity Index score of 75 at week 16 with both upadacitinib 15 mg daily (70%) and 30 mg daily (80%) compared to placebo. Improvements also were observed in both SCORAD and pruritus scores. The most commonly reported adverse events were acne, lipid profile abnormalities, and herpes zoster infection.¹¹

Our patient was a child with severe refractory AD that demonstrated a poor treatment response to dupilumab. When switched to off-label upadacitinib, her disease was effectively controlled; the treatment also was well tolerated with no adverse effects. Reports of upadacitinib used to treat AD in patients younger than 12 years are limited in the literature. One case report described a 9-year-old child with concurrent alopecia areata and severe AD who was successfully treated off label with upadacitinib.¹² A clinical trial also has evaluated the pharmacokinetics, safety, and tolerability of upadacitinib in children aged 2 to 12 years with severe AD (ClinicalTrials.gov Identifier: NCT03646604); although the trial was completed in 2024, at the time of this review (July 2025), the results have not been published.

Interestingly, there have been a few reports of adults with severe AD that failed to respond to treatment with immunosuppressants and dupilumab but showed notable clinical improvement when therapy was switched to upadacitinib,^13,14 as we noticed with our patient. These findings suggest that the JAK-STAT intracellular signaling pathway plays an important role in the pathogenesis of AD.

Continued development of safe and efficient targeted treatment for children with severe AD is critical. Upadacitinib was a safe and effective option for treatment of refractory and severe AD in our patient; however, further studies are needed to confirm both the efficacy and safety of JAK inhibitors in this age group.

To the Editor:

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is characterized by age-related morphology and distribution of lesions. Although AD can manifest at any age, it often develops during childhood, with an estimated worldwide prevalence of 15% to 25% in children and 1% to 10% in adults.¹ Clinical manifestation includes chronic or recurrent xerosis, pruritic eczematous lesions involving the flexural and extensor areas, and cutaneous infections. Immediate skin test reactivity and elevated total IgE levels can be found in up to 80% of patients.²

Although the pathogenesis of AD is complex, multifactorial, and not completely understood, some studies have highlighted the central role of a type 2 immune response, resulting in skin barrier dysfunction, cutaneous inflammation, and neuroimmune dysregulation.^3,4 The primary goals of treatment are to mitigate these factors through improvement of symptoms and long-term disease control. Topical emollients are used to repair the epidermal barrier, and topical anti-inflammatory therapy with corticosteroids or calcineurin inhibitors might be applied during flares; however, systemic treatment is essential for patients with moderate to severe AD that is not controlled with topical treatment or phototherapy.⁵

Until recently, systemic immunosuppressant agents such as corticosteroids, cyclosporine, and methotrexate were the only systemic treatment options for severe AD; however, their effectiveness is limited and they may cause serious long-term adverse events, limiting their regular usage, especially in children.⁶

Therapies that target type 2 immune responses include anti–IL-4/IL-13, anti–IL-13, and anti–IL-31 biologics. Dupilumab is a fully human monoclonal antibody targeting the type 2 immune response. This biologic directly binds to IL-4Rα,which prevents signaling by both the IL-4 and IL-13 pathways. Dupilumab was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD, with demonstrated efficacy and a favorable safety profile.⁵

In addition to biologics, Janus kinase (JAK) inhibitors belong to the small-molecule class. These drugs block the JAK/STAT intracellular signaling pathway, leading to inhibition of downstream effects triggered by several cytokines related to AD pathogenesis. Upadacitinib is an oral JAK inhibitor that was approved by the FDA in 2022 for treatment of severe AD in adults and children aged 12 years and older. This drug promotes a selective and reversible JAK-1 inhibition and has demonstrated rapid onset of action and a sustained reduction in the signs and symptoms of AD.⁷ We report the case of a child with recalcitrant severe AD that showed significant clinical improvement following off-label treatment with upadacitinib after showing a poor clinical response to dupilumab.

A 9-year-old girl presented to our pediatrics department with progressive worsening of severe AD over the previous 2 years. The patient had been diagnosed with AD at 6 months old, at which time she was treated with several prescribed moisturizers, topical and systemic corticosteroids, and calcineurin inhibitors with no clinical improvement.

The patient initially presented to us for evaluation of severe pruritus and associated sleep loss at age 7 years; physical examination revealed severe xerosis and disseminated pruritic eczematous lesions. Her SCORAD (SCORing Atopic Dermatitis) score was 70 (range, 0-103), and laboratory testing showed a high eosinophil count (1.5×10³/μL [range, 0-0.6×10³], 13%) and IgE level (1686 κU/L [range, 0-90]); a skin prick test on the forearm was positive for Blomia tropicalis.

Following her presentation with severe AD at 7 years old, the patient was prescribed systemic treatments including methotrexate and cyclosporine. During treatment with these agents, she presented to our department with several bacterial skin infections that required oral and intravenous antibiotics for treatment. These agents ultimately were discontinued after 12 months due to the adverse effects and poor clinical improvement. At age 8 years, the patient received an initial 600-mg dose of dupilumab followed by 300 mg subcutaneously every 4 weeks for 6 months along with topical corticosteroids and emollients. During treatment with dupilumab, the patient showed no clinical improvement (SCORAD score, 62). Therefore, we decided to change the dose to 200 mg every 2 weeks. The patient still showed no improvement and presented at age 9 years with moderate conjunctivitis and oculocutaneous infection caused by herpes simplex virus, which required treatment with oral acyclovir (Figure 1).

Considering the severe and refractory clinical course and the poor response to the recommended treatments for the patient’s age, oral upadacitinib was administered off label at a dose of 15 mg once daily after informed consent was obtained from her parents. She returned for follow-up once weekly for 1 month. Three days after starting treatment with upadacitinib, she showed considerable improvement in itch, and her SCORAD score decreased from 62 to 31 after 15 days. After 2 months of treatment, she reported no pruritus or sleep loss, and her SCORAD score was 4.5 (Figure 2). The results of a complete blood count, coagulation function test, and liver and kidney function tests were normal at 6-month and 12-month follow-up during upadacitinib therapy. No adverse effects were observed. The patient currently has completed 18 months of treatment, and the disease remains in complete remission.

Atopic dermatitis is highly prevalent in children. According to the International Study of Asthma and Allergies in Childhood, the prevalence of eczema in 2009 was 8.2% among children aged 6 to 7 years and 5% among adolescents aged between 13 and 14 years in Brazil; severe AD was present in 1.5% of children in both age groups.⁸

The main systemic therapies currently available for patients with severe AD are immunosuppressants, biologics, and small-molecule drugs. The considerable adverse effects of immunosuppressants limit their application. Dupilumab is considered the first-line treatment for children with severe AD. Clinical trials and case reports have demonstrated that dupilumab is effective in patients with AD, promoting notable improvement of pruritic eczematous lesions and quality-of-life scores.⁹ Dupilumab has been approved by the FDA for children older than 6 months, and some studies have shown up to a 49% reduction of pruritus in this age group.⁹ The main reported adverse effects were mild conjunctivitis and oral herpes simplex virus infection.^9,10

Upadacitinib is a reversible and selective JAK-1 inhibitor approved by the FDA for treatment of severe AD in patients aged 12 years and older. A multicenter, randomized, double-blind, placebo-controlled trial evaluated adolescents (12-17 years) and adults (18-75 years) with moderate to severe AD who were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.¹¹ A higher proportion of patients achieved an Eczema Area and Severity Index score of 75 at week 16 with both upadacitinib 15 mg daily (70%) and 30 mg daily (80%) compared to placebo. Improvements also were observed in both SCORAD and pruritus scores. The most commonly reported adverse events were acne, lipid profile abnormalities, and herpes zoster infection.¹¹

Our patient was a child with severe refractory AD that demonstrated a poor treatment response to dupilumab. When switched to off-label upadacitinib, her disease was effectively controlled; the treatment also was well tolerated with no adverse effects. Reports of upadacitinib used to treat AD in patients younger than 12 years are limited in the literature. One case report described a 9-year-old child with concurrent alopecia areata and severe AD who was successfully treated off label with upadacitinib.¹² A clinical trial also has evaluated the pharmacokinetics, safety, and tolerability of upadacitinib in children aged 2 to 12 years with severe AD (ClinicalTrials.gov Identifier: NCT03646604); although the trial was completed in 2024, at the time of this review (July 2025), the results have not been published.

Interestingly, there have been a few reports of adults with severe AD that failed to respond to treatment with immunosuppressants and dupilumab but showed notable clinical improvement when therapy was switched to upadacitinib,^13,14 as we noticed with our patient. These findings suggest that the JAK-STAT intracellular signaling pathway plays an important role in the pathogenesis of AD.

Continued development of safe and efficient targeted treatment for children with severe AD is critical. Upadacitinib was a safe and effective option for treatment of refractory and severe AD in our patient; however, further studies are needed to confirm both the efficacy and safety of JAK inhibitors in this age group.

To the Editor:

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is characterized by age-related morphology and distribution of lesions. Although AD can manifest at any age, it often develops during childhood, with an estimated worldwide prevalence of 15% to 25% in children and 1% to 10% in adults.¹ Clinical manifestation includes chronic or recurrent xerosis, pruritic eczematous lesions involving the flexural and extensor areas, and cutaneous infections. Immediate skin test reactivity and elevated total IgE levels can be found in up to 80% of patients.²

Although the pathogenesis of AD is complex, multifactorial, and not completely understood, some studies have highlighted the central role of a type 2 immune response, resulting in skin barrier dysfunction, cutaneous inflammation, and neuroimmune dysregulation.^3,4 The primary goals of treatment are to mitigate these factors through improvement of symptoms and long-term disease control. Topical emollients are used to repair the epidermal barrier, and topical anti-inflammatory therapy with corticosteroids or calcineurin inhibitors might be applied during flares; however, systemic treatment is essential for patients with moderate to severe AD that is not controlled with topical treatment or phototherapy.⁵

Until recently, systemic immunosuppressant agents such as corticosteroids, cyclosporine, and methotrexate were the only systemic treatment options for severe AD; however, their effectiveness is limited and they may cause serious long-term adverse events, limiting their regular usage, especially in children.⁶

Therapies that target type 2 immune responses include anti–IL-4/IL-13, anti–IL-13, and anti–IL-31 biologics. Dupilumab is a fully human monoclonal antibody targeting the type 2 immune response. This biologic directly binds to IL-4Rα,which prevents signaling by both the IL-4 and IL-13 pathways. Dupilumab was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD, with demonstrated efficacy and a favorable safety profile.⁵

In addition to biologics, Janus kinase (JAK) inhibitors belong to the small-molecule class. These drugs block the JAK/STAT intracellular signaling pathway, leading to inhibition of downstream effects triggered by several cytokines related to AD pathogenesis. Upadacitinib is an oral JAK inhibitor that was approved by the FDA in 2022 for treatment of severe AD in adults and children aged 12 years and older. This drug promotes a selective and reversible JAK-1 inhibition and has demonstrated rapid onset of action and a sustained reduction in the signs and symptoms of AD.⁷ We report the case of a child with recalcitrant severe AD that showed significant clinical improvement following off-label treatment with upadacitinib after showing a poor clinical response to dupilumab.

A 9-year-old girl presented to our pediatrics department with progressive worsening of severe AD over the previous 2 years. The patient had been diagnosed with AD at 6 months old, at which time she was treated with several prescribed moisturizers, topical and systemic corticosteroids, and calcineurin inhibitors with no clinical improvement.

The patient initially presented to us for evaluation of severe pruritus and associated sleep loss at age 7 years; physical examination revealed severe xerosis and disseminated pruritic eczematous lesions. Her SCORAD (SCORing Atopic Dermatitis) score was 70 (range, 0-103), and laboratory testing showed a high eosinophil count (1.5×10³/μL [range, 0-0.6×10³], 13%) and IgE level (1686 κU/L [range, 0-90]); a skin prick test on the forearm was positive for Blomia tropicalis.

Following her presentation with severe AD at 7 years old, the patient was prescribed systemic treatments including methotrexate and cyclosporine. During treatment with these agents, she presented to our department with several bacterial skin infections that required oral and intravenous antibiotics for treatment. These agents ultimately were discontinued after 12 months due to the adverse effects and poor clinical improvement. At age 8 years, the patient received an initial 600-mg dose of dupilumab followed by 300 mg subcutaneously every 4 weeks for 6 months along with topical corticosteroids and emollients. During treatment with dupilumab, the patient showed no clinical improvement (SCORAD score, 62). Therefore, we decided to change the dose to 200 mg every 2 weeks. The patient still showed no improvement and presented at age 9 years with moderate conjunctivitis and oculocutaneous infection caused by herpes simplex virus, which required treatment with oral acyclovir (Figure 1).

Considering the severe and refractory clinical course and the poor response to the recommended treatments for the patient’s age, oral upadacitinib was administered off label at a dose of 15 mg once daily after informed consent was obtained from her parents. She returned for follow-up once weekly for 1 month. Three days after starting treatment with upadacitinib, she showed considerable improvement in itch, and her SCORAD score decreased from 62 to 31 after 15 days. After 2 months of treatment, she reported no pruritus or sleep loss, and her SCORAD score was 4.5 (Figure 2). The results of a complete blood count, coagulation function test, and liver and kidney function tests were normal at 6-month and 12-month follow-up during upadacitinib therapy. No adverse effects were observed. The patient currently has completed 18 months of treatment, and the disease remains in complete remission.

Atopic dermatitis is highly prevalent in children. According to the International Study of Asthma and Allergies in Childhood, the prevalence of eczema in 2009 was 8.2% among children aged 6 to 7 years and 5% among adolescents aged between 13 and 14 years in Brazil; severe AD was present in 1.5% of children in both age groups.⁸

The main systemic therapies currently available for patients with severe AD are immunosuppressants, biologics, and small-molecule drugs. The considerable adverse effects of immunosuppressants limit their application. Dupilumab is considered the first-line treatment for children with severe AD. Clinical trials and case reports have demonstrated that dupilumab is effective in patients with AD, promoting notable improvement of pruritic eczematous lesions and quality-of-life scores.⁹ Dupilumab has been approved by the FDA for children older than 6 months, and some studies have shown up to a 49% reduction of pruritus in this age group.⁹ The main reported adverse effects were mild conjunctivitis and oral herpes simplex virus infection.^9,10

Upadacitinib is a reversible and selective JAK-1 inhibitor approved by the FDA for treatment of severe AD in patients aged 12 years and older. A multicenter, randomized, double-blind, placebo-controlled trial evaluated adolescents (12-17 years) and adults (18-75 years) with moderate to severe AD who were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.¹¹ A higher proportion of patients achieved an Eczema Area and Severity Index score of 75 at week 16 with both upadacitinib 15 mg daily (70%) and 30 mg daily (80%) compared to placebo. Improvements also were observed in both SCORAD and pruritus scores. The most commonly reported adverse events were acne, lipid profile abnormalities, and herpes zoster infection.¹¹

Our patient was a child with severe refractory AD that demonstrated a poor treatment response to dupilumab. When switched to off-label upadacitinib, her disease was effectively controlled; the treatment also was well tolerated with no adverse effects. Reports of upadacitinib used to treat AD in patients younger than 12 years are limited in the literature. One case report described a 9-year-old child with concurrent alopecia areata and severe AD who was successfully treated off label with upadacitinib.¹² A clinical trial also has evaluated the pharmacokinetics, safety, and tolerability of upadacitinib in children aged 2 to 12 years with severe AD (ClinicalTrials.gov Identifier: NCT03646604); although the trial was completed in 2024, at the time of this review (July 2025), the results have not been published.

Interestingly, there have been a few reports of adults with severe AD that failed to respond to treatment with immunosuppressants and dupilumab but showed notable clinical improvement when therapy was switched to upadacitinib,^13,14 as we noticed with our patient. These findings suggest that the JAK-STAT intracellular signaling pathway plays an important role in the pathogenesis of AD.

Continued development of safe and efficient targeted treatment for children with severe AD is critical. Upadacitinib was a safe and effective option for treatment of refractory and severe AD in our patient; however, further studies are needed to confirm both the efficacy and safety of JAK inhibitors in this age group.

THE DIAGNOSIS: Pedunculated Lipofibroma

Histopathology confirmed a pedunculated/polypoid lesion with intradermal lobules of adipocytes/mature adipose tissue admixed with connective tissue bundles and vascular ectasias. Overlying epidermal acanthosis with slight papillomatosis and hyperkeratosis was present (Figure 1). Masson trichrome staining highlighted admixed collagen bundles (Figure 2). Verhoeff–van Gieson staining showed marked reduction in elastic fibers (Figure 3). Immunostaining was negative for smooth muscle actin and desmin. A diagnosis of pedunculated lipofibroma on the nose was made based on both clinical and histopathologic findings.

Pedunculated lipofibroma (or solitary lipofibroma) is the solitary form of nevus lipomatosus cutaneous superficialis (NLCS).⁷ First described by Hoffmann and Zurhelle¹ in 1921, NLCS is an uncommon benign hamartomatous cutaneous lesion/connective tissue nevus that also has a classic multiple form.^1-13 The etiology of NLCS remains unclear, but several theories have been proposed to explain its pathogenesis, including deposition of adipocytes secondary to degenerative changes in dermal connective tissue, focal/local heterotopic development of adipose tissue, and derivation from differentiating lipoblasts (preadipose tissue) originating from precursor vascular or perivascular cells.^2-13

Pedunculated lipofibroma usually develops during the third to sixth decades of life and manifests as a single cutaneous lesion with a smooth surface, often on a non–pelvic girdle location.^7-13 No particular predilection sites are noted, with lesions reported on the arm, axilla, back, upper thigh, knee, and sole.^5,12 There are rare reports of this type of NLCS on the ear, scalp, forehead, or eyelid.^7-11

In the classic form of NLCS, multiple cutaneous lesions are present at birth or develop within the first 2 to 3 decades of life.^2-6 Lesions consist of soft, nontender, pedunculated, flesh-colored or yellowish papules and nodules with a verrucoid or cerebriform surface that may later coalesce to form plaques.^2-6 Predilection sites include the pelvic girdle, buttocks, sacral and coccygeal regions, and upper posterior thighs, with a linear or zosteriform pattern of distribution.^2-6 Rarely, the classic form can arise in elderly patients and/or at an atypical anatomic location (eg, clitoris,³ shoulder,⁵ thorax,⁵ abdomen⁵) and can demonstrate extension of lesions across the midline.⁴ Rare cases of classic NLCS on the scalp² and face^3-6 have been reported, including lesions localized to the nose³ and chin⁴ and others extending from the right mandible to the neck⁵ and right lower lip to the submandibular/posteriorateral cervical region.⁶ In some cases, lesions clinically resemble plane xanthoma⁴ and localized scleroderma.⁶

Adotama et al¹³ proposed a set of clinical features to differentiate classic NLCS, pedunculated lipofibroma (solitary NLCS), and fibroepithelial polyp with adipocytes (distinguished by their furrowed surface, hyperpigmentation, and anatomic predilection for the neck and axilla). Lesions are asymptomatic in both forms of NLCS.^2-13 Family history or predominant sex involvement have not been reported in either clinical type.^2-13 Reported associations with NLCS include a number of endocrinologic conditions including diabetes.⁷ Other coexisting skin findings can include café-au-lait macules, leukodermic (white) spots, overlying hypertrichosis, comedolike alterations, angiokeratoma, hemangioma, and folliculosebaceous cystic hamartoma.⁴ None of these were evident in our patient.

Lesions from both types of NLCS are indistinguishable on histopathology, characterized by the presence of a central core of ectopic mature adipocytes in the papillary/reticular dermis.^2-13 Additional light microscopic features (some seen in our case) have been described, including thickened collagen bundles, reduction of elastic fibers, increased numbers of fibroblasts and/or mast cells, increased (small-vessel) vascularity, focal mucin deposition/myxoid degeneration, a mild perivascular lymphocytic infiltrate, attenuation of adnexal structures, and abnormalities of the epidermis (eg, surface ulceration).^2-13

Prior to biopsy, the differential diagnosis in our patient included angiofibroma, pyogenic granuloma, and basal cell carcinoma given the exophytic, pink, papular appearance of the lesion; however, the histopathologic differential diagnosis included angiofibroma, angiomyolipoma, lymphangioma, nevus sebaceus, and spindle cell lipoma (SCL). In angiofibroma, a dermal proliferation of stellate fibroblasts, dilated blood vessels, and collagenous stroma are seen. Cutaneous angiomyolipoma demonstrates smooth muscle bundles in addition to thickened blood vessels and variable proportions of mature adipocytes. Lymphangioma is characterized by dilated lymph channels lined by flat endothelial cells. Nevus sebaceus shows superficial immature and abnormally formed pilosebaceous units, with epidermal papillomatosis.

Rare cases of SCL on the nose have been described.¹⁴ Similar to pedunculated lipofibroma, reported examples demonstrate mature univacuolar adipocytes with thick collagen fibers and bland uniform spindle cells. Unlike the lesion seen in our patient, nasal SCL may be clinically mobile and typically is localized to the subcutaneous tissue, although dermal tumors also occur.¹⁴ Variably reported histopathologic findings in nasal SCL include circumscription/encapsulation, spindle cells arranged in short fascicles with nuclear palisading, a myxoid/mucinous interstitial matrix, and/or multinucleated giant cells—all light microscopic features that were not identified in our case; however, variable proportions of adipocytic, fibrous, and myxoid components among reported examples of SCL on the nose¹⁴ can make distinction from pedunculated lipofibroma difficult, as both are benign lipomatous tumor variants.

Clinically, pedunculated lipofibroma may be confused with more common benign cutaneous lesions and must be distinguished from other fibrolipomatous lesions on the nose. Specifically, the differential diagnosis includes benign cutaneous papillomas such as acrochordon, angiofibroma, melanocytic nevi, neurofibroma, nevus sebaceus, lymphangioma, and eccrine poroma.^7-13 These all can be readily excluded on histopathology. Pedunculated lipofibroma on the nose, as in our patient, must be distinguished from fibrolipoma¹⁵ and dendritic myxofibrolipoma.¹⁶ Fibrolipoma is a subcutaneous proliferation of mature adipose tissue and fibrous tissue and comprises 1.6% of all facial lipomas reported worldwide.¹⁵ Dendritic myxofibrolipoma is a recently described benign soft-tissue tumor characterized by an admixture of mature adipose tissue, spindle and stellate cells, and an abundant myxoid stroma with prominent collagenization.¹⁶

Treatment of pedunculated lipofibroma on the nose is not indicated except for cosmetic reasons, in which case simple surgical excision would be considered satisfactory. Following biopsy, no further treatment was pursued in our patient.

THE DIAGNOSIS: Pedunculated Lipofibroma

Histopathology confirmed a pedunculated/polypoid lesion with intradermal lobules of adipocytes/mature adipose tissue admixed with connective tissue bundles and vascular ectasias. Overlying epidermal acanthosis with slight papillomatosis and hyperkeratosis was present (Figure 1). Masson trichrome staining highlighted admixed collagen bundles (Figure 2). Verhoeff–van Gieson staining showed marked reduction in elastic fibers (Figure 3). Immunostaining was negative for smooth muscle actin and desmin. A diagnosis of pedunculated lipofibroma on the nose was made based on both clinical and histopathologic findings.

Pedunculated lipofibroma (or solitary lipofibroma) is the solitary form of nevus lipomatosus cutaneous superficialis (NLCS).⁷ First described by Hoffmann and Zurhelle¹ in 1921, NLCS is an uncommon benign hamartomatous cutaneous lesion/connective tissue nevus that also has a classic multiple form.^1-13 The etiology of NLCS remains unclear, but several theories have been proposed to explain its pathogenesis, including deposition of adipocytes secondary to degenerative changes in dermal connective tissue, focal/local heterotopic development of adipose tissue, and derivation from differentiating lipoblasts (preadipose tissue) originating from precursor vascular or perivascular cells.^2-13

Pedunculated lipofibroma usually develops during the third to sixth decades of life and manifests as a single cutaneous lesion with a smooth surface, often on a non–pelvic girdle location.^7-13 No particular predilection sites are noted, with lesions reported on the arm, axilla, back, upper thigh, knee, and sole.^5,12 There are rare reports of this type of NLCS on the ear, scalp, forehead, or eyelid.^7-11

In the classic form of NLCS, multiple cutaneous lesions are present at birth or develop within the first 2 to 3 decades of life.^2-6 Lesions consist of soft, nontender, pedunculated, flesh-colored or yellowish papules and nodules with a verrucoid or cerebriform surface that may later coalesce to form plaques.^2-6 Predilection sites include the pelvic girdle, buttocks, sacral and coccygeal regions, and upper posterior thighs, with a linear or zosteriform pattern of distribution.^2-6 Rarely, the classic form can arise in elderly patients and/or at an atypical anatomic location (eg, clitoris,³ shoulder,⁵ thorax,⁵ abdomen⁵) and can demonstrate extension of lesions across the midline.⁴ Rare cases of classic NLCS on the scalp² and face^3-6 have been reported, including lesions localized to the nose³ and chin⁴ and others extending from the right mandible to the neck⁵ and right lower lip to the submandibular/posteriorateral cervical region.⁶ In some cases, lesions clinically resemble plane xanthoma⁴ and localized scleroderma.⁶

Adotama et al¹³ proposed a set of clinical features to differentiate classic NLCS, pedunculated lipofibroma (solitary NLCS), and fibroepithelial polyp with adipocytes (distinguished by their furrowed surface, hyperpigmentation, and anatomic predilection for the neck and axilla). Lesions are asymptomatic in both forms of NLCS.^2-13 Family history or predominant sex involvement have not been reported in either clinical type.^2-13 Reported associations with NLCS include a number of endocrinologic conditions including diabetes.⁷ Other coexisting skin findings can include café-au-lait macules, leukodermic (white) spots, overlying hypertrichosis, comedolike alterations, angiokeratoma, hemangioma, and folliculosebaceous cystic hamartoma.⁴ None of these were evident in our patient.

Lesions from both types of NLCS are indistinguishable on histopathology, characterized by the presence of a central core of ectopic mature adipocytes in the papillary/reticular dermis.^2-13 Additional light microscopic features (some seen in our case) have been described, including thickened collagen bundles, reduction of elastic fibers, increased numbers of fibroblasts and/or mast cells, increased (small-vessel) vascularity, focal mucin deposition/myxoid degeneration, a mild perivascular lymphocytic infiltrate, attenuation of adnexal structures, and abnormalities of the epidermis (eg, surface ulceration).^2-13

Prior to biopsy, the differential diagnosis in our patient included angiofibroma, pyogenic granuloma, and basal cell carcinoma given the exophytic, pink, papular appearance of the lesion; however, the histopathologic differential diagnosis included angiofibroma, angiomyolipoma, lymphangioma, nevus sebaceus, and spindle cell lipoma (SCL). In angiofibroma, a dermal proliferation of stellate fibroblasts, dilated blood vessels, and collagenous stroma are seen. Cutaneous angiomyolipoma demonstrates smooth muscle bundles in addition to thickened blood vessels and variable proportions of mature adipocytes. Lymphangioma is characterized by dilated lymph channels lined by flat endothelial cells. Nevus sebaceus shows superficial immature and abnormally formed pilosebaceous units, with epidermal papillomatosis.

Rare cases of SCL on the nose have been described.¹⁴ Similar to pedunculated lipofibroma, reported examples demonstrate mature univacuolar adipocytes with thick collagen fibers and bland uniform spindle cells. Unlike the lesion seen in our patient, nasal SCL may be clinically mobile and typically is localized to the subcutaneous tissue, although dermal tumors also occur.¹⁴ Variably reported histopathologic findings in nasal SCL include circumscription/encapsulation, spindle cells arranged in short fascicles with nuclear palisading, a myxoid/mucinous interstitial matrix, and/or multinucleated giant cells—all light microscopic features that were not identified in our case; however, variable proportions of adipocytic, fibrous, and myxoid components among reported examples of SCL on the nose¹⁴ can make distinction from pedunculated lipofibroma difficult, as both are benign lipomatous tumor variants.

Clinically, pedunculated lipofibroma may be confused with more common benign cutaneous lesions and must be distinguished from other fibrolipomatous lesions on the nose. Specifically, the differential diagnosis includes benign cutaneous papillomas such as acrochordon, angiofibroma, melanocytic nevi, neurofibroma, nevus sebaceus, lymphangioma, and eccrine poroma.^7-13 These all can be readily excluded on histopathology. Pedunculated lipofibroma on the nose, as in our patient, must be distinguished from fibrolipoma¹⁵ and dendritic myxofibrolipoma.¹⁶ Fibrolipoma is a subcutaneous proliferation of mature adipose tissue and fibrous tissue and comprises 1.6% of all facial lipomas reported worldwide.¹⁵ Dendritic myxofibrolipoma is a recently described benign soft-tissue tumor characterized by an admixture of mature adipose tissue, spindle and stellate cells, and an abundant myxoid stroma with prominent collagenization.¹⁶

Treatment of pedunculated lipofibroma on the nose is not indicated except for cosmetic reasons, in which case simple surgical excision would be considered satisfactory. Following biopsy, no further treatment was pursued in our patient.

THE DIAGNOSIS: Pedunculated Lipofibroma

Histopathology confirmed a pedunculated/polypoid lesion with intradermal lobules of adipocytes/mature adipose tissue admixed with connective tissue bundles and vascular ectasias. Overlying epidermal acanthosis with slight papillomatosis and hyperkeratosis was present (Figure 1). Masson trichrome staining highlighted admixed collagen bundles (Figure 2). Verhoeff–van Gieson staining showed marked reduction in elastic fibers (Figure 3). Immunostaining was negative for smooth muscle actin and desmin. A diagnosis of pedunculated lipofibroma on the nose was made based on both clinical and histopathologic findings.

Pedunculated lipofibroma (or solitary lipofibroma) is the solitary form of nevus lipomatosus cutaneous superficialis (NLCS).⁷ First described by Hoffmann and Zurhelle¹ in 1921, NLCS is an uncommon benign hamartomatous cutaneous lesion/connective tissue nevus that also has a classic multiple form.^1-13 The etiology of NLCS remains unclear, but several theories have been proposed to explain its pathogenesis, including deposition of adipocytes secondary to degenerative changes in dermal connective tissue, focal/local heterotopic development of adipose tissue, and derivation from differentiating lipoblasts (preadipose tissue) originating from precursor vascular or perivascular cells.^2-13

Pedunculated lipofibroma usually develops during the third to sixth decades of life and manifests as a single cutaneous lesion with a smooth surface, often on a non–pelvic girdle location.^7-13 No particular predilection sites are noted, with lesions reported on the arm, axilla, back, upper thigh, knee, and sole.^5,12 There are rare reports of this type of NLCS on the ear, scalp, forehead, or eyelid.^7-11

In the classic form of NLCS, multiple cutaneous lesions are present at birth or develop within the first 2 to 3 decades of life.^2-6 Lesions consist of soft, nontender, pedunculated, flesh-colored or yellowish papules and nodules with a verrucoid or cerebriform surface that may later coalesce to form plaques.^2-6 Predilection sites include the pelvic girdle, buttocks, sacral and coccygeal regions, and upper posterior thighs, with a linear or zosteriform pattern of distribution.^2-6 Rarely, the classic form can arise in elderly patients and/or at an atypical anatomic location (eg, clitoris,³ shoulder,⁵ thorax,⁵ abdomen⁵) and can demonstrate extension of lesions across the midline.⁴ Rare cases of classic NLCS on the scalp² and face^3-6 have been reported, including lesions localized to the nose³ and chin⁴ and others extending from the right mandible to the neck⁵ and right lower lip to the submandibular/posteriorateral cervical region.⁶ In some cases, lesions clinically resemble plane xanthoma⁴ and localized scleroderma.⁶

Adotama et al¹³ proposed a set of clinical features to differentiate classic NLCS, pedunculated lipofibroma (solitary NLCS), and fibroepithelial polyp with adipocytes (distinguished by their furrowed surface, hyperpigmentation, and anatomic predilection for the neck and axilla). Lesions are asymptomatic in both forms of NLCS.^2-13 Family history or predominant sex involvement have not been reported in either clinical type.^2-13 Reported associations with NLCS include a number of endocrinologic conditions including diabetes.⁷ Other coexisting skin findings can include café-au-lait macules, leukodermic (white) spots, overlying hypertrichosis, comedolike alterations, angiokeratoma, hemangioma, and folliculosebaceous cystic hamartoma.⁴ None of these were evident in our patient.

Lesions from both types of NLCS are indistinguishable on histopathology, characterized by the presence of a central core of ectopic mature adipocytes in the papillary/reticular dermis.^2-13 Additional light microscopic features (some seen in our case) have been described, including thickened collagen bundles, reduction of elastic fibers, increased numbers of fibroblasts and/or mast cells, increased (small-vessel) vascularity, focal mucin deposition/myxoid degeneration, a mild perivascular lymphocytic infiltrate, attenuation of adnexal structures, and abnormalities of the epidermis (eg, surface ulceration).^2-13

Prior to biopsy, the differential diagnosis in our patient included angiofibroma, pyogenic granuloma, and basal cell carcinoma given the exophytic, pink, papular appearance of the lesion; however, the histopathologic differential diagnosis included angiofibroma, angiomyolipoma, lymphangioma, nevus sebaceus, and spindle cell lipoma (SCL). In angiofibroma, a dermal proliferation of stellate fibroblasts, dilated blood vessels, and collagenous stroma are seen. Cutaneous angiomyolipoma demonstrates smooth muscle bundles in addition to thickened blood vessels and variable proportions of mature adipocytes. Lymphangioma is characterized by dilated lymph channels lined by flat endothelial cells. Nevus sebaceus shows superficial immature and abnormally formed pilosebaceous units, with epidermal papillomatosis.

Rare cases of SCL on the nose have been described.¹⁴ Similar to pedunculated lipofibroma, reported examples demonstrate mature univacuolar adipocytes with thick collagen fibers and bland uniform spindle cells. Unlike the lesion seen in our patient, nasal SCL may be clinically mobile and typically is localized to the subcutaneous tissue, although dermal tumors also occur.¹⁴ Variably reported histopathologic findings in nasal SCL include circumscription/encapsulation, spindle cells arranged in short fascicles with nuclear palisading, a myxoid/mucinous interstitial matrix, and/or multinucleated giant cells—all light microscopic features that were not identified in our case; however, variable proportions of adipocytic, fibrous, and myxoid components among reported examples of SCL on the nose¹⁴ can make distinction from pedunculated lipofibroma difficult, as both are benign lipomatous tumor variants.

Clinically, pedunculated lipofibroma may be confused with more common benign cutaneous lesions and must be distinguished from other fibrolipomatous lesions on the nose. Specifically, the differential diagnosis includes benign cutaneous papillomas such as acrochordon, angiofibroma, melanocytic nevi, neurofibroma, nevus sebaceus, lymphangioma, and eccrine poroma.^7-13 These all can be readily excluded on histopathology. Pedunculated lipofibroma on the nose, as in our patient, must be distinguished from fibrolipoma¹⁵ and dendritic myxofibrolipoma.¹⁶ Fibrolipoma is a subcutaneous proliferation of mature adipose tissue and fibrous tissue and comprises 1.6% of all facial lipomas reported worldwide.¹⁵ Dendritic myxofibrolipoma is a recently described benign soft-tissue tumor characterized by an admixture of mature adipose tissue, spindle and stellate cells, and an abundant myxoid stroma with prominent collagenization.¹⁶

Treatment of pedunculated lipofibroma on the nose is not indicated except for cosmetic reasons, in which case simple surgical excision would be considered satisfactory. Following biopsy, no further treatment was pursued in our patient.

To the Editor:

Drug-induced hyperpigmentation is a common cause of an acquired increase in pigmentation. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK2) that is approved for the treatment of chronic graft-vs-host disease (GVHD). We describe a patient who developed diffuse skin bronzing 3 weeks after initiation of belumosudil treatment.

A 64-year-old fair-skinned woman presented to the dermatology clinic with bronzing of the skin and dystrophic nails 3 weeks after starting belumosudil for treatment of chronic GVHD. Six months prior to presentation, the patient had received a bone marrow transplant for chronic lymphoid leukemia. She presented to dermatology 6 months after the transplant with a new-onset rash that was suspicious for GVHD. Physical examination revealed pruritic pink papules diffusely scattered on the legs and forearms (Figure 1). The patient declined biopsy at that time and later followed up with oncology. The patient’s oncologist supported a diagnosis of GVHD, and the patient began treatment with belumosudil 200 mg/d which was intended to be taken until treatment failure due to progression of chronic GVHD.

Three weeks after starting belumosudil, the patient developed diffuse bronzing of the skin and brown, evenly colored patches scattered on the trunk, back, and upper and lower extremities on a background of the presumed GVHD rash (Figure 2). The hyperpigmentation was abrupt, starting on the chest and spreading to the abdomen, extremities, and back (Figure 3).

Again, the patient was offered biopsy for the new-onset pigmentation but declined. During this time, she had no notable sun exposure and primarily stayed indoors despite living in a region with a sunny semi-arid climate. Her medication and supplement list were reviewed and included acalabrutinib, a multivitamin, lutein, biotin, and a fish oil supplement. A compete blood cell count as well as ferritin, transferrin, cortisol, and adrenocorticotropic hormone levels were unremarkable.

The patient continued to take belumosudil for treatment of GVHD. The hyperpigmentation faded slightly by a 2-month follow-up visit but persisted and was stable. She has not tried other treatments for GVHD to manage the hyperpigmentation.

Conditions known to cause diffuse bronzing of the skin include Addison disease, hemochromatosis, Cushing disease, and medication adverse events. Our patient presented with an absence of systemic symptoms, normal laboratory results, and no clinical indicators suggesting alternate causes. Given that the onset of the hyperpigmentation was 3 weeks after she started a new medication, we hypothesized that the bronzing was an adverse effect of the belumosudil—though this correlation cannot be definitively proven by this case.

The most common offending agents for drug-induced skin hyperpigmentation are nonsteroidal anti- inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, and tetracyclines.^1,2 Our patient’s medication list included the cytotoxic agent acalabrutinib, a Bruton tyrosine kinase inhibitor used for the treatment of non-Hodgkin lymphoma. It has been associated with dermatologic findings of ecchymosis, bruising, panniculitis, and cellulitis, but there are no known reports of hyperpigmentation.³ Our patient had been taking acalabrutinib for 6 months when the GVHD rash developed. At the time, she also was taking a multivitamin and lutein, biotin, and fish oil supplements, none of which have been associated with hyperpigmentation.

Polypharmacy adds a layer of difficulty in identifying the inciting cause of pigmentary change. In our case, symptoms began 3 weeks after the initiation of belumosudil. There were no cutaneous reactions observed in the ROCKstar study of belumosudil; the most common adverse events were upper respiratory tract infection, diarrhea, fatigue, nausea, increased liver enzymes, and dyspnea.^4,5 Patients on belumosudil have developed aggressive cutaneous squamous cell carcinoma.⁶ However, a search of PubMed articles indexed for MEDLINE using the search terms acalabrutinib or belumosudil with hyperpigmentation or cutaneous reaction returned no reports of these medications causing hyperpigmentation or cutaneous deposits.

Treatment of drug-induced hyperpigmentation is difficult because discontinuation of the offending agent typically confirms diagnosis, but interruption of treatment is not always possible, as in our patient. The skin changes can fade over time, but effects typically are long lasting.

Dermatologists play a key role in the identification of drug-induced skin hyperpigmentation. After endocrine or metabolic causes of skin hyperpigmentation have been ruled out, a thorough review of the patient’s medication list should be done to assess for a drug-induced cause. Treatment is limited to sun avoidance, as interruption of treatment may not be possible, and lesions typically do fade over time. These chronic skin changes can have a psychosocial effect on patients and regular follow-up is recommended.

To the Editor:

Drug-induced hyperpigmentation is a common cause of an acquired increase in pigmentation. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK2) that is approved for the treatment of chronic graft-vs-host disease (GVHD). We describe a patient who developed diffuse skin bronzing 3 weeks after initiation of belumosudil treatment.

A 64-year-old fair-skinned woman presented to the dermatology clinic with bronzing of the skin and dystrophic nails 3 weeks after starting belumosudil for treatment of chronic GVHD. Six months prior to presentation, the patient had received a bone marrow transplant for chronic lymphoid leukemia. She presented to dermatology 6 months after the transplant with a new-onset rash that was suspicious for GVHD. Physical examination revealed pruritic pink papules diffusely scattered on the legs and forearms (Figure 1). The patient declined biopsy at that time and later followed up with oncology. The patient’s oncologist supported a diagnosis of GVHD, and the patient began treatment with belumosudil 200 mg/d which was intended to be taken until treatment failure due to progression of chronic GVHD.

Three weeks after starting belumosudil, the patient developed diffuse bronzing of the skin and brown, evenly colored patches scattered on the trunk, back, and upper and lower extremities on a background of the presumed GVHD rash (Figure 2). The hyperpigmentation was abrupt, starting on the chest and spreading to the abdomen, extremities, and back (Figure 3).

Again, the patient was offered biopsy for the new-onset pigmentation but declined. During this time, she had no notable sun exposure and primarily stayed indoors despite living in a region with a sunny semi-arid climate. Her medication and supplement list were reviewed and included acalabrutinib, a multivitamin, lutein, biotin, and a fish oil supplement. A compete blood cell count as well as ferritin, transferrin, cortisol, and adrenocorticotropic hormone levels were unremarkable.

The patient continued to take belumosudil for treatment of GVHD. The hyperpigmentation faded slightly by a 2-month follow-up visit but persisted and was stable. She has not tried other treatments for GVHD to manage the hyperpigmentation.

Conditions known to cause diffuse bronzing of the skin include Addison disease, hemochromatosis, Cushing disease, and medication adverse events. Our patient presented with an absence of systemic symptoms, normal laboratory results, and no clinical indicators suggesting alternate causes. Given that the onset of the hyperpigmentation was 3 weeks after she started a new medication, we hypothesized that the bronzing was an adverse effect of the belumosudil—though this correlation cannot be definitively proven by this case.

The most common offending agents for drug-induced skin hyperpigmentation are nonsteroidal anti- inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, and tetracyclines.^1,2 Our patient’s medication list included the cytotoxic agent acalabrutinib, a Bruton tyrosine kinase inhibitor used for the treatment of non-Hodgkin lymphoma. It has been associated with dermatologic findings of ecchymosis, bruising, panniculitis, and cellulitis, but there are no known reports of hyperpigmentation.³ Our patient had been taking acalabrutinib for 6 months when the GVHD rash developed. At the time, she also was taking a multivitamin and lutein, biotin, and fish oil supplements, none of which have been associated with hyperpigmentation.

Polypharmacy adds a layer of difficulty in identifying the inciting cause of pigmentary change. In our case, symptoms began 3 weeks after the initiation of belumosudil. There were no cutaneous reactions observed in the ROCKstar study of belumosudil; the most common adverse events were upper respiratory tract infection, diarrhea, fatigue, nausea, increased liver enzymes, and dyspnea.^4,5 Patients on belumosudil have developed aggressive cutaneous squamous cell carcinoma.⁶ However, a search of PubMed articles indexed for MEDLINE using the search terms acalabrutinib or belumosudil with hyperpigmentation or cutaneous reaction returned no reports of these medications causing hyperpigmentation or cutaneous deposits.

Treatment of drug-induced hyperpigmentation is difficult because discontinuation of the offending agent typically confirms diagnosis, but interruption of treatment is not always possible, as in our patient. The skin changes can fade over time, but effects typically are long lasting.

Dermatologists play a key role in the identification of drug-induced skin hyperpigmentation. After endocrine or metabolic causes of skin hyperpigmentation have been ruled out, a thorough review of the patient’s medication list should be done to assess for a drug-induced cause. Treatment is limited to sun avoidance, as interruption of treatment may not be possible, and lesions typically do fade over time. These chronic skin changes can have a psychosocial effect on patients and regular follow-up is recommended.

To the Editor:

Drug-induced hyperpigmentation is a common cause of an acquired increase in pigmentation. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK2) that is approved for the treatment of chronic graft-vs-host disease (GVHD). We describe a patient who developed diffuse skin bronzing 3 weeks after initiation of belumosudil treatment.

A 64-year-old fair-skinned woman presented to the dermatology clinic with bronzing of the skin and dystrophic nails 3 weeks after starting belumosudil for treatment of chronic GVHD. Six months prior to presentation, the patient had received a bone marrow transplant for chronic lymphoid leukemia. She presented to dermatology 6 months after the transplant with a new-onset rash that was suspicious for GVHD. Physical examination revealed pruritic pink papules diffusely scattered on the legs and forearms (Figure 1). The patient declined biopsy at that time and later followed up with oncology. The patient’s oncologist supported a diagnosis of GVHD, and the patient began treatment with belumosudil 200 mg/d which was intended to be taken until treatment failure due to progression of chronic GVHD.

Three weeks after starting belumosudil, the patient developed diffuse bronzing of the skin and brown, evenly colored patches scattered on the trunk, back, and upper and lower extremities on a background of the presumed GVHD rash (Figure 2). The hyperpigmentation was abrupt, starting on the chest and spreading to the abdomen, extremities, and back (Figure 3).

Again, the patient was offered biopsy for the new-onset pigmentation but declined. During this time, she had no notable sun exposure and primarily stayed indoors despite living in a region with a sunny semi-arid climate. Her medication and supplement list were reviewed and included acalabrutinib, a multivitamin, lutein, biotin, and a fish oil supplement. A compete blood cell count as well as ferritin, transferrin, cortisol, and adrenocorticotropic hormone levels were unremarkable.

The patient continued to take belumosudil for treatment of GVHD. The hyperpigmentation faded slightly by a 2-month follow-up visit but persisted and was stable. She has not tried other treatments for GVHD to manage the hyperpigmentation.

Conditions known to cause diffuse bronzing of the skin include Addison disease, hemochromatosis, Cushing disease, and medication adverse events. Our patient presented with an absence of systemic symptoms, normal laboratory results, and no clinical indicators suggesting alternate causes. Given that the onset of the hyperpigmentation was 3 weeks after she started a new medication, we hypothesized that the bronzing was an adverse effect of the belumosudil—though this correlation cannot be definitively proven by this case.

The most common offending agents for drug-induced skin hyperpigmentation are nonsteroidal anti- inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, and tetracyclines.^1,2 Our patient’s medication list included the cytotoxic agent acalabrutinib, a Bruton tyrosine kinase inhibitor used for the treatment of non-Hodgkin lymphoma. It has been associated with dermatologic findings of ecchymosis, bruising, panniculitis, and cellulitis, but there are no known reports of hyperpigmentation.³ Our patient had been taking acalabrutinib for 6 months when the GVHD rash developed. At the time, she also was taking a multivitamin and lutein, biotin, and fish oil supplements, none of which have been associated with hyperpigmentation.

Polypharmacy adds a layer of difficulty in identifying the inciting cause of pigmentary change. In our case, symptoms began 3 weeks after the initiation of belumosudil. There were no cutaneous reactions observed in the ROCKstar study of belumosudil; the most common adverse events were upper respiratory tract infection, diarrhea, fatigue, nausea, increased liver enzymes, and dyspnea.^4,5 Patients on belumosudil have developed aggressive cutaneous squamous cell carcinoma.⁶ However, a search of PubMed articles indexed for MEDLINE using the search terms acalabrutinib or belumosudil with hyperpigmentation or cutaneous reaction returned no reports of these medications causing hyperpigmentation or cutaneous deposits.

Treatment of drug-induced hyperpigmentation is difficult because discontinuation of the offending agent typically confirms diagnosis, but interruption of treatment is not always possible, as in our patient. The skin changes can fade over time, but effects typically are long lasting.

Dermatologists play a key role in the identification of drug-induced skin hyperpigmentation. After endocrine or metabolic causes of skin hyperpigmentation have been ruled out, a thorough review of the patient’s medication list should be done to assess for a drug-induced cause. Treatment is limited to sun avoidance, as interruption of treatment may not be possible, and lesions typically do fade over time. These chronic skin changes can have a psychosocial effect on patients and regular follow-up is recommended.